Mechanisms Underlying Pleiotropic Effects of Statins

Abstract

Statins are the most efficacious hypolipidemic drugs available. Numerous meta-analyses of clinical trials have provided unequivocal evidence that statins are effective and safe in preventing cardiovascular morbidity and mortality in patients with and without pre-existing ischemic heart disease. With widespread usage of statins, its actions other than that of lipid-lowering have started to emerge. Although the effects of statins were initially attributed to a reduction in lipid levels, many benefits are now considered to stem from effects other than lipid modulation. In this review, we describe the mechanisms of these pleiotropic effects and the pathways involved in these effects.

Wpływ leczenia hipolipemicznego na wydzielanie cytokin prozapalnych w różnych grupach wiekowych pacjentów z cukrzycą typu 2 i dyslipidemią aterogenną

“…inflammatory, antioxidant, and antithrombotic properties, and improve endothelial function [21][22][23][24] and both lipid-and non-lipid-related mechanisms participating in the reduction of cardiovascular endpoints in statin [8,9] and some fibrate trials [19,20]. Interestingly, in one of our previous studies, simvastatin and fenofibrate reduced monocyte cytokine release but this effect was not stronger if both drugs were administered together [18].…”

Low-dose atorvastatin reduces ambulatory blood pressure in patients with mild hypertension and hypercholesterolaemia: a double-blind, randomized, placebo-controlled study

“…The beneficial actions of statins on vasculature include reduction of vascular inflammation, improvement of insulin sensitivity and endothelial function, inhibition of vascular smooth muscle cells migration and proliferation, reduction of oxidant stress, and inhibition of platelet adhesion. 4,5 In this context, it has been suggested that statin treatment may be also associated with a mild hypotensive effect. Blood pressure (BP) reductions with statin treatment were originally revealed in different animal models of hypertension.…”

Effect of Statin Therapy on the Progression of Autosomal Dominant Polycystic Kidney Disease. A Secondary Analysis of the HALT PKD Trials

“…Other effects of statins include improvement of endothelial dysfunction by upregulating endothelial and vascular smooth muscle cell production of nitric oxide 25,30,31 . Endothelial dysfunction is an early feature of ADPKD 32–37 and may account for the decreased renal blood flow observed in young people with ADPKD 38,39 .…”

“…Because statins have anti-inflammatory and anti-oxidant effects 25,31,43 , they have been studied for the prevention of acute kidney injury after cardiac surgery, a state of an intense systemic inflammatory response, with mixed results 26,44 . Renal interstitial inflammation and oxidative stress are prominent features of ADPKD, resulting in dense fibrosis, tubular atrophy and glomerulosclerosis 45–48 .…”