Glycosaminoglycans and apolipoproteins B and A-I in human aortas. Chemical and immunological analysis of lesion-free aortas from children and adults.

Abstract

To study changes In the contents of plasma llpoprotelns In human arteries with age and the relationship of llpoprotelns with other arterial constituents, we analyzed the contents of apolipoproteins B (apo B) and A-l (apo A-l), free and esterifled cholesterol, and glycosaminoglycans (GAG) In lesion-free aortic Intlmas of 30 children and adults. The content of apo B Increased significantly with age, whereas that of apo A-l remained relatively constant. Apo B and apo A-l had significant positive correlations with the content of chondroltln sulphates A+C (CS A+C), which comprised 35% to 47% of the aortic GAG. The correlations remained significant after correction for the effect of age. Aortic apo B, but not apo A-l, also showed significant positive correlations with the contents of Intimal free and esterified cholesterol. The results Indicate that: 1) considerable amounts of apo B and apo A-) can be found in lesion-free aortic Intlmas; 2) there Is an age-related rise In the content of apo B and a fall In the ratio of apo A-l to apo B, which are unfavorable developments In the light of current views on atherogenesls; 3) the contents of the apolipoproteins are proportional to that of CS A+C, which might have a role In the retention of llpoprotelns In the arteries. (Arteriosclerosis 7:333-340 July/August 1987)A therogenesis is a slow process beginning early in life: fatty streaks appear in human aortas during the first, and fibrous plaques, during the second decade of life.1 The most conspicuous features of atherosclerosis are the proliferation of arterial smooth muscle cells and the accumulation of lipoproteins, extra-and intracellular lipids, and connective tissue.2 Although the sequence of the pathogenic events is obscure, several studies indicate the importance of the accumulation of low density lipoproteins (LDL) in the arterial wall as one of the initial changes.3 ' 4 Several authors 3 " 12 have studied the amount of lipoproteins in adult arteries, but only scattered data 34 are available on the concentration of apolipoproteins in the aortas of children and adolescents.In order to reach arterial cells, lipoproteins and other plasma constituents must diffuse through a subendothelial extracellular matrix composed mainly of collagen, elastin, and glycosaminoglycans (GAG). It is possible that the ma- trix components affect the passage and metabolism of lipoproteins. GAG can retain LDL in the arterial wall by means of either molecular sieving or complex formation. 13Indeed, GAG-LDL complexes have been identified in atherosclerotic arteries 14 and there is a close topographic relationship between arterial GAG and immunoreactive apo B in human and swine arteries.1516 There is also a positive correlation between the contents of GAG and LDL-derived cholesteryl esters in the coronary artery intima-medias of children. 17As far as the authors know, no data are available on the relationship between the contents of apolipoproteins and different GAG in human arteries. The purpose of the present study was: 1) to analyze the chan...

Childhood Levels of Serum Apolipoproteins B and A-I Predict Carotid Intima-Media Thickness and Brachial Endothelial Function in Adulthood

“…A high apoB/apoA-I ratio indicates the number of atherogenic lipoprotein particles, which are likely to be deposited in the arterial wall. In line, we have previously shown an age-related increase in the content of apoB and a decrease in the apoA-I/apoB ratio in the lesion-free aortic intimas of children and adolescents, changes that could favor the deposition of lipids in the arteries (33).…”

Role of Oxidative Modifications in Atherosclerosis

“…The retention of lipoproteins within the arterial wall, however, appears tightly linked to components of the extracellular matrix. Apolipoprotein B-100, the single protein associated with LDL, is retained within the arterial wall in close association with arterial proteoglycans (118,1091). This interaction is mediated by specific residues (3359 -3369) (71) that, when mutated, protect experimental animals against the development of atherosclerosis (71,857).…”

Lipoprotein-Associated Phospholipase A 2 , Platelet-Activating Factor Acetylhydrolase, Is Expressed by Macrophages in Human and Rabbit Atherosclerotic Lesions

“…Even though Lp-PLA 2 can be anti-inflammatory under certain conditions, such as in a rat foot pad model after exogenous PAF application, 20 lyso-PC and free oxidized fatty acids in atherosclerotic lesions can substantially amplify the pathological process and cause chronic monocyte/macrophagedominated inflammation, which is typical of atherosclerosis, in view of the fact that the arterial wall contains much higher concentrations of LDL than most other physiological compartments. 45,46 Increased expression of Lp-PLA 2 in lesion macrophages suggests that modulation of the enzyme activity could become a potential target for the development of antiatherogenic therapy in the vessel wall.…”