Simvastatin induces heat shock factor 1 in vascular endothelial cells

Atorvastatin prevents hypoxia-induced inhibition of endothelial nitric oxide synthase expression but does not affect heme oxygenase-1 in human microvascular endothelial cells

“…The effect of simvastatin was concentration dependent, and although the highest expression was attained at 10 μM, already at 1 μM of simvastatin HO-1 was induced. On the other hand Uchiyama et al reported recently that 500 nM simvastatin enhanced HO-1 in human aortic endothelial cells, although the effect was moderate and no data on HO activity were shown [14].…”

Unraveling Pleiotropic Effects Of Statins

“…25 However, there are a few inconsistencies. Fu et al, 23 together with others, 26,27 show that statin decrease HSP-70 and -90, whereas Uchiyama and colleagues 22,25 show an increase of these HSPs. This discrepancy between the observations, however, does not alter the conclusion that statins (via either decreased or increased levels of HSPs) upregulate HSF-1-mediated TM expression.…”

“…28 Zhao et al 29 provide another intriguing difference between the previous studies. 22,23,[25][26][27] They show that increased HSF-1 expression results in increased PAI-1 expression in endothelial cells stimulated with glycated low-density lipoprotein or oxidized very-low-density lipoprotein. Although in both scenarios, HSF-1 increases, the regulation of PAI-1 seems to be stimulus-specific (statin versus lipoproteins).…”

“…Uchiyama et al 22 showed that simvastatin increased TM and eNOS expression and translocation of HSF-1 and decreased PAI-1 expression. These pleiotropic effects were mimicked by a constitutive active form of human HSF-1.…”

“…21 Experimental data indicate that statins induce heat shock factor (HSF)-1 translocation (via eNOS) to the nucleus, activating promoter genes of TM and tPA and downregulating PAI-1 expression. 19,22 Until now, a thorough exploration was missing of responsible signaling pathways for these antithrombotic effects of statins.…”