Cardiovascular Disease Research Paper
1) What is molecular biology? In other words, what are molecules and how are they studied?
Molecular biology is the in depth study of life at the fundamental level of macromolecules. Macromolecules are the components that make up molecules, for example proteins or nucleic acids are components of most molecules. Molecules are two or more atoms bound together with various types of atomic bonds. They represent the smallest fundamental unit of life, basically making up our universe. Since molecular biologists study the most basic components of life, the field of research often overlaps with the study of organic chemistry and other areas of biology such as cell biology.
It is believed that the first molecules were created 15 billion years ago as a result of the big bang. The first molecules were very simple, two hydrogen atoms sticking together, but eventually supernovas and exploding stars in space created new types of atoms and more complicated molecules formed. When two hydrogen atoms bonded with an oxygen atom, the first water molecules were created. When hydrogen atoms bonded with carbon atoms, hydrocarbon molecules were formed. These hydrocarbon atoms were the basis for the formation of organic life on planet Earth. Everything on planet earth is made of molecules, from people to plants to rocks and the earth itself.
Because molecules make up everything around us, and humans themselves, it is the basis for all other sciences. All other biological sciences are built on molecular biology, especially genetics and biochemistry. Molecular biology is so closely interconnected with genetics because molecular biologists study how the biggest organic molecule, deoxyribonucleic acid, is capable of holding such valuable information. They study how deoxyribonucleic acid (DNA) interacts with other molecules and atoms to copy genetic information that leads to the creation of new molecules.
Molecular biology is a very wide field of study because molecules can be responsible for so many purposes in a living organism. Although most things are made out of molecules, molecular biologists only study the molecules making up living organisms such as plants or animals. A scientist who studies molecules in general is called a molecular scientist or molecular researcher. Molecular biologists work very closely with molecular scientists because they are all studying the same fundamental concepts. But molecular biology is much more complex than traditional molecular sciences because they have to figure out how molecules interact inside a living organism and how these interactions of molecules affect the health, appearance, or behavior of the organism.
Most molecules are too small to be seen with the naked eye, but there are a few exceptions. DNA for example, if extracted from a cell nucleus can be observed with the human eye. Most molecules however are much smaller. A glucose is just 0.5 nm in diameter. A protein is about 5 nm in diameter, a typical virus is 50 nm, a bacterium is 5,000 nm across. To put this into perspective, a typical period (.) is about 500,000 nm across! Because molecules are so small, it makes it very difficult to directly observe them, but we can study them in other ways.
Because everything is made up of molecules, it seems reasonable to assume that knowing everything you can about each specific molecule would be the first step in understanding that thing. We need to understand the individual molecules before we can understand the actions of cells or the results of chemical reactions.
One method of observing individual molecules is the method of using gold and light to observe molecules in water. A new device the size of a human hair allows scientists to detect the presence of and monitor the behavioral interactions of one specific molecule. This device was developed by Dr. Hatice Altug and her student Ronen Adato at Boston University just this past July. The device is based of a well known method of detection, the infrared absorption spectroscopy, which bounces infrared light off of molecules and detects how fast the beams vibrate. Because each type of molecule yields a unique vibration pattern, scientists can figure out which type of molecule was present. It is basically like a string instrument, the string vibrated differently depending on the length of the string. This old method worked very well in dry environments, but only if many of the same molecule were present.
The goal was to develop a system capable of targeting just one molecule in various areas, not just dry test areas. What they developed was a penny sized device made up of chambers filled with fluid. One side of the chambers are covered with tiny gold particles. The gold particles make it possible to separate the molecule of study from the surrounding liquid. The gold nanoparticles also help concentrate the beam of light down to only 1 nm. In the chamber, the beam of light is aimed at the nanoparticle, which narrows the beam. When the beam narrows, it creates a funnel like effect, trapping the target molecule and exposing it to the most intense number of photons.
This new device is far more precise than any previous method of observing molecules. It could bring better, more exact ways to measure the interaction of molecules which would be a critical step in the understanding of disease progression and treatment.
The simplest way to prove the presence of a specific molecule is to identify a product of a molecular reaction, then work backwards and figure out which molecules must have been present to get that specific result. A simple example would be if you have an unknown molecule, say oxygen, you could mix it with another molecule that you know, such as hydrogen, which would form water. Then you would know the unknown molecule was oxygen because your control element was hydrogen and your product was water so it is easy to work backwards and figure out what you started with. This is a simple example, and of course molecular biologists would be working with huge and more complex reactions, but this is the basic method that is used. Of course, this method is long and tedious, so new efficient methods need to be developed in order to identify the presence of specific molecules faster and easier.
