Cavin-2 Deficiency Attenuates Cardiac Fibrosis and Dysfunction in Pressure-overloaded Hearts

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Received date
24 December 2018
Accepted date
24 December 2018

Best Abstract Award – First prize
Topic: Heart Failure (Basic), Molecular Cardiology


Heart failure (HF) is a debilitating disease associated with high morbidity and mortality. The high mortality rate reflects inadequacy of modern therapy and calls for new mechanistic treatments. A major cause of HF is the adverse tissue remodelling with fibrosis. Excessive extracellular matrix (ECM) turnover is involved in poor outcome. Trans-differentiation of fibroblasts into activated myofibroblasts is a defining feature of fibrosis. Myofibroblasts express alpha-smooth muscle actin and secrete ECM proteins. Previous report showed that the cavin family gene is involved in cardiac function. However, the role of Cavin-2 in cardiac fibrosis and cardiac function remains unknown.

Methods and Results

To examine the role of Cavin-2 in cardiac function, transverse aortic constriction (TAC) was performed on wild type (WT) mice and Cavin-2-/- mice. Four weeks after TAC procedure, left ventricular fractional shortening was significantly preserved in Cavin-2-/- mice. In addition, the fibrosis area was significantly attenuated in Cavin-2-/- mice. Moreover, mRNA expression of fibrosis genes was attenuated in the hearts of Cavin-2-/- mice four weeks after TAC. In in vitro study, we isolated mouse embryonic fibroblasts (MEFs) from Cavin-2-/- mice and WT mice. Western blotting showed that alpha-smooth muscle actin protein level was decreased in TGF-alpha-1 stimulated MEFs derived from Cavin-2-/- mice. Furthermore, mRNA expression of fibrosis genes was attenuated in MEFs derived from Cavin-2-/- mice.


Our observations suggest that Cavin-2 contributes to the development of cardiac fibrosis and systolic dysfunction with the differentiation of fibroblasts into myofibroblasts. Cavin-2 may be a novel therapeutic target for cardiac fibrosis.