Dog models of human atherosclerotic cardiovascular diseases.

Abstract

Cardiovascular diseases (CVD) are one of the leading causes of death worldwide. Eighty-five percent of CVD-associated deaths are due to heart attacks and stroke. Atherosclerosis leads to heart attack and stroke through a slow progression of lesion formation and luminal narrowing of arteries. Dogs are similar to humans in terms of their cardiovascular physiology, size, and anatomy. Dog models have been developed to recapitulate the complex phenotype of human patients and understand the underlying mechanism of CVD. Different methods, including high-fat, high-cholesterol diet and genetic modification, have been used to generate dog models of human CVD. Remarkably, the location and severity of atherosclerotic lesions in the coronary arteries and branches of the carotid arteries of dog models closely resemble those of human CVD patients. Overt clinical manifestations such as stroke caused by plaque rupture and thrombosis were observed in dog models. Thus, dog models can help define the pathophysiological mechanisms of atherosclerosis and develop potential strategy for preventing and treating CVD. In this review, we summarize the progress in generating and characterizing canine models to investigate CVD and discuss the advantages and limitations of canine CVD models.