title: Cardiomyocytes, endothelial cells and cardiac fibroblasts: S100A1's triple action in cardiovascular pathophysiology.
abstract: Over the past decade, basic and translational research delivered comprehensive evidence for the relevance of the Ca(2+)-binding protein S100A1 in cardiovascular diseases. Aberrant expression levels of S100A1 surfaced as molecular key defects, driving the pathogenesis of chronic heart failure, arterial and pulmonary hypertension, peripheral artery disease and disturbed myocardial infarction healing. Loss of intracellular S100A1 renders entire Ca(2+)-controlled networks dysfunctional, thereby leading to cardiomyocyte failure and endothelial dysfunction. Lack of S100A1 release in ischemic myocardium compromises cardiac fibroblast function, entailing impaired damage healing. This review focuses on molecular pathways and signaling cascades regulated by S100A1 in cardiomyocytes, endothelial cells and cardiac fibroblasts in order to provide an overview of our current mechanistic understanding of S100A1's action in cardiovascular pathophysiology.
authors.forename: David
authors.initials: D
authors.lastname: Rohde
authors.forename: Martin
authors.initials: M
authors.lastname: Busch
authors.forename: Anne
authors.initials: A
authors.lastname: Volkert
authors.forename: Julia
authors.initials: J
authors.lastname: Ritterhoff
authors.affiliation: 2German Centre for Cardiovascular Research (DZHK), partner site Heidelberg/Mannheim, Heidelberg University Hospital, Heidelberg University, INF 410, 69120 Heidelberg, Germany.
authors.forename: Hugo A
authors.initials: HA
authors.lastname: Katus
authors.affiliation: 3Center for Translational Medicine, Department of Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA.|4uniQure GmbH, INF 410, 69120 Heidelberg, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Peppel
authors.affiliation: 2German Centre for Cardiovascular Research (DZHK), partner site Heidelberg/Mannheim, Heidelberg University Hospital, Heidelberg University, INF 410, 69120 Heidelberg, Germany.|3Center for Translational Medicine, Department of Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA.|4uniQure GmbH, INF 410, 69120 Heidelberg, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Most
mesh_terms: D002318:Cardiovascular Diseases / Q000378:metabolism* / Q000473:pathology; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology*; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D006801:Humans; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology*; D009418:S100 Proteins / Q000378:metabolism*
chemical_list: D009418:S100 Proteins; C110294:S100A1 protein
keywords: S100A1; calcium cycling; cardiac fibroblast; endothelial cell dysfunction; gene therapy; heart failure; peripheral artery disease