2) What goes wrong with or goes on with molecules in cardiovascular disease?
Cardiovascular disease refers to any disease or damage that affects the heart, lungs, or circulatory system (veins and arteries). Cardiovascular disease, also called heart disease, has a very wide range of symptoms and causes. Most cardiovascular diseases are associated with a condition called atherosclerosis, which is a condition that develops if plaque builds up on the walls of the vessels and arteries. Buildup of plaque in the arteries makes it harder for blood to easily pass through. If a blood clot were to form in the arteries of someone who had a lot of plaque build up, the clot could get stuck in an artery, stopping blood flow to that area altogether. If the clot gets stuck in the heart, the person will suffer a heart attack and if the clot gets stuck in the brain, a stroke will result.
Heart attacks are the most common result of atherosclerosis, each year about 715,000 people suffer from one and almost 600,000 people die as a result. Another common cardiovascular problem is asthma, affecting about one in twelve people in the United States. In 2008, almost 17.3 million people died from cardiovascular diseases, making up 30% of world deaths. Cardiovascular diseases are defined as any disease or damage to the heart, lungs, veins, or vessels.
There are both genetic and environmental causes that can lead to cardiovascular disease. One devastating environmental cause for cardiovascular problems is smoking. Smoking increases the amount of carbon monoxide and nicotine in your system. Carbon monoxide molecules bind with haemoglobin molecules in the bloodstream. Haemoglobin is responsible for carrying oxygen from lungs to tissues, so if carbon monoxide bonds with it, the tissues may not receive enough oxygen. Smoking can also lead to an increase in blood pressure because of the amount of thiocyanate molecules in the blood stream is too high. Too much thiocyanate in the blood makes the inside of the veins and arteries sticky, allowing cholesterol or plaque to build up more easily on the walls.
Another environmental cause for cardiovascular disease is lack of proper nutrition. People who eat a high amount of cholesterol in their diets are more likely to develop cardiovascular diseases. People who are overweight are much more likely to suffer from cardiovascular problems because blood lipid levels affect how well blood pressure is monitored. People who are overweight are at much higher risk for hypertension, or high blood pressure, which can lead to constriction of the arteries as blood is not able to pass through and be circulated as it should.
While most sufferers of heart attack or hypertension are overweight or smoke, there are numerous cardiovascular problems that are caused by genetic mutations. One genetic mutation is a mutation in the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene. This gene is responsible for making a key protein involved in regulation of the low-density lipoprotein receptors or LDLR. LDLRs are proteins found on the surface of cells. The amount of LDLR on the surface of the cells of the liver determines how quickly cholesterol is absorbed out of the bloodstream. Someone who has a defect in the PCSK9 gene will not have the proper amount of LDLR on their liver, so cholesterol will not be absorbed properly. When cholesterol is not properly regulated in the bloodstream, it can build up in vessels causing heart attack or stroke.
Another cardiovascular condition associated with genetics is congenital heart disease. Congenital heart disease is a heart problem that appears at birth. The problem is caused during fetal development if heart does not properly develop. Five to six percent of babies with congenital heart disease have an abnormality in their chromosomes. Three to seven percent have single gene mutations caused by environmental factors. In 85 to 90 percent of cases, there is no exact cause for the mutation and those cases are considered to have multifactorial inheritance. Multifactorial inheritance means that the mutation is caused by a faulty combination of genes from each parent, or a mixture of environmental and genetic causes.
There are many genetic mutations that can lead to problems with the cardiovascular system. One inherited disease is marfan syndrome, an abnormal formation of the protein called fibrillin. The FBN1 gene is responsible for the regulation of the fibrillin protein. Marfan syndrome is a genetic mutation in the FBN1 gene. It is a dominant mutation, meaning that if either of the parents have the mutation the child will suffer from marfan and they will pass it down to their children.
Another good example of how molecules can affect the cardiovascular system is asthma. Asthma is a chronic inflammation of the respiratory tract and affects one in every 12 people in the US. We know that asthma can be caused by various environmental factors, such as dust or allergens, but asthma can also be caused by mutation in immune molecules. Hyperreactive Th cells are formed as part of the immune system and they are important in the genetic cause of asthma. New findings show that a gene regulating molecule (a molecule that makes sure that other molecules are not mutated) called IRF4 can be important in the development of asthma. Changes in the IRF4 molecule can cause it to do it’s job incorrectly. If it starts to think that some molecules are mutated, even if they are not, it will remove them from the system. In people with asthma, the IRF4 molecule interferes with the regulation of Th9 cells, and are therefore not able to produce enough IL-9 molecules. Changes in the amount of IL-9 molecules can cause asthma symptoms.
