S100A1: a novel inotropic regulator of cardiac performance. Transition from molecular physiology to pathophysiological relevance.
Here we review the considerable body of evidence that has accumulated to support the notion of S100A1, a cardiac-specific Ca(2+)-sensor protein of the EF-hand type, as a physiological regulator of excitation-contraction coupling and inotropic reserve mechanisms in the mammalian heart. In particular, molecular mechanisms will be discussed conveying the Ca(2+)-dependent inotropic actions of S100A1 protein in cardiomyocytes occurring independently of beta-adrenergic signaling. Moreover, we will shed light on the molecular structure-function relationship of S100A1 with its cardiac target proteins at the sarcoplasmic reticulum, the sarcomere, and the mitochondria. Furthermore, pathophysiological consequences of disturbed S100A1 protein expression on altered Ca(2+) handling and intertwined systems in failing myocardium will be highlighted. Subsequently, therapeutic options by means of genetic manipulation of cardiac S100A1 expression will be discussed, aiming to complete our current understanding of the role of S100A1 in diseased myocardium.
Most
Patrick
P
Center for Translational Medicine, Laboratory for Cardiac Stem Cell and Gene Therapy, Department of Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA. patrick.most@jefferson.edu
Remppis
Andrew
A
Pleger
Sven T
ST
Katus
Hugo A
HA
Koch
Walter J
WJ
D000818:Animals; D015316:Genetic Therapy; D006333:Heart Failure / Q000503:physiopathology* / Q000628:therapy*; D006801:Humans; D009200:Myocardial Contraction / Q000502:physiology*; D009418:S100 Proteins / Q000737:chemistry / Q000502:physiology*
D009418:S100 Proteins; C110294:S100A1 protein