Hypercholesterolemia Causes Mechanical Weakening of Rabbit AtheromaLocal Collagen Loss as a Prerequisite of Plaque Rupture
作者:
Mark Rekhter,
Gary Hicks,
David Brammer,
Hussein Hallak,
Erick Kindt,
Jing Chen,
Wendy Rosebury,
Maureen Anderson,
Paul Kuipers,
Michael Ryan,
期刊:
Circulation Research: Journal of the American Heart Association
(OVID Available online 2000)
卷期:
Volume 86,
issue 1
页码: 101-101
ISSN:0009-7330
年代: 2000
出版商: OVID
关键词: arteriosclerosis;cholesterol;collagen;macrophage;plaque rupture
数据来源: OVID
摘要:
Hypercholesterolemia may render atherosclerotic plaques prone to rupture. To test this hypothesis, catheters with matrix-covered balloons were implanted into the aorta of rabbits fed standard or 0.5% cholesterol chow (n=70). In 1 month, fibrous plaques developed around the balloon. Time-dependent accumulation of cholesteryl esters and free cholesterol was detected in the plaques of the cholesterol-fed group only. The pressure needed to rupture the plaque by balloon inflation was used as an index of plaque strength. Three months after the catheter implantation, the breaking pressure was 2.1 times lower (P<0.05) in cholesterol-fed rabbits. It was accompanied by collagen loss, as measured by plaque hydroxyproline content, but not with deficiency of collagen cross-linking. Sirius red staining showed preservation of collagen originally covering the balloon and accumulation of nascent collagen in the lesions of standard chow-fed rabbits. In the cholesterol-fed group, both mature and new collagen underwent degradation predominantly in the plaque shoulders. Collagen breakdown was associated with local accumulation of foamy macrophages. Gel zymography demonstrated relative enhancement of gelatinolytic activity at 92 and 72 kDa, as well as caseinolytic activity at 57, 45, and 19 kDa in the lipid-laden plaques. Lipid accumulation in the plaque was also associated with a loss of smooth muscle cells, the cellular source of the collagen fibers. The remaining smooth muscle cells showed increased collagen synthesis, although it was insufficient to counterbalance collagen degradation and cell loss. Thus, we have obtained direct evidence that hypercholesterolemia is accompanied by enhanced local collagen degradation, which is potentially responsible for plaque weakening.
返 回