Cellular events in the development of valvular atherosclerotic lesions induced by experimental hypercholesterolemia.
The onset and evolution of ultrastructural changes in the cardiac valves induced by a cholesterol-rich diet were investigated in rabbit and hamster. In both animal models, the atrioventricular and sigmoid valves were comparably affected by lesions intermediary between fatty streak and fibrous plaque. The earliest detectable modification was the progressive accumulation in the subendothelium of extracellular liposome-like structures rich in unesterified cholesterol, associated with the proliferation of a basal lamina-like material. This was followed by the diapedesis of blood monocytes in the same location, which became macrophages increasingly loaded with lipid deposits. Resident interstitial cells accumulate lipids, as well. In advanced stages, the macrophage-derived foam cells clustered, deforming the valve leaflets. The resident macrophages accumulated lipids later and more slowly, while partly preserving their ultrastructure. The advanced lesions are characterized by marked stromal proliferation, massive intra- and extracellular deposition of lipids and cholesterol crystals and the appearance of a necrotic core. The salient findings of these studies were: (1) the appearance of extracellular liposomes as the earliest event in atherogenesis; (2) the capability of the valvular interstitial cells to accumulate lipids; and (3) the slow response of resident macrophages to the cholesterol-rich diet. The results revealed that hypercholesterolemia produces in the cardiac valves atherosclerotic lesions of an intermediate type, which can deform the leaflets thus altering their normal function.
Filip
D A
DA
Institute of Cellular Biology and Pathology, Bucharest, Romania.
Nistor
A
A
Bulla
A
A
Radu
A
A
Lupu
F
F
Simionescu
M
M
D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology / Q000473:pathology*; D006224:Cricetinae; D004036:Diet, Atherogenic; D006351:Heart Valves / Q000473:pathology* / Q000648:ultrastructure; D006937:Hypercholesterolemia / Q000150:complications / Q000473:pathology*; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood; D008081:Liposomes; D008264:Macrophages / Q000648:ultrastructure; D008297:Male; D008647:Mesocricetus; D009000:Monocytes / Q000648:ultrastructure; D011817:Rabbits
D008055:Lipids; D008081:Liposomes