News | January 06, 2015

Why Do Only Some People with Hereditary Heart Disease Experience Symptoms?

Environmental stress plays key role in hypertrophic cardiomyopathy, Loyola study finds

January 6, 2015 — As many as 500,000 people in the United States have a heritable and potentially fatal heart disease called hypertrophic cardiomyopathy.

The disease can cause irregular heartbeats, heart valve problems, heart failure and, in rare cases, sudden cardiac death in young people. But some people who carry gene mutations that cause hypertrophic cardiomyopathy never experience symptoms.

A new study helps explain why. For the first time, researchers have found that in addition to gene mutations, environmental stress plays a key role in development of the disease.

The study, led by senior author Sakthivel Sadayappan, Ph.D., MBA, of Loyola University Chicago Stritch School of Medicine, is published in the Journal of Molecular and Cellular Cardiology.

Sadayappan’s study involved mice who carried mutations that cause hypertrophic cardiomyopathy. To study the effect of environmental stress, researchers performed a procedure that mimics high blood pressure. This environmental stress significantly increased three measures of hypertrophic cardiomyopathy: The hearts became heavier, the pumping ability decreased and there were lower levels of a protein that is critical for the normal functioning of the heart. The protein is called cardiac myosin binding protein-C, or cMyBP-C.

The findings suggest that carriers of hypertrophic cardiomyopathy mutations who do not yet have symptoms may be at greater risk of developing cardiomyopathy from a variety of environmental stressors, such as high blood pressure, diabetes and alcohol use. This is due to the compounding effects of stress and insufficient levels of cMyBP-C, Sadayappan and colleagues wrote.

In an accompanying editorial, Jennifer Strande, M.D., Ph.D. of the Medical College of Wisconsin, wrote that the findings were unexpected. The findings lead to the “provocative suggestion” that stress plays a role in the disease process and may help explain why only some of the carriers of gene mutations get the disease.

Sadayappan’s study was a collaboration between Loyola and Harvard Medical School. Co-authors are David Barefield, Ph.D. (first author), Mohit Kumar, M.S.; Pieter de Tombe, Ph.D. of Loyola University Chicago Stritch School of Medicine; Joshua Gorham, B.A., Jonathan Seidman, Ph.D. and Christine Seidman, M.D. of Harvard Medical School.

The study is titled “Haplionsufficiency of MYBPC3 exacerbates the development of hypertrophic cardiomyopathy in heterozygous mice” and was funded by grants from the National Heart, Lung and Blood Institute and American Heart Association.

For more information:, www.hms.har

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