Untitled

Abstract

S100A1 and S100B are members of a family of 20 kDa Ca2+-binding homodimers that play a role in signal transduction in mammalian cells. S100A1 is the major isoform in normal heart and S100B, normally a brain protein, is induced in hypertrophic myocardium and functions as an intrinsic negative modulator of the hypertrophic response. In order to examine the function of S100A1, we first showed that, in contrast to S100B, S100A1 was downregulated in rat experimental models of myocardial hypertrophy following myocardial infarction or pressure overload. Second, in co-transfection experiments in cultured neonatal rat cardiac myocytes, S100A1 inhibited the alpha1-adrenergic activation of promoters of genes induced during the hypertrophic response including the fetal genes skeletal alpha actin (skACT), and beta-myosin heavy chain (MHC) and S100B, but not the triiodothyronine (T3) activation of the promoter of the alpha-MHC gene, that is normally expressed in adult myocardium. These results suggest that S100A1 is involved in the maintenance of the genetic program that defines normal myocardial function and that its downregulation is permissive for the induction of genes that underlie myocardial hypertrophy.

Transgenic Overexpression of the Ca2+-binding Protein S100A1 in the Heart Leads to Increased in Vivo Myocardial Contractile Performance

“…Adenoviral-mediated overexpression of S100A1 protein in cellular cardiac preparations in vitro resulted in marked increases in the rate of contraction and relaxation that was associated both with increased intracellular Ca 2ϩ transients and decreased Ca 2ϩ sensitivity of cardiac myofilaments (6). Interestingly, heart failure, a state in which S100A1 has been found to be significantly down-regulated (3,8), is characterized by impaired cardiac contractility and diminished Ca 2ϩ transients as well as increased Ca 2ϩ sensitivity of myofilaments (9 -11). In contrast to what was found in the chronically failing heart, S100A1 protein expression was found to be significantly up-regulated in compensated cardiac hypertrophy (12), suggesting that the plastic-ity of S100A1 protein expression correlates with changes in cardiac contractile state.…”

Elevated plasma S100A1 level is a risk factor for ST-segment elevation myocardial infarction and associated with post-infarction cardiac function

“…It is also proposed that S100A1 could maintain normal adult gene expression in myocardial tissue to inhibit cardiac hypertrophy. Decreased intracellular S100A1 in heart failure may unblock a fetal genetic program which initiated a hypertrophic response in damaged cardiomyocytes 48. However, previous studies mainly focused on the intracellular and tissue protein expression of S100A1, few studies revealed the changes in plasma S100A1 level in patients with post-infarction cardiac dysfunction.…”

Intracellular and Extracellular Effects of S100B in the Cardiovascular Response to Disease

“…S100A1 exhibits increased expression in compensated hypertrophy, decreased expression in human cardiomyopathy, and downregulation following experimental myocardial infarction [63, 64]. S100A1 knockout mice showed elevated systemic blood pressure, reduced endothelium-dependent vasorelaxation, and decreased survival after myocardial infarction [65, 66].…”