Experimental obstructive coronary atherosclerosis in the hyperlipidemic hamster.

The evolution of coronary atherosclerotic lesions induced by a hyperlipidemic diet was examined in male hamsters subjected for up to 40 weeks to a standard chow supplemented with 3% cholesterol and 15% butter. Control animals were fed standard chow only. Five to seven hamsters were monthly sacrificed and investigated for serum lipids and coronary artery lesions. As compared with control animals, the hamsters fed the fat diet showed a progressive increase in serum cholesterol which reached maximum values up to 17 fold in the 10th month. The serum of the hyperlipidemic hamster examined by agarose electrophoresis, Laurell immunoelectrophoresis and cross-immunoelectrophoresis showed at most a 14 fold increase in low density lipoproteins after 10 months diet. The examination of coronary arteries revealed morphologic changes already detectable at 2 weeks of diet. The earliest modifications observed were characterized by proliferation of the subendothelial matrix or/and the appearance of liposome-like structures in the intima. After 2-3 weeks of diet, smooth muscle cells appeared occasionally in the intima and monocytes adhered and penetrated through the endothelium. Later on, smooth muscle cells and macrophage displayed lipid deposits. Focally, in areas of intimal proliferation and foam cells, endothelial cells were also lipid-loaded. Like in human atherosclerotic plaque, in the late stages of hamster coronary lesions, there was a progressive accumulation of extracellular unesterified cholesterol, calcium deposition and necrosis. Lesions evolved to a progressive narrowing of the coronary branches affected, with complete obstruction of some small arterial ramifications. Hamster appears to be a suitable model for studying the molecular and cellular events leading to obstructive coronary atherosclerosis.