Biologic function and clinical potential of telomerase and associated proteins in cardiovascular tissue repair and regeneration.

Abstract

Telomeres comprise long tracts of double-stranded TTAGGG repeats that extend for 9-15 kb in humans. Telomere length is maintained by telomerase, a specialized ribonucleoprotein that prevents the natural ends of linear chromosomes from undergoing inappropriate repair, which could otherwise lead to deleterious chromosomal fusions. During the development of cardiovascular tissues, telomerase activity is strong but diminishes with age in adult hearts. Dysfunction of telomerase is associated with the impairment of tissue repair or regeneration in several pathologic conditions, including heart failure and infarction. Under both physiologic and pathophysiologic conditions, telomerase interacts with promyogenic nuclear transcription factors (e.g. myocardin, serum response factor) to augment the potency of cardiovascular cells during growth, survival, and differentiation. We review recent findings on the biologic function of telomerase and its potential for clinical application in cardiovascular development and repair. Understanding the roles of telomerase and its associated proteins in the functional regulation of cardiovascular cells and their progenitors may lead to new strategies for cardiovascular tissue repair and regeneration.