The role of oxidative stress and autophagy in atherosclerosis.

Ida Perrotta,Saveria Aquila

doi:10.1155/2015/130315

Abstract

Atherosclerosis is a multifactorial, multistep disorder of large- and medium-sized arteries involving, in addition to age, gender and menopausal status, a complex interplay between lifestyle and genetic risk factors. Atherosclerosis usually begins with the diffusion and retention of atherogenic lipoproteins into the subendothelial space of the artery wall where they become oxidized by local enzymes and accumulate, leading to the formation of a cushion called atheroma or atheromatous or fibrofatty plaque, composed of a mixture of macrophages, lymphocytes, smooth muscle cells (SMCs), cholesterol cleft, necrotic debris, and lipid-laden foam cells. The pathogenesis of atherosclerosis still remains incompletely understood but emerging evidence suggests that it may involve multiple cellular events, including endothelial cell (EC) dysfunction, inflammation, proliferation of vascular SMCs, matrix (ECM) alteration, and neovascularization. Actually, a growing body of evidence indicates that autophagy along with the chronic and acute overproduction of reactive oxygen species (ROS) is integral to the development and progression of the disease and may represent fruitful avenues for biological investigation and for the identification of new therapeutic targets. In this review, we give an overview of ROS and autophagy in atherosclerosis as background to understand their potential role in this vascular disease.

Highlights

Reactive oxygen (ROS) and nitrogen species (RNS) are highly reactive molecules, either endogenously produced during normal metabolism in the body or exogenously introduced by the environment
Oxidation of low-density lipoprotein (LDL) is one of the earliest events in atherogenesis and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase has been demonstrated to be critically involved in this process in both mice and humans by acting either directly or indirectly as a precursor of reactive oxygen species (ROS) which are utilized as substrates by other enzymes to generate more powerful oxidizing species [5,6,7]
Several lines of evidence indicate that ROS are the upstream modulators of autophagy and that oxidative stress coupled with defective autophagy may play a fundamental role in regulating atherosclerotic plaque development

Summary

Introduction

Reactive oxygen (ROS) and nitrogen species (RNS) are highly reactive molecules, either endogenously produced during normal metabolism in the body or exogenously introduced by the environment. Among these classes of molecules, those deriving from ROS have great biological impact because they are endogenously produced and can damage virtually all classes of macromolecules at high concentrations [1]. Oxidation of LDL is one of the earliest events in atherogenesis and NADPH oxidase has been demonstrated to be critically involved in this process in both mice and humans by acting either directly or indirectly as a precursor of ROS which are utilized as substrates by other enzymes to generate more powerful oxidizing species [5,6,7]. This type of autophagy, called lipophagy, was first demonstrated in the liver and has become a subject of intense research interest with potentially profound implications for the treatment of the diseases associated with dyslipidemias, such as diabetes and atherosclerosis [17, 18]

NADPH Oxidase as the Major Culprit of Oxidative Stress in Atherosclerosis

Self-Eating in Atherosclerosis

Concluding Remarks