Discovery May Lead to Targeted Heart Disease Treatments

Canadian researchers have found the location and effects of mutations in cardiac actin that may cause heart failure.

They say that these findings could point to potential new ways to treat the most costly health problem in the Western world.

“In order to cure heart disease, you have to understand its fundamental properties,” said study author John Dawson, University of Guelph in Ontario, Canada.

The study investigated the role that the actin protein, one of the most abundant proteins in the body, plays in the development of heart failure.

Abnormal actin proteins have previously been linked to heart diseases such as hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM).

In the present study, seven known cardiac actin mutants were expressed in a baculovirus system, and their intrinsic properties studied.

Dawson et al found that the locations of mutations on the actin protein correlated with the molecular effects. Specifically, mutations in subdomain 3 affected the stability of the actin protein or affected the polymerization of actin filaments, while mutations in subdomains 1 and 4 appeared to affect protein–protein interactions.

The researchers note that these changes in the actin protein were subtle. However, they say they might reflect the late development of some HCM and DCM cases in humans.

Understanding the molecular deficiencies of actin variants is a starting point for discovering the underlying mechanisms of heart disease, commented Dawson.

He hopes that 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.”

The findings are published in the journal PLoS ONE.

By Nikki Withers