Cholesterol crystallization and macrophage apoptosis: implication for atherosclerotic plaque instability and rupture.
The presence of abundant cholesterol crystals symbolizes the disorder of cholesterol metabolism during the development of atherosclerosis. Examination of cultured human THP-1 macrophages treated with the cholesterol oxide, 7-ketocholesterol, revealed a concentration- and time-dependent increase in formation of cholesterol crystals in the cells. Radioisotope labeling and X-ray diffraction confirmed the presence of 7-ketocholesterol crystalline domains (d space 35.8A). Under the normal cell culture condition (5% CO(2), 37 degrees ), incubation with 7-ketocholesterol induced moderate levels of apoptosis. Elevating temperature from 37 to 40 degrees markedly reduces formation of the crystals in the macrophages. Meanwhile, at high temperatures, significantly increased numbers of apoptotic cells were detected in the cells treated with 7-ketocholesterol but not in those with native free cholesterol. These results suggest that hyperthermia inhibits cholesterol crystallization and promotes apoptotic effects of oxysterols on macrophages.
Geng
Yong-Jian
YJ
Center for Cardiovascular Biology and Atherosclerosis, University of Texas Health Science Center at Houston School of Medicine, 6431 Fannin Street, MSB 6.001, Houston, TX 77030, USA. yong-jian.geng@uth.tmc.edu
Phillips
Jane Ellen
JE
Mason
R Preston
RP
Casscells
S Ward
SW
D017209:Apoptosis; D001161:Arteriosclerosis / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D002462:Cell Membrane; D002784:Cholesterol / Q000737:chemistry*; D003460:Crystallization; D006801:Humans; D008264:Macrophages / Q000473:pathology*; D012421:Rupture / Q000209:etiology*; D013696:Temperature; D013816:Thermodynamics
D002784:Cholesterol