While most cardiovascular diseases have external as well as genetic causes, they all have some similarities. Most cardiovascular problems are connected to the buildup of excess cholesterol in the form of plaque in the vessels. This buildup can be caused by problems with the proprotein convertase subtilisin/kexin type 9 gene, which regulates the low-density lipoprotein receptors. Low-density lipoprotein receptors affect how quickly cholesterol is cleaned out of the bloodstream. Other causes of cardiovascular disease are environmental causes such as smoking or problems during fetal development.
3) What research is going on to understand the disease in terms of molecules?
Due to the increased number of deaths due to cardiovascular diseases in recent years, scientists have begun new groundbreaking studies on the issue. Scientists know that most cardiovascular problems are caused if the body is not able to properly regulate low density lipoprotein receptors in the bloodstream because excess low density lipoproteins in the blood cause blockage in vessels and arteries. Blockage in the arteries affects the effectiveness of circulation, if not enough oxygen molecules can get to certain tissues, the tissues will die. Scientists also know that conditions such as high blood pressure can also make the problem worse. Think of it like a hallway at school, all of the kids stand in groups in the middle of the hallway talking. The groups represent excess low density lipoproteins. Shen there are too many of them, it is hard for other students, or oxygen molecules, to get through. An increase in blood pressure, or more students in the hallway will also make it more difficult for oxygen molecules to find their way to the tissues, or classrooms.
Scientists can tell that certain people may be prone to cardiovascular problems, but they do not know exactly why. They know that people who are overweight tend to be at a higher risk for high blood pressure, or hypertension, because these people tend to eat a diet based mostly on cholesterol. Cholesterol, when ingested, is absorbed as low density lipoproteins. This increase in low density lipoproteins, mixed with the added risk for coronary artery disease leaves overweight people at a much higher risk for heart attacks. Coronary artery disease is a disease in which the arteries are coated with a waxy plaque. The buildup stops the flow of oxygen molecules to the heart muscle, causing chest pain or heart attack.
In recent years, new studies have been emerging that are trying to use molecular imaging to diagnose cardiovascular problems early so that they can be cured more easily. Molecular imaging is a complex detection method that uses a signal detection compound and corresponding software to be able to identify a specific molecular target. The molecules studied would be the ones that are caused by the disease, for example in cardiovascular medicine, they would target low density lipoprotein. It is possible to study deoxyribonucleic acid, but it is more challenging because of its inaccessibility (it is trapped in the cell nucleus). Molecular imaging is still in development, but it has many possible uses and applications in the field of medicine and genomics.
If scientists can detect the presence of specific molecules, they can diagnose a problem before it even becomes a problem. For example if low density lipoproteins can be detected in the blood before traditional symptoms become evident, the patient could be prescribed a blood pressure lowering medication or a cholesterol lowering drug. Although molecular imaging detection methods are fairly new, the business is receiving a lot of attention and funding from the medical community.
4) What current research is going on for therapies and cures for cardiovascular disease? How do they connect with molecules?
Currently, the most successful methods of identifying and curing disease is to connect patient care with scientists directly. This allows scientists to observe and study patients directly, and not have to depend on secondary sources to relay information, which risks information being omitted or lost. Medical school hospitals or teaching hospitals are one of the leading developments in the way we understand and cure diseases. Teaching hospitals not only allows students to have a hands on way of learning, but they also attract the attention of scientists and specialists in certain areas. Teaching hospitals often are the first places experimental procedures are done, and they are often the place where many medical breakthroughs happen. In recent years, many institutes have had a strong focus on cardiovascular diseases because of the nation wide epidemic. Some institutes, such as the Scripps Institute or Gladstone Institute have opened up special departments for cardiovascular related diseases and are working to learn more about the causes of the disease so more lives can be saved.
