Animal models of atherosclerosis and interpretation of drug intervention studies.
Atherosclerosis has often been defined as a multifactoral disease; however, a common risk factor associated with accelerated vascular disease in man or animals is an elevated plasma cholesterol level. Even though there is no one perfect animal model that completely replicates the stages of human atherosclerosis, cholesterol feeding and mechanical endothelial injury are two common features shared by most models of atherosclerosis. The models may differ with respect to degree of dietary cholesterol supplementation, length of hypercholesterolemia, dietary regimen and type, duration and degree of mechanical endothelial injury. With the advent of genetic engineering, transgenic mouse models have supplemented the classical dietary cholesterol induced disease models such as the cholesterol-fed hamster, rabbit, pig and monkey. The desire to limit the progression of atherosclerosis has spawned numerous drug intervention studies. Biochemical as well as morphologic and morphometric changes in the extent, structure and composition of atherosclerotic lesions following drug intervention have become major endpoints of in vivo drug intervention studies. Interpretations of alterations in vascular pathology following drug administration are often confounded by associated changes in plasma lipids and lipoproteins, limitation of the animal models and additional properties of compounds unrelated to their primary mode of action. Thus, the current review will summarize the pathology of atherosclerosis, describe various animal models of vascular disease and provide a critical review of the methods utilized and conclusions drawn when evaluating pharmacologic agents in animals.
Bocan
T M
TM
Department of Vascular and Cardiac Diseases, Parke-Davis Pharmaceutical Research, Division of Warner Lambert Company, Ann Arbor, MI 48105, USA.
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001161:Arteriosclerosis / Q000188:drug therapy* / Q000473:pathology; D006224:Cricetinae; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D016859:Lipoxygenase Inhibitors; D051379:Mice; D008822:Mice, Transgenic; D011817:Rabbits; D013045:Species Specificity; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors; D013552:Swine
D000975:Antioxidants; D004791:Enzyme Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D016859:Lipoxygenase Inhibitors; D002785:Sterol O-Acyltransferase