Guinea pigs as models to study the hypocholesterolemic effects of drugs

Guinea pigs are useful models to investigate the mechanisms of the hypocholesterolemic effects of drugs. Like humans, guinea pigs are one of the few species that carry the majority of cholesterol in LDL. This animal model has also been shown to develop atherosclerosis when challenged with hypercholesterolemic diets. In addition, plasma lipid profiles in males, females and ovariectomized guinea pigs, a model for menopause, follow similar patterns to those observed in humans. In this report, drugs aimed at lowering plasma cholesterol and triglycerides in hyperlipidemic individuals are reviewed. Studies analyzing the hypolipidemic effect of HMG-CoA reductase inhibitors, acyl CoA cholesterol acyltransferase inhibitors, fibrates, bile acid resins, apical sodium bile acid transporter inhibitors, and others show that guinea pigs and humans have comparable responses to drug therapy. In addition, results from the limited clinical reports addressing specific effects of drugs on LDL catabolism or VLDL synthesis are in agreement with observations in guinea pigs. From the review of these studies, it is apparent that the guinea pig is a useful animal model to further explore the mechanisms of action of lipid lowering drugs including effects on specific receptors and regulatory enzymes involved in cholesterol metabolism and on early atherosclerosis development.

ACAT, acyl-CoA:cholesterol acyltransferase; ASBT, apical sodium co-dependent bile acid transporter; ApoB, apolipoprotein B; CHD, coronary heart disease; CYP7, cholesterol 7alpha-hydroxylase; HDL, high density lipoprotein; HMG-CoA, 3-hydroxy-3-methylglutaryl coenzyme A; FCR, free catabolic rate; LDL, low density lipoprotein; PPAR, peroxisome proliferators-activated receptor; TC, total cholesterol; TG, triglycerides; VLDL, very low density lipoprotein.