Stalin drugs, first marketed in 1987, were a huge breakthrough in managing heart disease. This medication works by inhibiting the HMG-CoA reductase enzyme. In the liver, the HMG-CoA reductase enzyme controls production of cholesterol. The molecules from the medication are absorbed by the body and replace the HMG-CoA in the liver, which slows down the production of cholesterol. Other molecules in the liver cells sense the decrease in production of cholesterol and respond by creating a new protein. This new protein increases the production of low density lipoprotein (LDL, bad cholesterol) receptors. The purpose of these LDL receptors is to be released into the bloodstream and bind with low density lipoproteins (LDL) and very low density lipoproteins (VLDL). When low density lipoproteins are binded with low density lipoprotein receptors, they are able to be digested by the liver.
If stalin drugs don’t solve the problem, there are plenty of new surgical options that can solve lung or heart problems caused by changes in cholesterol levels. One of the most common is the coronary artery bypass graft surgery. This surgery can stop the progression of heart failure if the cause of the heart failure is lack of oxygen to the heart due to blocked arteries. Without oxygen rich blood, the heart cannot pump. This surgery uses a blood vessel graft (tissue taken from one part of the body and put into another), usually taken from the patient's arm or leg, to form a new pathway around a blocked artery in the heart. In recent years, this procedure has been intensely studied, and adjustments have been made to the procedure to decrease mortality rates.
Another option to fix heart failure, or partial heart failure, is a valve surgery. If heart failure is bad, the changes in the left ventricle can cause the papillary muscle to stretch or tear. The papillary muscle is responsible for making sure blood only flows in one direction, if it gets weak the valves start to leak. Valve repair surgery usually reshapes the muscle and adds an artificial ring to support the valve. This method has also been studied and researched because of the possible complications. Recent studies figured out a way to stabilize the valve and muscles without replacing it altogether.
Aneurysm repair surgery is a method to remove scars on the left ventricle caused by heart attacks. Unlike typical skin scars, scars on the heart become thin, bulge, risk bursting with the heart beat. Scared areas are called aneurysm. In a typical aneurysm repair, the scarred parts of the heart are removed and the remaining tissue is reattached, in extreme cases a patch might be placed over the area to reduce stretching.
A very new method of helping patients with heart failure is a left ventricular assist device, or LVDA. The device is often used as a temporary, possibly life saving, option if they do not qualify for a full heart transplant. Other patients keep the device in place for the rest of their lives. There are many types of LVDAs, and there has been a lot of modifications made to the device as well. A new type of LVDA contains an artificial heart pump which connects to a battery pack outside of the body. Other LVDA’s include devices that administer cholesterol lowering medication. The molecules in the cholesterol lowering medication bond with liver cells, and stop the creation of low density lipoproteins. The molecules in the drug also aid the production of low density lipoprotein receptors, which bond to low density lipoproteins to allow them to be absorbed by the body.
The most extreme surgical method to fix heart failure caused by buildup of cholesterol molecules in the arteries is a full heart transplant. Usually recommended only as a last resort, patients weight for a donor heart that matches certain criteria such as age, size, or blood type. The procedure is extremely long and complicated, they usually take between 4 to 12 hours. Organ transplants have been a relatively new development in the medical world. The first successful human heart transplant took place on December 3rd, 1967 by Dr. Christian Bernard. The method he used was groundbreaking for the time, now about 2,000 heart transplants are performed every year in just the United States, but at any one time nearly 3,000 people are on the heart transplant list.
In the last 50 or so years, the United States has seen a huge rise in the number of people affected with cardiovascular related illnesses. Most scientists correlate the surprising increase in this disease with the increase in obesity. There is a lot of research going on to try to figure out causes for this obesity epidemic. Some scientists believe the rise in obesity directly connects to the rise in cardiovascular diseases, but others debate that there is no definitive research proving their connection. Most doctors believe that obesity is one factor in the bodies inability to properly absorb cholesterol, which leads to plaque buildup in the arteries. Most scientists and doctors also agree that buildup of plaque in the vessels is a major cause of cardiovascular problems, as blood cannot circulate properly.
5) Who can you contact that is conducting this research to interview?
Coriell Institute for Medical Research
403 Haddon Avenue, Camden NJ 08103
Phone: (856) 966 7377
Fax: (856) 964 0254
The Scripps Research Institute
10550 North Torrey Pines Road, La Jolla CA 92037
Fax: (858) 784 208
Cardiovascular Research Institute
3500 Camp Bowie Blvd. Fort Worth TX 76107
Gladstone Institutes - Department of ‘Science of Overcoming Disease’
1650 Owens Street, San Francisco CA
Phone: (415) 734 2000
Cardiovascular Specialists, P.A.
