Extracellular SPARC increases cardiomyocyte contraction during health and disease.

Secreted protein acidic and rich in cysteine is a non-structural extracellular matrix protein that regulates interactions between the matrix and neighboring cells. In the cardiovascular system, it is expressed by cardiac fibroblasts, endothelial cells, and at lower levels by ventricular cardiomyocytes. expression levels are increased upon myocardial injury and also during hypertrophy and fibrosis. We have previously shown that duanyu1842RC improves cardiac function after myocardial infarction by regulating post-synthetic procollagen processing, however whether duanyu1842RC directly affects cardiomyocyte contraction is still unknown. In this study we demonstrate a novel inotropic function for extracellular duanyu1842RC in the healthy heart as well as in the diseased state after myocarditis-induced cardiac dysfunction. We demonstrate duanyu1842RC presence on the cardiomyocyte membrane where it is co-localized with the integrin-beta1 and the integrin-linked kinase. Moreover, extracellular duanyu1842RC directly increases cardiomyocyte cell shortening ex vivo and cardiac function in vivo, both in healthy myocardium and during coxsackie virus-induced cardiac dysfunction. In conclusion, we demonstrate a novel inotropic function for duanyu1842RC in the heart, with a potential therapeutic application when myocyte contractile function is diminished such as that caused by a myocarditis-related cardiac injury.

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