The Relationship Between Plasma and Tissue Lipids in Human Atherosclerosis

Smith, E. B.

doi:10.1016/b978-0-12-024912-1.50008-9

Cited by 323 publications

(107 citation statements)

References 95 publications

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“…As expected, the CE content also increased with increasing lesion severity, although the CE load per cholesterol in lesion lipoproteins tended to decrease in the most advanced lesions. This is consistent with an earlier report showing a decrease in C18:2 in fibrous plaques, 30 as CE measured herein represents the sum of C18:2 and cholesteryl arachidonate. This suggests increased hydrolysis of lipoprotein CE in advanced lesions and/or preferential loss of CE rather than cholesterol from lipoproteins.…”

Section: Discussionsupporting

confidence: 82%

Disease Stage-Dependent Accumulation of Lipid and Protein Oxidation Products in Human Atherosclerosis

Upston

Niu

Brown

et al. 2002

The American Journal of Pathology

126

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Oxidative modification of low-density lipoprotein is thought to promote arterial lipid accumulation and atherogenesis. Previous studies reported on the presence of certain lipid or protein oxidation products in lesions, although a systematic investigation measuring several oxidation parameters and the accumulation of nonoxidized lipids and antioxidants at various stages of atherosclerosis has not been performed in the same tissue. Using the intimal lipoprotein-containing fraction of human aortic lesions, we demonstrate here that cholesterol accumulated with lesion development and that this increase was already significant at the fatty streak stage. By comparison, cholesterylesters increased significantly only in fibrofatty and more complex lesions that also contained significantly increased amounts of cholesterylester hydro(pero)xides and 27-hydroxycholesterol. Cholesterylester hydroxides were the major lipid oxidation product detected. Despite accumulation of oxidized lipid, ␣-tocopherol was also present and maintained at a comparable level over the disease process. Of the oxidized protein moieties measured only o,o-dityrosine increased with disease, although chlorotyrosines were present at relatively high levels in all lesions compared to healthy vessels. Our data show that accumulation of nonoxidized lipid precedes that of oxidized lipid in human aortic lesions. The development of atherosclerosis to clinical manifestations is a protracted process that spans several decades. It is well established that lipids, specifically cholesterol, accumulate as the disease progresses 1 and that these lipids are derived from plasma low-density lipoprotein (LDL). Aberrant uptake of LDL and its associated lipids by intimal monocytes that have infiltrated from the blood is believed to generate foam cells and thereby initiate atherosclerosis. 2 Foam cells are the hallmark of the fatty streak/early lesion from which the more advanced and complicated lesions derive. In advanced lesions, a fibrous cap is formed from collagen and a lipid-rich necrotic core. Vessel lumen narrowing because of the enlarged fibrous cap and plaque rupture lead to clinical manifestations.The definitive mechanisms leading to the initiation and development of atherosclerosis are unknown. However, retention of LDL in the vessel wall because of interaction and complex formation with extracellular matrix components is well-documented 3 and is thought to be important. Further, a bulk of evidence suggests that oxidative modifications to LDL contribute to its retention. 4 -6 Both arterial wall retention and oxidative modification of LDL are thought to contribute to foam cell formation.In vitro studies with plasma LDL have shown that oxidative modifications proceed in different stages and involve changes to LDL's antioxidants, lipids, and protein components. The nature and extent of these alterations vary depending on the type of oxidant involved, the oxidant to lipoprotein ratio used, and the extent to which oxidation is allowed to proceed. Originally 4 the pa...

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Section: Discussionsupporting

confidence: 82%

Disease Stage-Dependent Accumulation of Lipid and Protein Oxidation Products in Human Atherosclerosis

Upston

Niu

Brown

et al. 2002

The American Journal of Pathology

126

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“…However, as shown in our present study, minces gave apoB values which were 3 times lower than those of homogenates. Smith and Slater 28 "" 31 expressed their values in terms of LDL-cholesterol. When converted into LDL-apoB, their values from minces were about x li of the values recorded in our present study using homogenates.…”

Section: Discussionmentioning

confidence: 99%

“…By use of this procedure the buffer-soluble apoB content in the intima of the grossly normal human aorta was determined and shown to range in value between 0.34 age (years) FIGURE 31 used whole minces of human aortic intima which were inserted directly into the gel of the EID system. However, as shown in our present study, minces gave apoB values which were 3 times lower than those of homogenates.…”

Section: Discussionmentioning

confidence: 99%

Quantification of apolipoprotein B in grossly normal human aorta.

