Preclinical Evaluation Methods for Screening of Anti-Atherosclerotic Drugs: An Overview

Abstract

Atherosclerosis is a disease of large and medium-sized muscular arteries and is characterized by endothelial dysfunction, vascular inflammation, and the buildup of lipids, cholesterol, calcium, and cellular debris within the intima of the vessel wall. This buildup results in plaque formation, vascular remodeling, acute and chronic luminal obstruction, abnormalities of blood flow and diminished oxygen supply to target organs. Vasomotor function, the thrombogenicity of the blood vessel wall, the state of activation of the coagulation cascade, the fibrinolytic system, smooth muscle cell migration and proliferation, and cellular inflammation are complex and interrelated biological processes that contribute to atherogenesis and the clinical manifestations of atherosclerosis. Elevated serum levels of low-density lipoprotein cholesterol overwhelm the antioxidant properties of the healthy endothelium and result in abnormal endothelial metabolism of this lipid moiety. Oxidized low-density lipoprotein is capable of a wide range of toxic effects and cell/vessel wall dysfunctions that are characteristically and consistently associated with the development of atherosclerosis. Detail study of atherosclerosis can be done by using various animal models. Animals different species mainly use for screening methods are mice, rats, rabbits, squil, hamsters, guinea pig. Various animal models are hyperlipidemic model, hypercholestermic model, hypolipidemic model, hereditary hypercholestermic model hereditary hyper lipidemic model, transgenic model. These models are used to observed effect of drug on diseased animal and find out various drugs for treatment of atherosclerosis disease.