13-hydroxy-9-11-octadecadienoic-acid and cholest-5-ene-3-beta-26-diol

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.. 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.. The total lipid was of course massively greater in the core than in the cap. The oxidation products, cholest-5-en-3beta,26-diol (26-OH-CHOL) and cholest-5-en-3beta,7beta-diol (7beta-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. 7Beta-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 7beta-OH-CHOL detected could partly originate from 7-ketocholesterol or 7-hydroperoxycholesterol. 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.. 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.

Topics: Aged; Aged, 80 and over; Arteriosclerosis; Cholesterol; Chromatography, Gas; Fatty Acids; Humans; Hydroxycholesterols; Linoleic Acids; Linoleic Acids, Conjugated; Lipid Metabolism; Lipids; Male; Mass Spectrometry

Lipids and oxidised lipids were analysed by GC and GC-MS in human necropsy samples of normal artery and individual atherosclerotic lesions, from aorta and common carotid artery, including fatty streaks, intermediate lesions and advanced lesions. Age-related increases were seen for linoleate, oleate and cholesterol in normal artery, but not in lesions. Each category of lesion was much richer than normal artery in all the lipids measured and in oxidised lipids (oxysterols and hydroxyoctadecadienoic acids), although a degree of overlap existed between the compositions of the various categories of lesion. 26-Hydroxycholesterol and 7 beta-hydroxycholesterol levels were extremely low or undetectable in normal artery, but significantly higher in each of the categories of lesions. The generally wide variation in lipid composition of individual lesions within each category, and the fact that a few individual lesions showed no detectable 26-hydroxycholesterol or 7 beta-hydroxycholesterol, suggested that the lipid oxidation in lesions and therefore perhaps the progression of lesions may be intermittent. Fatty streaks showed the highest concentration of 7 beta-hydroxycholesterol relative to cholesterol, and the lowest ratio of linoleate to oleate, suggesting that this type of lesion experiences the greatest concentration of free radical activity. Levels of the enzymatic product 26-hydroxycholesterol were approximately proportional to cholesterol in all the categories of lesions. 26-Hydroxycholesterol was significantly more abundant in advanced lesions than in intermediate lesions or fatty streaks. 26-Hydroxycholesterol levels were higher in macrophage-rich intermediate and advanced lesions than in their fibrous counterparts. This distinction between macrophage-rich and fibrous lesions was also true for most of the other lipid components, consistent with the involvement of macrophages in lipid accumulation, lipid oxidation and lesion development.

Topics: Aging; Arteries; Arteriosclerosis; Chromatography, Gas; Gas Chromatography-Mass Spectrometry; Humans; Hydroxycholesterols; Linoleic Acids; Lipid Metabolism; Oxidation-Reduction

Lipids and oxidised lipids were analysed by GC and GC-MS in samples of human atheroma (necrotic gruel from the interior of advanced atherosclerotic plaques in the aorta) and human normal aorta (lesion-free intima plus inner media) from necropsy subjects. Cholest-5-en-3 beta,26-diol and cholest-5-en-3 beta,7 beta-diol were detected in all the atheroma samples examined but not in significant amounts in normal aorta. In atheroma, cholest-5-en-3 beta,26-diol was approximately proportional to cholesterol. Several isomeric hydroxy-octadecadienoic acids were detected in atheroma, and, in smaller amounts, in normal aorta. Many of the components of atheroma showed a high degree of cross-correlation on linear regression analysis, whilst cross-correlations were somewhat weaker for normal aorta. Atheroma showed a vast accumulation of lipid, especially cholesterol, in comparison to normal aorta. The atheroma samples contained a larger proportion of linoleate relative to oleate than the normal aorta. Levels of fatty acids relative to cholesterol were lower for atheroma than for normal aorta. The chemical composition of atheroma appeared unrelated to the age of the subject, whereas age-related increases in linoleate, oleate and cholesterol content were seen in the samples of normal aorta.

Topics: Age Factors; Aorta; Arteriosclerosis; Fatty Acids; Gas Chromatography-Mass Spectrometry; Humans; Hydroxycholesterols; Linoleic Acids; Lipids; Oxidation-Reduction