Factor-Xa-induced mitogenesis and migration require sphingosine kinase activity and S1P formation in human vascular smooth muscle cells

Abstract

These data suggest that FXa induces SPHK1 expression and increases S1P formation independent of thrombin and that this involves the activation of Rho A and PKC signalling. In addition to its key function in coagulation, this direct effect of FXa on human SMC may increase cell proliferation and migration at sites of vessel injury and thereby contribute to the progression of vascular lesions.

Corticotrophin-releasing factor participates in S1PR3-dependent cPLA2 expression and cell motility in vascular smooth muscle cells

“…S1P has also been well proven to impact cell migration in VSMCs [41]. Based on our observation, Sphk1 expression and S1P synthesis were markedly increased by CRF.…”

DJ-1-mediated upregulation of serine palmitoyltransferase 2 controls vascular neointima via S1P autocrine

“…This study is, to the best of our knowledge, the first to clarify the role of the DJ-1 protein in SPL-mediated VSMC function. Furthermore, our results suggest that the control of the S1P production and secretion on VSMCs is helpful for the modulation of vascular disorders via the diminution of autocrine S1P [6].…”

Sphingosine 1-Phosphate as a Link between Blood Coagulation and Inflammation

“…Recent work from our laboratory has shown that FXa regulates transcription of SPHK1 and elevates S1P biosynthesis in human vascular smooth muscle cells (Fig. 1A, 1B) [46]. This stimulatory effect, observed in cultured cells, was seen at FXa concentrations (3 to 30 nM) which have been shown to occur during thrombus formation ex vivo [8].…”

“…Overlay (yellow) indicates a spatial association of both proteins in human atherosclerotic plaques. Modified after Böhm et al [46]. …”