Lewisville Office Phone (972) 4341988
Denton Office Phone (940) 320 2188
Flower Mound Office Phone (972) 874 2042
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Molecular biology is the in depth study of life at the fundamental level of macromolecules. Macromolecules are the components that make up molecules, for example proteins or nucleic acids are components of most molecules. Molecules are two or more atoms bound together with various types of atomic bonds. They represent the smallest fundamental unit of life, basically making up our universe. Since molecular biologists study the most basic components of life, the field of research often overlaps with the study of organic chemistry and other areas of biology such as cell biology.
It is believed that the first molecules were created 15 billion years ago as a result of the big bang. The first molecules were very simple, two hydrogen atoms sticking together, but eventually supernovas and exploding stars in space created new types of atoms and more complicated molecules formed. When two hydrogen atoms bonded with an oxygen atom, the first water molecules were created. When hydrogen atoms bonded with carbon atoms, hydrocarbon molecules were formed. These hydrocarbon atoms were the basis for the formation of organic life on planet Earth. Everything on planet earth is made of molecules, from people to plants to rocks and the earth itself.
Because molecules make up everything around us, and humans themselves, it is the basis for all other sciences. All other biological sciences are built on molecular biology, especially genetics and biochemistry. Molecular biology is so closely interconnected with genetics because molecular biologists study how the biggest organic molecule, deoxyribonucleic acid, is capable of holding such valuable information. They study how deoxyribonucleic acid (DNA) interacts with other molecules and atoms to copy genetic information that leads to the creation of new molecules.
Molecular biology is a very wide field of study because molecules can be responsible for so many purposes in a living organism. Although most things are made out of molecules, molecular biologists only study the molecules making up living organisms such as plants or animals. A scientist who studies molecules in general is called a molecular scientist or molecular researcher. Molecular biologists work very closely with molecular scientists because they are all studying the same fundamental concepts. But molecular biology is much more complex than traditional molecular sciences because they have to figure out how molecules interact inside a living organism and how these interactions of molecules affect the health, appearance, or behavior of the organism.
Most molecules are too small to be seen with the naked eye, but there are a few exceptions. DNA for example, if extracted from a cell nucleus can be observed with the human eye. Most molecules however are much smaller. A glucose is just 0.5 nm in diameter. A protein is about 5 nm in diameter, a typical virus is 50 nm, a bacterium is 5,000 nm across. To put this into perspective, a typical period (.) is about 500,000 nm across! Because molecules are so small, it makes it very difficult to directly observe them, but we can study them in other ways.
Because everything is made up of molecules, it seems reasonable to assume that knowing everything you can about each specific molecule would be the first step in understanding that thing. We need to understand the individual molecules before we can understand the actions of cells or the results of chemical reactions.
One method of observing individual molecules is the method of using gold and light to observe molecules in water. A new device the size of a human hair allows scientists to detect the presence of and monitor the behavioral interactions of one specific molecule. This device was developed by Dr. Hatice Altug and her student Ronen Adato at Boston University just this past July. The device is based of a well known method of detection, the infrared absorption spectroscopy, which bounces infrared light off of molecules and detects how fast the beams vibrate. Because each type of molecule yields a unique vibration pattern, scientists can figure out which type of molecule was present. It is basically like a string instrument, the string vibrated differently depending on the length of the string. This old method worked very well in dry environments, but only if many of the same molecule were present.
The goal was to develop a system capable of targeting just one molecule in various areas, not just dry test areas. What they developed was a penny sized device made up of chambers filled with fluid. One side of the chambers are covered with tiny gold particles. The gold particles make it possible to separate the molecule of study from the surrounding liquid. The gold nanoparticles also help concentrate the beam of light down to only 1 nm. In the chamber, the beam of light is aimed at the nanoparticle, which narrows the beam. When the beam narrows, it creates a funnel like effect, trapping the target molecule and exposing it to the most intense number of photons.
This new device is far more precise than any previous method of observing molecules. It could bring better, more exact ways to measure the interaction of molecules which would be a critical step in the understanding of disease progression and treatment.
The simplest way to prove the presence of a specific molecule is to identify a product of a molecular reaction, then work backwards and figure out which molecules must have been present to get that specific result. A simple example would be if you have an unknown molecule, say oxygen, you could mix it with another molecule that you know, such as hydrogen, which would form water. Then you would know the unknown molecule was oxygen because your control element was hydrogen and your product was water so it is easy to work backwards and figure out what you started with. This is a simple example, and of course molecular biologists would be working with huge and more complex reactions, but this is the basic method that is used. Of course, this method is long and tedious, so new efficient methods need to be developed in order to identify the presence of specific molecules faster and easier.
