Oxysterols in cap and core of human advanced atherosclerotic lesions

Objective: Different parts of the advanced atherosclerotic lesion have characteristic differences in lipid content, but the distribution of lipid oxidation products has not been reported. This study provides novel data on oxysterol and hydroxyoctadecadienoic acids quantification in core versus cap. It compares the lipid composition of core and cap to assess the topographical distribution of evidence of lipid oxidation. Methods: Lipids and oxidised lipids were analysed by gas chromatography (GC) and GC-mass spectrometry (GC-MS) in samples of human atheromatous lipid core and fibrous cap of individual advanced atherosclerotic plaques (Stary, Type V) in necropsy samples. Results: The total lipid was of course massively greater in the core than in the cap. The oxidation products, cholest-5-en-3β,26-diol (26-OH-CHOL) and cholest-5-en-3β,7β-diol (7β-OH-CHOL) were detected in all the samples. 26-OH-CHOL was more abundant in the core than in the cap when related both to wet weight and to cholesterol. 7β-OH-CHOL levels were significantly higher in the core than in the cap when related to wet weight but not when related to cholesterol. Because the processing included a sodium borohydride reduction step, the 7β-OH-CHOL detected could partly originate from 7-ketocholesterol or 7-hydroperoxy-cholesterol. Several isomeric hydroxyoctadecadienoic acids were detected in both core and cap, more in the cap when related to cholesterol content. Most of the components of the cap showed a high degree of cross-correlation on linear regression analysis, but cross-correlations were weaker for the core. The core samples contained a larger proportion of linoleate relative to oleate than the fibrous cap. Conclusion: The findings suggest that the different lipid and oxidised lipid contents of cap and core may be due to variations in oxidative activity in different parts of the lesion.