April 6, 2015

New player in heart cell growth

Vanderbilt researchers have identified a new protein involved in heart cell growth, which could improve understanding of pathologic cardiac hypertrophy.

Pathologic cardiac hypertrophy – thickening of the heart muscle in response to stresses including hypertension, ischemia and chronic neurohormonal activation – can result in heart failure if left untreated. Protein signaling complexes in the sarcomere (the basic contractile unit of muscle) have been shown to induce pro-growth genes and cause hypertrophy.

Chee Lim, Ph.D., and colleagues examined the role of the protein ANKRD1 (ankyrin repeat domain 1) in hypertrophic signaling. They found that ANKRD1 is part of a sarcomeric signaling complex that includes known regulators of cardiac hypertrophy. Phenylephrine (PE, a hypertrophic agonist) activated the ANKRD1 complex, which then translocated to the nucleus to induce hypertrophy. Elimination of the ANKRD1 gene in mice prevented PE-induced activation of the complex, nuclear translocation and hypertrophy.

The study, published in Cardiovascular Research, reveals a novel role for ANKRD1 in PE-induced hypertrophic cell signaling. Understanding the signaling mechanisms that control pathologic cardiac hypertrophy may lead to more effective therapeutic strategies tailored to specific forms of the disease.

This research was supported in part by grants from the National Institutes of Health (DK065656, HL095813) and the Department of Veterans Affairs.

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