2) What goes wrong with or goes on with molecules in cardiovascular disease?
Cardiovascular disease refers to any disease or damage that affects the heart, lungs, or circulatory system (veins and arteries). Cardiovascular disease, also called heart disease, has a very wide range of symptoms and causes. Most cardiovascular diseases are associated with a condition called atherosclerosis, which is a condition that develops if plaque builds up on the walls of the vessels and arteries. Buildup of plaque in the arteries makes it harder for blood to easily pass through. If a blood clot were to form in the arteries of someone who had a lot of plaque build up, the clot could get stuck in an artery, stopping blood flow to that area altogether. If the clot gets stuck in the heart, the person will suffer a heart attack and if the clot gets stuck in the brain, a stroke will result.
Heart attacks are the most common result of atherosclerosis, each year about 715,000 people suffer from one and almost 600,000 people die as a result. Another common cardiovascular problem is asthma, affecting about one in twelve people in the United States. In 2008, almost 17.3 million people died from cardiovascular diseases, making up 30% of world deaths. Cardiovascular diseases are defined as any disease or damage to the heart, lungs, veins, or vessels.
There are both genetic and environmental causes that can lead to cardiovascular disease. One devastating environmental cause for cardiovascular problems is smoking. Smoking increases the amount of carbon monoxide and nicotine in your system. Carbon monoxide molecules bind with haemoglobin molecules in the bloodstream. Haemoglobin is responsible for carrying oxygen from lungs to tissues, so if carbon monoxide bonds with it, the tissues may not receive enough oxygen. Smoking can also lead to an increase in blood pressure because of the amount of thiocyanate molecules in the blood stream is too high. Too much thiocyanate in the blood makes the inside of the veins and arteries sticky, allowing cholesterol or plaque to build up more easily on the walls.
Another environmental cause for cardiovascular disease is lack of proper nutrition. People who eat a high amount of cholesterol in their diets are more likely to develop cardiovascular diseases. People who are overweight are much more likely to suffer from cardiovascular problems because blood lipid levels affect how well blood pressure is monitored. People who are overweight are at much higher risk for hypertension, or high blood pressure, which can lead to constriction of the arteries as blood is not able to pass through and be circulated as it should.
While most sufferers of heart attack or hypertension are overweight or smoke, there are numerous cardiovascular problems that are caused by genetic mutations. One genetic mutation is a mutation in the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene. This gene is responsible for making a key protein involved in regulation of the low-density lipoprotein receptors or LDLR. LDLRs are proteins found on the surface of cells. The amount of LDLR on the surface of the cells of the liver determines how quickly cholesterol is absorbed out of the bloodstream. Someone who has a defect in the PCSK9 gene will not have the proper amount of LDLR on their liver, so cholesterol will not be absorbed properly. When cholesterol is not properly regulated in the bloodstream, it can build up in vessels causing heart attack or stroke.
Another cardiovascular condition associated with genetics is congenital heart disease. Congenital heart disease is a heart problem that appears at birth. The problem is caused during fetal development if heart does not properly develop. Five to six percent of babies with congenital heart disease have an abnormality in their chromosomes. Three to seven percent have single gene mutations caused by environmental factors. In 85 to 90 percent of cases, there is no exact cause for the mutation and those cases are considered to have multifactorial inheritance. Multifactorial inheritance means that the mutation is caused by a faulty combination of genes from each parent, or a mixture of environmental and genetic causes.
There are many genetic mutations that can lead to problems with the cardiovascular system. One inherited disease is marfan syndrome, an abnormal formation of the protein called fibrillin. The FBN1 gene is responsible for the regulation of the fibrillin protein. Marfan syndrome is a genetic mutation in the FBN1 gene. It is a dominant mutation, meaning that if either of the parents have the mutation the child will suffer from marfan and they will pass it down to their children.
Another good example of how molecules can affect the cardiovascular system is asthma. Asthma is a chronic inflammation of the respiratory tract and affects one in every 12 people in the US. We know that asthma can be caused by various environmental factors, such as dust or allergens, but asthma can also be caused by mutation in immune molecules. Hyperreactive Th cells are formed as part of the immune system and they are important in the genetic cause of asthma. New findings show that a gene regulating molecule (a molecule that makes sure that other molecules are not mutated) called IRF4 can be important in the development of asthma. Changes in the IRF4 molecule can cause it to do it’s job incorrectly. If it starts to think that some molecules are mutated, even if they are not, it will remove them from the system. In people with asthma, the IRF4 molecule interferes with the regulation of Th9 cells, and are therefore not able to produce enough IL-9 molecules. Changes in the amount of IL-9 molecules can cause asthma symptoms.
