Discovery may lead to targeted heart disease treatments
University of Guelph researchers have found the location and effect of abnormal heart proteins that can cause cardiac failure, a discovery that points to potential new ways to treat the most costly health problem in the world.
The study appears today in PLoS ONE, a peer-reviewed international journal published by the Public Library of Science.
“In order to cure heart disease, you have to understand its fundamental properties,” said study author John Dawson, a molecular and cellular biology professor.
“So we looked at variants of naturally occurring proteins that are found in people with heart disease.”
The research team included graduate students Maureen Mundia, Ryan Demers, Melissa Chow and Alexandru Perieteanu.
Heart disease and stroke is the leading cause of death in Canada, killing tens of thousands each year. Treating cardiovascular disease costs more than $20 billion a year in physician and hospital costs, lost wages and reduced productivity.
The study examined gene abnormalities for the actin protein and its role in heart failure.
As the most abundant protein in the body, actin helps in vital processes including muscle movement.
Abnormal actin genes are linked to heart diseases such as hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). HCM causes excessive thickening of the heart muscle and can lead to sudden cardiac death. Under DCM, the heart weakens and enlarges, and cannot pump blood efficiently.
Scientists had already linked HCM and DCM to 14 actin gene abnormalities. “But this is the first time that many of these variants have been studied at the molecular level,” Dawson said.
Understanding the molecular deficiencies of actin variants is a starting point for figuring out the underlying mechanisms of heart diseases, he said.
The researchers inserted human genes into insect cells to make heart muscle proteins for study. Dawson’s lab is one of the few in the world able to do this work.
They then mapped where on the abnormalities occurred and their effects. Three were in spots that resulted in problems with heart contractions; three others were in locations that affected stability and efficiency.
Symptoms of Irregular Heart Rate
The general symptoms of irregular heart rate include pounding in the chest, shortness of breath, dizziness, simple chest discomfort, fatigue and palpitations. Some people may be suffering from an irregular heart rate and not even know it. An echocardiogram, or ECG, can find out for sure whether or not someone suffering from some or all of these symptoms is experiencing an irregular heart rate.
If someone only suffers from the symptoms of irregular heart rate after exercise, an echocardiogram may not be able to detect the problem. If this is the case, an Exercise stress test may be needed to diagnose irregular heart rate and its possible cause.
Irregular Heart Rate
An irregular heart rate after exercise could be a sign of other heart conditions. A imbalance of electrolytes such as potassium or sodium could cause an irregular heart rate after exercise. Excessive smoking or caffeine consumption could also cause a postexercise arrhythmia. Also, exercise is a form of stress, and excessive exercise can cause in irregular heart rate.
Dawson hopes their work will help in developing more targeted treatments.
“Heart disease has many different forms and variants. If we can design specific therapies that address the precise mechanisms of the things going on — treat the root cause rather than the whole system — then we can improve the quality of life for people.”
Heart failure is a long-term (chronic) condition, but it can sometimes develop suddenly.
The condition may affect only the right side or only the left side of the heart. These are called right-sided heart failure or left-sided heart failure. More often, both sides of the heart are involved.
Heart failure is present when:
Your heart muscle cannot pump (eject) the blood out of the heart very well. This is called systolic heart failure.
Your heart muscles are stiff and do not fill up with blood easily. This is called diastolic heart failure.
Both of these problems mean the heart is no longer able to pump enough oxygen-rich blood out to the rest of your body, especially when you exercise or are active.
As the heart’s pumping action is lost, blood may back up in other areas of the body. Fluid builds up in the lungs, liver, gastrointestinal tract, and the arms and legs. This is called congestive heart failure.
The most common cause of heart failure is coronary artery disease (CAD), a narrowing of the small blood vessels that supply blood and oxygen to the heart.
Dawson belongs to a growing cardiovascular research group at the University of Guelph, one of few such groups worldwide studying cardiovascular disease from single molecules to animal models.
“It makes Guelph a unique place to do this research,” he said.
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John Dawson
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University of Guelph