Mapping of proteoglycans in atherosclerotic lesions

Abstract

The involvement of sulphated glycosaminoglycans in atherosclerotic changes have been studied in human and rat arteries, and biochemical experiments have revealed that a significant increase in the contents of chondroitin sulphate/dermatan sulphate and cholesterol, but loss of heparan sulphate, occurs in human atherosclerotic arterial tissues. Electron micrographs have revealed that extracellular deposits of lipid are predominantly present in areas rich in chondroitin sulphate proteoglycans but not in areas rich in collagen bundles and dermatan sulphate proteoglycans. The different types of proteoglycans have been distinguished in situ by the cuprolinic blue staining method and enzymatic degradation experiments, and their topohistochemical distribution patterns analysed by morphometry of proteoglycan/cuprolinic blue precipitates. The ultracytochemical investigations indicate changes in size and pattern of chondroitin sulphate-rich proteoglycan-cuprolinic blue precipitates in human atherosclerosis. In plaque tissue, these precipitates are significantly enlarged. In addition, they accumulate around smooth muscle cells in the medial tissue. An increase in the size of proteoglycan-cuprolinic blue precipitates has also been observed in balloon catheter-induced lesions in rat carotid arteries. The large chondroitin sulphate as well as the small dermatan sulphate proteoglycan-cuprolinic blue precipitates show this alteration 2 weeks after balloon injury. We suggest that quantitative and qualitative alterations in the arterial proteoglycans occur in the pathogenesis of atherosclerosis in addition to the cell proliferation and lipid accumulation.

Ultrastructural Localization of Secretory Type II Phospholipase A 2 in Atherosclerotic and Nonatherosclerotic Regions of Human Arteries

“…Fig 4 shows a typical section in which immunogold particles were also detected and found to be associated with other ECM components localized close to the cells. 38 In lipid-rich regions, snpPLA 2 was detected in areas containing large, extracellular lipid droplets as shown in Fig 5. Intracellularly, immunogold particles were found in the cytoplasm of SMCs and on electron-dense vesicles (Figs 2 and 3A). In nonatherosclerotic tissues, we observed a weak pattern of extracellular gold particles in the ECM (Fig 6).…”

“…These types of proteoglycan mainly contain chondroitin sulfate and dermatan sulfate GAG chains. 38 We reported previously the capacity of snpPLA 2 to interact with the GAG moiety of proteoglycans synthesized by human arterial SMCs.33 It will be interesting to further investigate whether snpPLA 2 around collagen fibers binds directly to collagen or through the chondroitin sulfate or dermatan sulfate GAG chains of small proteoglycans, like decorin or biglycan, which are known to be part of the collagen network organization in the arterial wall. [52][53][54] The interaction between decorin or biglycan and collagen type I has been studied extensively in vitro and in vivo.…”

A definition of the intima of human arteries and of its atherosclerosis-prone regions. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association.

“…In normal human coronary arteries, the contents of dermatan sulfate and chondroitin sulfate increase with age. 169 Based on topographical distribution of proteoglycan types in normal human aortic media, Volker et al 170 described dermatan sulfate proteoglycan associated with collagen fibers, heparan sulfate proteoglycan associated with elastic fibers as well as the surfaces of smooth muscle cells, and chondroitin sulfate proteoglycan in the extracellular space.…”

Apolipoprotein E Containing High Density Lipoprotein Stimulates Endothelial Production of Heparan Sulfate Rich in Biologically Active Heparin-like Domains

“…The age-dependent decrease in HS is more pronounced in atherosclerotic tissues than in normal tissues (10,11). An inverse correlation between the amount of cholesterol in the lesion and the concentration of HS was observed in human aortas.…”

“…A reduction in arterial HS and heparin has been observed under conditions of inflammation and atherosclerosis as well as with increased age (6 -14). The age-dependent decrease in HS is more pronounced in atherosclerotic tissues than in normal tissues (10,11). An inverse correlation between the amount of cholesterol in the lesion and the concentration of HS was observed in human aortas.…”