While most cardiovascular diseases have external as well as genetic causes, they all have some similarities. Most cardiovascular problems are connected to the buildup of excess cholesterol in the form of plaque in the vessels. This buildup can be caused by problems with the proprotein convertase subtilisin/kexin type 9 gene, which regulates the low-density lipoprotein receptors. Low-density lipoprotein receptors affect how quickly cholesterol is cleaned out of the bloodstream. Other causes of cardiovascular disease are environmental causes such as smoking or problems during fetal development.
3) What research is going on to understand the disease in terms of molecules?
Due to the increased number of deaths due to cardiovascular diseases in recent years, scientists have begun new groundbreaking studies on the issue. Scientists know that most cardiovascular problems are caused if the body is not able to properly regulate low density lipoprotein receptors in the bloodstream because excess low density lipoproteins in the blood cause blockage in vessels and arteries. Blockage in the arteries affects the effectiveness of circulation, if not enough oxygen molecules can get to certain tissues, the tissues will die. Scientists also know that conditions such as high blood pressure can also make the problem worse. Think of it like a hallway at school, all of the kids stand in groups in the middle of the hallway talking. The groups represent excess low density lipoproteins. Shen there are too many of them, it is hard for other students, or oxygen molecules, to get through. An increase in blood pressure, or more students in the hallway will also make it more difficult for oxygen molecules to find their way to the tissues, or classrooms.
Scientists can tell that certain people may be prone to cardiovascular problems, but they do not know exactly why. They know that people who are overweight tend to be at a higher risk for high blood pressure, or hypertension, because these people tend to eat a diet based mostly on cholesterol. Cholesterol, when ingested, is absorbed as low density lipoproteins. This increase in low density lipoproteins, mixed with the added risk for coronary artery disease leaves overweight people at a much higher risk for heart attacks. Coronary artery disease is a disease in which the arteries are coated with a waxy plaque. The buildup stops the flow of oxygen molecules to the heart muscle, causing chest pain or heart attack.
In recent years, new studies have been emerging that are trying to use molecular imaging to diagnose cardiovascular problems early so that they can be cured more easily. Molecular imaging is a complex detection method that uses a signal detection compound and corresponding software to be able to identify a specific molecular target. The molecules studied would be the ones that are caused by the disease, for example in cardiovascular medicine, they would target low density lipoprotein. It is possible to study deoxyribonucleic acid, but it is more challenging because of its inaccessibility (it is trapped in the cell nucleus). Molecular imaging is still in development, but it has many possible uses and applications in the field of medicine and genomics.
If scientists can detect the presence of specific molecules, they can diagnose a problem before it even becomes a problem. For example if low density lipoproteins can be detected in the blood before traditional symptoms become evident, the patient could be prescribed a blood pressure lowering medication or a cholesterol lowering drug. Although molecular imaging detection methods are fairly new, the business is receiving a lot of attention and funding from the medical community.
4) What current research is going on for therapies and cures for cardiovascular disease? How do they connect with molecules?
Currently, the most successful methods of identifying and curing disease is to connect patient care with scientists directly. This allows scientists to observe and study patients directly, and not have to depend on secondary sources to relay information, which risks information being omitted or lost. Medical school hospitals or teaching hospitals are one of the leading developments in the way we understand and cure diseases. Teaching hospitals not only allows students to have a hands on way of learning, but they also attract the attention of scientists and specialists in certain areas. Teaching hospitals often are the first places experimental procedures are done, and they are often the place where many medical breakthroughs happen. In recent years, many institutes have had a strong focus on cardiovascular diseases because of the nation wide epidemic. Some institutes, such as the Scripps Institute or Gladstone Institute have opened up special departments for cardiovascular related diseases and are working to learn more about the causes of the disease so more lives can be saved.
Stalin drugs, first marketed in 1987, were a huge breakthrough in managing heart disease. This medication works by inhibiting the HMG-CoA reductase enzyme. In the liver, the HMG-CoA reductase enzyme controls production of cholesterol. The molecules from the medication are absorbed by the body and replace the HMG-CoA in the liver, which slows down the production of cholesterol. Other molecules in the liver cells sense the decrease in production of cholesterol and respond by creating a new protein. This new protein increases the production of low density lipoprotein (LDL, bad cholesterol) receptors. The purpose of these LDL receptors is to be released into the bloodstream and bind with low density lipoproteins (LDL) and very low density lipoproteins (VLDL). When low density lipoproteins are binded with low density lipoprotein receptors, they are able to be digested by the liver.