Hoff

Heideman

Gaubatz

et al. 1977

Circulation Research

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A quantitiative electroimmunodiffusion (EID) assay was developed for apolipoprotein B (apoB), the major apoprotein of human plasma low density lipoproteins (LDL) and very low density lipoproteins (VLDL). Specificity, sensitivity (30-200 ng) and reproducibility (11%) were established. We used this system to determine the amount of buffer-soluble apoB in supernatant fractions from homogenates of the intima from grossly normal human aortas. Assays of whole tissue minces yielded only one-third of the apoB in supernatant fractions. Intimal homogenates contained 0.34-18.45 mug of apoB/mg of tissue, dry weight (mean 5.42 +/- 3.95 SD). We also found that no apoB was detected in the homogenates of adjacent tunica media. Furthermore, most of the intimal apoB was found in the LDL density (d) fraction (d 1.006-1.063) after differential ultracentrifugation, while the VLDL (d less than 1.006) fraction contained only negligible amounts of apoB. By electron microscopy, it was determined that the LDL density fraction contained particles 200-250 A in diameter which were similar in size to plasma LDL. These results suggest that grossly normal aortas contain significant quantities of intact LDL.

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“…There was a lack of agreement in earty studies of human arteries concerning whether there was a similarity in plasma and arterial cholesteryl esterfatty acid composition. 49 The studies of Smith 50 demonstrated that this discrepancy may have been due to the type of lesion being analyzed. She showed that the fatty streak composed predominantly of foam cells with very little extracellular lipid had a higher content of cholesteryl oleate than did plasma.…”

Section: Plasma Llpid Composition Determines Aortic Llpid Compositionmentioning

confidence: 99%

Lipid composition of aorta of Watanabe heritable hyperlipemic and comparably hypercholesterolemic fat-fed rabbits. Plasma lipid composition determines aortic lipid composition of hypercholesterolemic rabbits.

et al. 1988

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Aortic and plasma lipid compositions were compared during a 12-month period in Watanabe heritable hyperlipemic (WHHL), comparably hypercholesterolemic fat-fed, and age-matched control normolipidemic rabbits to determine whether exposure to equivalent degrees of endogenous or exogenous hypercholesterolemia led to differences in the composition and concentration of lipids deposited in the artery wall. Although there were marked differences in the distribution of cholesterol among the Iipoproteins in the WHHL versus the fat-fed rabbits, the contents of both free and esterified cholesterol were elevated to an equivalent degree in the aorta and plasma. In contrast, the trigiyceride content of both the plasma and aorta were elevated only in the WHHL rabbits. However, aortic total phospholipids were increased in both the WHHL and fat-fed animals as compared to control rabbits. In the control rabbits, there was an agedependent enrichment in aortic relative to plasma cholesteryl-oleate consistent with low density Iipoprotein (LDL) receptor-directed intracellular cholesteryl ester processing. In contrast, enrichment in cholesteryloleate in aortae relative to plasma was not detected in either WHHL or fat-fed groups, suggesting that the plasma cholesteryl ester composition was the primary determinant of the aortic cholesterol composition. Thus, during chronic hypercholesterolemia, deposition of lipids in the artery wall appears to be determined by plasma Iipoprotein levels and composition if the LDL receptor is either absent on a genetic basis or suppressed due to a high-fat, high-cholesterol diet. E arly studies focusing on the lipid composition of the atherosclerotic plaque in fat-fed rabbits demonstrated increases in free and esterified cholesterol and phospholipids.1 -4 The arterial lipid composition was similar to that in plasma, suggesting that it was derived from the plasma. 56 The source of the increased arterial lipids in rabbits, swine, and humans has now been clearly demonstrated to be the plasma Iipoproteins, 7 -15 in particular low density Iipoproteins (LDL). However, to date the role played by Iipoprotein receptors in directly influencing lipid deposition and composition in the artery wall is unclear.The Watanabe heritable hyperlipemic rabbit (WHHL) is an animal model of homozygous familial hypercholesterolemia. 18 . 17 rabbits exhibit massive hypercholesterolemia and moderate hypertriglyceridemia 20 and develop extensive lesions of atherosclerosis. 21 The hypercholesterolemia in rabbits that results from cholesterol feeding also leads to the formation of atherosclerotic lesions and may lead to down-regulation in the number of functional LDL receptors. 22 This study examines the composition of both arterial wall and plasma lipids in WHHL, comparably hypercholesterolemic fat-fed (FF), and age-matched control rabbits to determine whether a reduction in the number of functional LDL receptors influences the amount and type of lipids deposited in the arteries during chronic hypercholesterolemia. Methods Rabbit Co...

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The Relationship Between Plasma and Tissue Lipids in Human Atherosclerosis

Cited by 323 publications

References 95 publications

Disease Stage-Dependent Accumulation of Lipid and Protein Oxidation Products in Human Atherosclerosis

Disease Stage-Dependent Accumulation of Lipid and Protein Oxidation Products in Human Atherosclerosis

Quantification of apolipoprotein B in grossly normal human aorta.

Lipid composition of aorta of Watanabe heritable hyperlipemic and comparably hypercholesterolemic fat-fed rabbits. Plasma lipid composition determines aortic lipid composition of hypercholesterolemic rabbits.

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