Journal Article

Anti-Inflammatory Effects of Statins: Clinical Evidence and Basic Mechanisms

Jain, Mukesh K., Ridker, Paul M.

2005

Overview

Key Points Recent evidence has shown that the statins, a class of drugs originally designed to manage cardiovascular disorders by lowering cholesterol might, in part, mediate their protective effects by reducing inflammation. Statin-mediated inhibition of inflammation might affect outcomes in cardiovascular trials independently of the extent of lipid-lowering achieved. The role of inflammation in atherogenesis, combined with the observation that statins show benefit in conditions that are not strongly associated with hyperlipidaemia, led to studies into the additional effects of statins. In the clinic, evidence that statins could have favorable and clinically relevant anti-inflammatory effects independent of lipid lowering is derived from studies of endothelial function, clinical trials of organ transplantation, and clinical trials of myocardial infarction and stroke prevention. Of potential interest is the statin-induced reduction of C-reactive protein (CRP), a marker for inflammation; recent data suggests that the CRP-lowering effect of statins might, in addition to lipid lowering, be relevant for progression of disease. Data from experiments in cell culture and animal models show that statins can induce the cellular accumulation of endothelial nitric oxide synthase; inhibit the expression of adhesion molecules and chemokines that recruit inflammatory cells; inhibit expression of pro-coagulant factors and induce anti-coagulant substances; inhibit proliferation and promote apoptosis of vascular smooth muscle cells; and ameliorate platelet hyper-reactivity. Pathways/factors implicated in the cellular effects of statins include the cholesterol biosynthesis pathway, Ras/Rho, nuclear factor-κB and activator protein-1-mediated pro-inflammatory pathways, and nuclear factors such as peroxisome proliferator-activated receptor and Kruppel-like factor-2. Future studies of the benefits of statins will need to focus on anti-inflammatory targets and will need to take into account interindividual variation to the drugs. Chronic inflammation is a key feature of vascular disease states such as atherosclerosis. Multiple clinical studies have shown that a class of medications termed statins lower cardiovascular morbidity and mortality. Originally developed to lower serum cholesterol, increasing evidence suggests that these medications have potent anti-inflammatory effects that contribute to their beneficial effects in patients. Here, we discuss the clinical and experimental evidence underlying the anti-inflammatory effects of these agents.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: Anti-Inflammatory Agents - pharmacology / Anti-Inflammatory Agents - therapeutic use / Atherosclerosis - drug therapy / Biomedical and Life Sciences / Biomedicine / Biotechnology / Cancer Research / Cardiovascular diseases / Drug therapy / Health aspects / Humans / Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology / Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use / Inflammation / Inflammation - drug therapy / Medicinal Chemistry / Molecular Medicine / Pharmacology/Toxicology / review-article / Statins