Nuclear receptor corepressor 1 represses cardiac hypertrophy

VCP represses pathological cardiac hypertrophy

CIP, a cardiac Isl1-interacting protein, represses cardiomyocyte hypertrophy.

RATIONALE Mammalian heart has minimal regenerative capacity. In response to mechanical or pathological stress, the heart undergoes cardiac remodeling. Pressure and volume overload in the heart cause increased size (hypertrophic growth) of cardiomyocytes. Whereas the regulatory pathways that activate cardiac hypertrophy have been well-established, the molecular events that inhibit or repress car...

The structure of corepressor Dax-1 bound to its target nuclear receptor LRH-1.

The Dax-1 protein is an enigmatic nuclear receptor that lacks an expected DNA binding domain, yet functions as a potent corepressor of nuclear receptors. Here we report the structure of Dax-1 bound to one of its targets, liver receptor homolog 1 (LRH-1). Unexpectedly, Dax-1 binds to LRH-1 using a new module, a repressor helix built from a family conserved sequence motif, PCFXXLP. Mutations in t...

Protease-Activated Receptor-1 Contributes to Cardiac Remodeling and Hypertrophy

Background—Protease-activated receptor-1 (PAR-1) is the high-affinity receptor for the coagulation protease thrombin. It is expressed by a variety of cell types in the heart, including cardiomyocytes and cardiac fibroblasts. We have shown that tissue factor (TF) and thrombin contribute to infarct size after cardiac ischemia-reperfusion (I/R) injury. Moreover, in vitro studies have shown that PA...

Regulation of cardiac hypertrophy: the nuclear option

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