Statins Effect on Smooth Muscle Cell Proliferation

Abstract

Clinical trials have firmly established that 3-hydroxy-3-methylglutaryl-coenzyme-A reductase inhibitors (statins) can induce regression of vascular atherosclerosis as well as reduction of cardiovascular-related morbidity and death in patients with and without coronary artery disease. These beneficial effects of statins are usually assumed to result from their ability to reduce cholesterol synthesis. However, because mevalonic acid is the precursor not only of cholesterol but also of many nonsteroidal isoprenoid compounds, inhibition of 3-hydroxy-3-methylglutaryl-coenzyme-A reductase may result in pleiotropic effects. Indeed, statins can interfere with major events involved in the formation and the evolution of atherosclerotic lesions, such as arterial myocyte migration and proliferation and cholesterol accumulation, independent of their hypolipidemic properties. The aim of this article is to focus on clinical and experimental data that show that statins possess effects beyond cholesterol lowering, particularly on arterial smooth muscle cell proliferation. The contribution of these direct vascular effects to the reduction of cardiovascular events observed in clinical trials with statins represents one of the major challenges for future studies to understand the antiatherosclerotic benefits of these agents.

Amelioration of Human Allograft Arterial Injury by Atorvastatin or Simvastatin Correlates With Reduction of Interferon-γ Production by Infiltrating T Cells

“…Specifically relevant to GA, statins were reported to selectively inhibit several pro-inflammatory mediators including interleukin (IL)-2, IL-12, interferon (IFN)-γ, tumor necrosis factor-α, as well as a number of chemokines, adhesion molecules, co-stimulatory molecules and transcription factors (9). Additionally, an association between statins and reduction of endothelial dysfunction (10) and VSMC proliferation (11), both potentially important to the pathobiology of GA, has also been suggested. Also, the incidence of coronary allograft vasculopathy after heart transplantation was reduced (12), and improved functional outcomes after kidney transplantation were reported in association with statin administration (13).…”

A Quantitative Systems Pharmacology Platform to Investigate the Impact of Alirocumab and Cholesterol-Lowering Therapies on Lipid Profiles and Plaque Characteristics

“…Known PK parameters for statin therapy were taken from package inserts and the literature. 19,20 We included known mechanisms of action for statins, ezetimibe, and fibrates into the model and calibrated the parameters influencing the pharmacodynamic effect of each drug to the average clinical response across clinical trial data reported in the literature. 5,20–24 …”

Role of MutS homolog 2 (MSH2) in intestinal myofibroblast proliferation during Crohn's disease stricture formation

“…Simvastatin was chosen because of the known antioxidant effect of this drug group (10), and the effect of statins on muscle cell metabolism (within the vascular system) has been well characterized (2). It has been shown that simvastatin increases the expression of two DNA repair proteins, MLH1 and XRCC1; thus MSH2 suppression by simvastatin is likely to be a very specific and not a general phenomena in the repair system (37).…”