Sphingosine-1-phosphate induced increase in tension development of aortic valve leaflets is mediated via sphingosine-1-phosphate 2 receptor

Abstract

Sphingosine-1-phosphate (S1P) has emerged as potent bioactive lipid with multiple functions in cardiovascular pathophysiology. However, nothing is known about the potential role of S1P in heart valves and about the signaling pathways involved. Accordingly cusp tissue has been shown to have contractile properties, but little is known as to which receptors mediate these effects. Here we investigated the effect of S1P on tension development of isolated strips of porcine aortic valve leaflets. Exposure to 90 mM KCl evoked a mean increase in force of contraction of 0.5±0.03 mN under control conditions without significant difference between the experimental groups. Increasing concentrations of S1P significantly enhanced force of contraction (112.6±2.3% at 1µM, 118.1±3.9% at 2µM, and 124.5±4.0% at 5µM) compared with control conditions. The S1P effect was completely blunted in the presence of S1P2 receptor inhibitor JTE-013. This is in accordance with previous results of our group showing that S1P induces contraction of valvular interstitial cells (VICs) from porcine aortic valves by signaling via S1P2, RhoA, and RhoA-associated protein kinase. In this way, S1P may contribute to regulation of tissue tension in aortic valves.