Direct in vivo evidence of a vascular statin: a single dose of cerivastatin rapidly increases vascular endothelial responsiveness in healthy normocholesterolaemic subjects

Abstract

Aims HMG-CoA reductase inhibitors (statins) have been demonstrated to have in vitro vascular effects. The aim of this study was to determine whether statins actually have in vivo vascular effects independent of their cholesterol-lowering effect. Methods We investigated the effect of a single dose of cerivastatin on vascular endothelial function by measuring flow-mediated dilatation of the brachial artery on ultrasound in 30 healthy volunteers with normal serum cholesterol concentrations. They were randomized to either placebo group ( n = 15) or cerivastatin group ( n = 15), and flow-mediated dilatation and endothelium-dependent dilatation were evaluated at before and 1 h, 3 h, 6 h, and 12 h after administration of placebo or cerivastatin. Results There were no differences in total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, malondialdehyde-LDL, and high-sensitivity C-reactive protein before and after administration of placebo or cerivastatin. Cerivastatin significantly increased flow-mediated dilatation at 3 h ( P < 0.001), and this increase rapidly returned to the baseline level 6 h after administration. Endotheliumindependent dilatation of brachial artery was not altered. Conclusions A single dose of cerivastatin increased vascular endothelial responsiveness. Our data suggest that cerivastatin has a direct effect on the blood vessels that is independent of its lipid-lowering effect, and thus can be considered as a vascular statin.

The Status of Lipid Management in 1,836 Patients with Coronary Artery Disease: A multicenter survey to evaluate the percentage of Japanese coronary artery disease patients achieving the target low-density lipoprotein cholesterol level specified by the Japan Atherosclerosis Society

“…Pleiotropic beneficial effects of statins on vascular wall independent of their lipid-lowering action have also been demonstrated by recent basic and clinical investigations (13)(14)(15)(16)(17)(18). In the present study, however, only 36.3% of patients received statin therapy.…”

Acute Protective Effects of Simvastatin in the Rat Model of Renal Ischemia-Reperfusion Injury: It Is Never Too Late for the Pretreatment

“…Consequently, the effects of simvastatin on tubular necrosis were rapid and short, occurring probably at the beginning of reperfusion. Acute (3 h), transient effect of a single dose of cerivastatin on endothelial responsiveness in humans has already been reported by Omori et al (10). Rapid effects of simvastatin could be explained, at least in part, by regulation of NO production and activity (stabilization of eNOS mRNA, stabilization of eNOS protein, or a direct influence on eNOS activity) (10).…”

Single-Dose Intravenous Simvastatin Treatment Attenuates Renal Injury in an Experimental Model of Ischemia-Reperfusion in the Rat

“…The observed effects of simvastatin probably could not be explained by the cholesterol lowering effects of statins (taking at least two weeks of therapy) [a single dose of simvastatin (1 mg / kg) was not expected to significantly influence the lipid profile of rats (I / R + simvastatin or Sham-operated + simvastatin); because of this, the lipid profile was not measured] or the increased expression of eNOS (occurring after 3 days of statin pretreatment). On the other hand, certain effects of statins occurring after a few hours of pretreatment may fit into our experimental model, for example, their effects on the regulation of NO production and activity (stabilization of NOS mRNA, stabilization of NOS protein, or a direct influence on NOS activity) (8,14). Some acute protective effects of statins in similar experimental models of I / R injury of the kidney and heart have been already shown (3,13).…”