Pleiotropic Effects of Statins in Atherosclerotic Disease: Focus on the Antioxidant Activity of Atorvastatin

Abstract

Cardiovascular diseases, which are the leading cause of mortality in the Western World, are closely associated with atherosclerosis development. Atherosclerosis is a chronic multifactorial disease of the arterial wall characterized by endothelial dysfunction, inflammation and oxidative stress. Oxidative stress is an alteration of the balance between pro-oxidant and antioxidant mechanisms which promotes vascular complications and represents a valid therapeutic target to prevent or treat cardiovascular diseases. Statins are enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors that have been included in the therapeutic regimen of cardiovascular diseases due to their lipid-lowering activity. Experimental and clinical data demonstrated that the antiatherogenic effects of these drugs are also related to other pleiotropic activities, particularly to their anti-inflammatory, anti-thrombotic and antioxidant effects. This review summarizes experimental and clinical studies demonstrating the impact of statins on atherosclerotic disease with a focus on the antioxidant activity of atorvastatin. Atorvastatin is a synthetic statin characterized by a high efficacy, in part due to its longer half-life compared to other molecules of the same group. It also exerts high antioxidant effects, independent from its hypolipidemic activity, beneficial for the prevention and therapy of atherosclerosis.

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].…”

The Characteristics and Roles of Advanced Oxidation Protein Products in Atherosclerosis

“…These drugs prevent the increase in the thickness of the intimal-medial layer of the carotid arteries, which is a surrogate marker of atherosclerosis [102]. Their antiatherosclerotic effects are caused not only by their lipid-lowering activity but also by their anti-inflammatory, antioxidant, anti-platelet and immunomodulation properties [103,104]. Lipid-lowering drugs from other groups are also effective as antiatherosclerotic agents.…”

Hypercholesterolemia and Hypertension: Two Sides of the Same Coin

“…Statins are known to have pleiotropic effects that go beyond lowering the cholesterol level [60][61][62][63]. They improve endothelial-dependent vasodilation, increase the bioavailability of NO, decrease levels of oxidized LDL cholesterol, reduce levels of endothelin-1, affect the immunological system, stabilize atherosclerotic plaque, decrease synthesis of aldosterone, inhibit the proliferation of vascular smooth muscle cells and platelet aggregation, and reduce vascular inflammation.…”