Antioxidant Effects of Statins in the Management of Cardiometabolic Disorders

Abstract

Redox systems are key players in vascular health. A shift in redox homeostasis-that results in an imbalance between reactive oxygen species (ROS) generation and endogenous antioxidant defenses has the potential to create a state of oxidative stress that subsequently plays a role in the pathogenesis of a number of diseases, including those of the cardiovascular and metabolic system. Statins, which are primarily used to reduce the concentration of low-density lipoprotein cholesterol, have also been shown to reduce oxidative stress by modulating redox systems.Studies conducted both in vitro and in vivo support the role of oxidative stress in the development of atherosclerosis and cardiovascular diseases. Oxidative stress may also be responsible for various diabetic complications and the development of fatty liver. Statins reduce oxidative stress by blocking the generation of ROS and reducing the NAD＋/NADH ratio. These drugs also have effects on nitric oxide synthase, lipid peroxidation and the adiponectin levels.It is possible that the antioxidant properties of statins contribute to their protective cardiovascular effects, independent of the lipid-lowering actions of these agents. However, possible adverse effects of statins on glucose homeostasis may be related to the redox system. Therefore, studies investigating the modulation of redox signaling by statins are warranted. J Atheroscler Thromb, 2014; 21:997-1010.

Acute simvastatin treatment restores cerebral functional capillary density and attenuates angiotensin II‐induced microcirculatory changes in a model of primary hypertension

“…Statins that are primarily used to reduce cholesterol levels also have the potential to reduce oxidative stress through redox system modulation . Protective cardiovascular effects of statins may be directly associated with their antioxidant properties, independent of the cholesterol‐lowering of these agents .…”

Statin action enriches HDL3 in polyunsaturated phospholipids and plasmalogens and reduces LDL-derived phospholipid hydroperoxides in atherogenic mixed dyslipidemia

“…A simple explanation may derive from statin-mediated reduction in systemic oxidative stress, prevalent in MetS (3,23,52). However, as the major source of circulating plasmalogens in humans is the liver, and as their synthesis is independent of that of cholesterol, several additional mechanisms may contribute.…”

“…One involves reduction in oxidative PUPC degradation as a result of statin-induced decrement in the production of ROS (52). A second may arise from enhanced protection of HDL3-PUPC against oxidative degradation due to elevated poststatin content of plasmalogens in HDL3 (see below); these lipids are highly effective antioxidants (33)(34)(35)(36)(37).…”

Antioxidant properties of drugs used in Type 2 diabetes management: could they contribute to, confound or conceal effects of antioxidant therapy?

“…The antioxidant effects of statins have come under intense research [90][91][92]. Atorvastatin has decreased superoxide production in human endothelial cells exposed to high glucose, and also protected these cells from hydrogen peroxide mediated damage [93,94].…”