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Relation of plaque lipid composition and morphology to the stability of human aortic plaques
C V Felton1, D Crook, M J Davies
1Wynn Department of Metabolic Medicine, Imperial College School of Medicine, National Heart and Lung Institute, London, United Kingdom.
Insights
Atherosclerotic plaque rupture is linked to lipid content and distribution. Disrupted plaques show higher lipid content, more macrophages, and thinner caps, suggesting lipid profiles influence plaque vulnerability.
Area of Science:
- Cardiovascular Biology
- Atherosclerosis Research
- Lipid Metabolism
Background:
- Atherosclerotic plaques can rupture, leading to cardiovascular events.
- The lipid composition and distribution within plaques are suspected to influence rupture propensity.
Purpose of the Study:
- To investigate the relationship between plaque lipid profiles, morphology, and disruption.
- To compare lipid content and distribution in intact versus disrupted human aortic plaques.
Main Methods:
- Analysis of morphological and lipid profiles of 668 human aortic plaques from deceased individuals.
- Classification of plaques into disrupted, intact type A, and intact type B categories.
- Quantification of lipids, cholesterol, fatty acids, and macrophage content.
Main Results:
- Disrupted plaques had significantly higher lipid and macrophage content and thinner caps compared to intact plaques.
- Lipid concentrations correlated positively with macrophage accumulation and negatively with cap thickness.
- Differences in free-to-esterified cholesterol ratios and fatty acid profiles were observed between plaque types and locations (center vs. edge).
Conclusions:
- Lipid composition and intraplaque lipid distribution differ significantly between intact and disrupted atherosclerotic plaques.
- Increased esterified lipids at the plaque edge, associated with thinner caps, may indicate macrophage activity and predisposition to rupture.
Abstract:
The propensity of atherosclerotic plaques to disrupt may be influenced by their lipid content and the distribution of these lipids within the plaque. To investigate this, we analyzed the morphological and lipid profiles of 668 human aortic plaques from 30 males who had died of ischemic heart disease. Plaques were classified as disrupted or as intact types A or B, the latter distinction being based on the absence or presence, respectively, of disrupted plaques within the same aorta. Disrupted plaques have a greater content of lipid (P < .001) and macrophages (P < .001) as well as a thinner cap (P < .001) than intact plaques. Lipid concentrations are positively associated with macrophage accumulation in all plaque types and are negatively associated with minimum cap thickness at the edge of disrupted plaques (P < .05). Free cholesterol concentration is inversely associated with minimum cap thickness at the center of type B plaques only (P < .05). At the center of intact type A and B and disrupted plaques, the free-to-esterified cholesterol ratios were 0.9 (range, 0.0 to 2.7), 0.8 (0.0 to 3.9), and 1.6 (0.2 to 4.0), respectively. Esterified cholesterol concentrations were higher at the center of type B plaques, and those of free cholesterol were higher at the center of disrupted plaques. At the edge of disrupted plaques, the free-to-esterified cholesterol ratio was 0.5 (0.0 to 2.7) because of the accumulation of esterified cholesterol. Concentrations of all fatty acids were increased at the edge of disrupted plaques compared with the center, but as a proportion of total fatty acids, omega 6-polyunsaturated fatty acids (PUFAs) were lower (44% versus 46%, P < .01), possibly reflecting oxidation of PUFAs. These data demonstrate differences in lipid composition and intraplaque lipid distribution between intact and disrupted plaques. At the edge of advanced plaques, increased esterified lipid concentrations, inversely associated with cap thickness, may reflect macrophage activity and a predisposition to rupture.