If stalin drugs don’t solve the problem, there are plenty of new surgical options that can solve lung or heart problems caused by changes in cholesterol levels. One of the most common is the coronary artery bypass graft surgery. This surgery can stop the progression of heart failure if the cause of the heart failure is lack of oxygen to the heart due to blocked arteries. Without oxygen rich blood, the heart cannot pump. This surgery uses a blood vessel graft (tissue taken from one part of the body and put into another), usually taken from the patient's arm or leg, to form a new pathway around a blocked artery in the heart. In recent years, this procedure has been intensely studied, and adjustments have been made to the procedure to decrease mortality rates.
Another option to fix heart failure, or partial heart failure, is a valve surgery. If heart failure is bad, the changes in the left ventricle can cause the papillary muscle to stretch or tear. The papillary muscle is responsible for making sure blood only flows in one direction, if it gets weak the valves start to leak. Valve repair surgery usually reshapes the muscle and adds an artificial ring to support the valve. This method has also been studied and researched because of the possible complications. Recent studies figured out a way to stabilize the valve and muscles without replacing it altogether.
Aneurysm repair surgery is a method to remove scars on the left ventricle caused by heart attacks. Unlike typical skin scars, scars on the heart become thin, bulge, risk bursting with the heart beat. Scared areas are called aneurysm. In a typical aneurysm repair, the scarred parts of the heart are removed and the remaining tissue is reattached, in extreme cases a patch might be placed over the area to reduce stretching.
A very new method of helping patients with heart failure is a left ventricular assist device, or LVDA. The device is often used as a temporary, possibly life saving, option if they do not qualify for a full heart transplant. Other patients keep the device in place for the rest of their lives. There are many types of LVDAs, and there has been a lot of modifications made to the device as well. A new type of LVDA contains an artificial heart pump which connects to a battery pack outside of the body. Other LVDA’s include devices that administer cholesterol lowering medication. The molecules in the cholesterol lowering medication bond with liver cells, and stop the creation of low density lipoproteins. The molecules in the drug also aid the production of low density lipoprotein receptors, which bond to low density lipoproteins to allow them to be absorbed by the body.
The most extreme surgical method to fix heart failure caused by buildup of cholesterol molecules in the arteries is a full heart transplant. Usually recommended only as a last resort, patients weight for a donor heart that matches certain criteria such as age, size, or blood type. The procedure is extremely long and complicated, they usually take between 4 to 12 hours. Organ transplants have been a relatively new development in the medical world. The first successful human heart transplant took place on December 3rd, 1967 by Dr. Christian Bernard. The method he used was groundbreaking for the time, now about 2,000 heart transplants are performed every year in just the United States, but at any one time nearly 3,000 people are on the heart transplant list.
In the last 50 or so years, the United States has seen a huge rise in the number of people affected with cardiovascular related illnesses. Most scientists correlate the surprising increase in this disease with the increase in obesity. There is a lot of research going on to try to figure out causes for this obesity epidemic. Some scientists believe the rise in obesity directly connects to the rise in cardiovascular diseases, but others debate that there is no definitive research proving their connection. Most doctors believe that obesity is one factor in the bodies inability to properly absorb cholesterol, which leads to plaque buildup in the arteries. Most scientists and doctors also agree that buildup of plaque in the vessels is a major cause of cardiovascular problems, as blood cannot circulate properly.
5) Who can you contact that is conducting this research to interview?
Coriell Institute for Medical Research
403 Haddon Avenue, Camden NJ 08103
Phone: (856) 966 7377
Fax: (856) 964 0254
The Scripps Research Institute
10550 North Torrey Pines Road, La Jolla CA 92037
Fax: (858) 784 208
Cardiovascular Research Institute
3500 Camp Bowie Blvd. Fort Worth TX 76107
Gladstone Institutes - Department of ‘Science of Overcoming Disease’
1650 Owens Street, San Francisco CA
Phone: (415) 734 2000
Cardiovascular Specialists, P.A.
Lewisville Office Phone (972) 4341988
Denton Office Phone (940) 320 2188
Flower Mound Office Phone (972) 874 2042
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