1. Extracellular SPARC increases cardiomyocyte contraction during health and disease
- Author
-
Daniel M. Johnson, Sophie Deckx, Marieke Rienks, Anna-Pia Papageorgiou, Jolanda van der Velden, Stephane Heymans, Karin R. Sipido, Paolo Carai, Elza D. van Deel, Physiology, ACS - Heart failure & arrhythmias, Promovendi CD, Cardiologie, RS: CARIM - R2.02 - Cardiomyopathy, MUMC+: MA Med Staf Spec Cardiologie (9), and RS: Carim - H02 Cardiomyopathy
- Subjects
0301 basic medicine ,Inotrope ,Male ,Physiology ,030204 cardiovascular system & hematology ,Cardiovascular Physiology ,Biochemistry ,Muscle hypertrophy ,Extracellular matrix ,ACTIVATION ,Mice ,0302 clinical medicine ,Fibrosis ,Animal Cells ,Medicine and Health Sciences ,Myocyte ,Myocytes, Cardiac ,Osteonectin ,Cells, Cultured ,CARDIAC DILATATION ,Cardiomyocytes ,Multidisciplinary ,Chemistry ,Heart ,Animal Models ,Cell biology ,APOPTOSIS ,Precipitation Techniques ,Multidisciplinary Sciences ,Myocarditis ,Experimental Organism Systems ,cardiovascular system ,Medicine ,Science & Technology - Other Topics ,Cellular Types ,Anatomy ,INFARCTION ,Research Article ,Cardiac function curve ,EXPRESSION ,VIRAL MYOCARDITIS ,Science ,OSTEOGLYCIN PREVENTS ,Muscle Tissue ,Coxsackievirus Infections ,Mouse Models ,Research and Analysis Methods ,03 medical and health sciences ,Model Organisms ,Extracellular ,medicine ,Animals ,Immunoprecipitation ,Rats, Wistar ,Protein kinase B ,Heart Failure ,Muscle Cells ,Science & Technology ,AKT ,Myocardium ,Biology and Life Sciences ,Proteins ,Cell Biology ,medicine.disease ,Myocardial Contraction ,DYSFUNCTION ,COLLAGEN ,030104 developmental biology ,Biological Tissue ,Cardiovascular Anatomy ,Animal Studies ,Collagens ,Developmental Biology - Abstract
Secreted protein acidic and rich in cysteine (SPARC) 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. SPARC expression levels are increased upon myocardial injury and also during hypertrophy and fibrosis. We have previously shown that SPARC improves cardiac function after myocardial infarction by regulating post-synthetic procollagen processing, however whether SPARC directly affects cardiomyocyte contraction is still unknown. In this study we demonstrate a novel inotropic function for extracellular SPARC in the healthy heart as well as in the diseased state after myocarditis-induced cardiac dysfunction. We demonstrate SPARC presence on the cardiomyocyte membrane where it is co-localized with the integrin-beta1 and the integrin-linked kinase. Moreover, extracellular SPARC 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 SPARC in the heart, with a potential therapeutic application when myocyte contractile function is diminished such as that caused by a myocarditis-related cardiac injury. ispartof: PLOS ONE vol:14 issue:4 ispartof: location:United States status: published
- Published
- 2019
- Full Text
- View/download PDF