Glycosaminoglycan fractions from human arteries presenting diverse susceptibilities to atherosclerosis have different binding affinities to plasma LDL.

Abstract

The topographic distribution of atherosclerotic lesions is influenced by biochemical factors intrinsic to the arterial wall. In the present work we have investigated whether the composition/chemical structure of glycosaminoglycans constitutes one of these factors. Normal human arteries were obtained at necropsy, and in order of decreasing susceptibility to atherosclerosis, consisted of the abdominal and thoracic aortas and the iliac and pulmonary arteries. The results showed similar concentrations of total glycosaminoglycan and collagen. Of the glycosaminoglycans known to interact with low-density lipoprotein (LDL), dermatan sulfate was present in all arteries in comparable concentrations, but the aortas had a 30% higher content of chondroitin 4/6-sulfate, which in turn was slightly enriched in 6-sulfated disaccharide units. LDLaffinity chromatography with dermatan sulfate+chondroitin 4/6-sulfate fractions demonstrated that increasing affinity to LDL matched an increasing susceptibility to atherosclerosis. Analysis of glycosaminoglycans in the eluates indicated a positive correlation between affinity to LDL and increasing molecular weight and the existence of a fraction of glycosaminoglycans of high affinity to LDL in the aortas only. These results suggest that arterial glycosaminoglycans participate in the multifactorial mechanisms that modulate the differential localization of atherosclerotic lesions. 1 However, factors intrinsic to the arterial bed and its bloodcarrying functions also influence the occurrence of lesions. The primary evidence came from morphological study of necropsy material, which demonstrated that the incidence and/or severity of atherosclerotic lesions differed as a function of anatomic location.2 -3 Additionally, these studies revealed that in affected arteries, lesions tended to be located at critical sites, such as the entrances of vessels and flow dividers, where the effects of fluid turbulence would be more pronounced. Experimental physiological investigations have supported these findings 68 and have shown that the shear force due to blood circulation, chiefly at arterial pressures, is an important cause of endothelial dysfunction at these sites. 9 Still, arterial geometry and pressure are not sufficient to explain the localization of lesions, since major areas of high risk for atherosclerosis also occur away from the ostia and bifurcations 10 and some arteries subjected to normal arterial blood pressure are little affected by atherosclerosis. and the activity of acid cholesterol esterase 14 vary among vessels, and this variation could be related to differences in atherosclerosis susceptibility. A further aspect of arterial constitution that has been correlated with regional differences in the incidence of atherosclerosis is the degree of folding of the internal elastic membrane in humans, 15 which somehow reflects the amount of elastin in the vessel wall.Taken together, the results of these mostly recent studies show that focal metabolic and biochemical factors inherent in...

Lysophosphatidylcholine Regulates Synthesis of Biglycan and the Proteoglycan Form of Macrophage Colony Stimulating Factor

“…35 7-KC and lysoPC regulate chain elongation on all of the major secreted proteoglycan species. This may be functionally significant, because longer chains are correlated with increased LDL binding, 25,31 and these compounds did indeed stimulate synthesis of proteoglycans with enhanced lipoprotein-binding properties. The ability of both compounds to cause chain elongation suggests nonspecific regulation, perhaps attributable to increases in the amount/activity of the enzymes responsible for chain synthesis.…”

“…25,31 Therefore, the LDL-binding properties of proteoglycans synthesized in the presence of lysoPC were evaluated (Figure 4). Because of the finding that the ratio of small proteoglycans is altered by lysoPC, we chose to focus on peak 2 in this assay.…”

Unique Extracellular Matrix Heparan Sulfate from the Bivalve Nodipecten nodosus (Linnaeus, 1758) Safely Inhibits Arterial Thrombosis after Photochemically Induced Endothelial Lesion

“…Heparan sulfate from human aorta was extracted and purified as described previously (18 (Rockville, MD). Agarose (standard low M r ) was obtained from Bio-Rad; toluidine blue and alcian blue were from Fisher; human antithrombin, human factor Xa, and thrombin were from Hematologic Technologies Inc.; thrombin chromogenic substrate tosyl-Gly-Pro-Arg-p-nitroanilide acetate (Chromozyn TH) and factor Xa chromogenic substrate N-methoxycarbonyl-D-norleucyl-glycyl-L-arginine-4-nitranillide-acetate were from Amersham Biosciences.…”

Age-Related Changes in Populations of Aortic Glycosaminoglycans

“…It is known that certain glycosaminoglycan species, including particular populations of a given species, have greater affinity for LDL. 6,11,16 The occurrence of atherosclerotic lesions is associated with a number of risk factors, such as elevated serum lipoprotein levels, hypertension, smoking, gender, and family history. 17 However, intrinsic factors of the arterial bed and its bloodcarrying functions also influence the occurrence of lesions.…”

“…[1][2][3][4][5][6][7][8][9][10][11] This is a step in the normal exchange of components between the circulating plasma and the arterial wall. However, during atherosclerosis, this process contributes to continuous focal deposition of cholesterol-rich lipoproteins, mainly LDL, in lesions.…”