Pathogenesis of atherosclerosis: A multifactorial process

Abstract

Atherosclerosis is a leading cause of mortality and morbidity in the western world. It has been recognized for over a century, and the understanding of its pathogenesis has undergone many changes. Pathophysiological studies have unravelled the interactions of molecular and cellular elements involved in atherogenesis. The focus has shifted to the novel risk factors as well as characteristics and stability of atherosclerotic plaque; the genetic predisposition has further broadened the pathogenetic mechanisms. This review focuses on the molecular mechanisms involved in the evolution of the atherosclerotic plaque that may pave the way for selecting optimal therapies and preventing plaque complications. Atherosclerosis is no longer a disease attributed mainly to the high lipid content of the body. New insight into the disease pathology has shown it to be a disease of much greater ramifications. Endothelial damage and reactive oxygen species (and other free radicals) have predominantly emerged as factors in virtually all pathways leading to the development of atherosclerosis due to hyperlipidemia, diabetes, hypertension or smoking. Novel risk factors such as hyperhomocysteinemia, infections and systemic lupus erythematosus have emerged. Atherosclerosis has come to be regarded as a chronic inflammatory disease with an autoimmune component. The genetic basis of the disease assumes significance as candidate genes are identified and gene therapy becomes a promising new addition to the existing, less substantial conventional therapies.

Keywords: Angiotensin; Atherogenesis; Cytokines; Growth factors; Oxidized low density lipoproteins; Plaque formation; Reactive oxygen species.

Figure 1)

Schematic design depicting the involvement of oxidized low density lipoprotein (oxLDL), injury of endothelial cells and proliferation of vascular smooth muscle cells (SMC) in the development of atherosclerotic plaque. MAP Mitogen-activated protein

Figure 2)

Schematic diagram depicting the involvement of reactive oxygen species, endothelial dysfunction, growth factors, cytokines and adhesion molecules in the genesis of atherosclerosis. LDL Low density lipoprotein