We compared the glycosaminoglycan content of human venous and arterial walls. The most abundant glycosaminoglycan in human veins is dermatan sulfate whereas chondroitin 4/6-sulfate is preponderant in arteries. The concentrations of chondroitin 4/6-sulfate and heparan sulfate are approximately 4.8- and approximately 2.5-fold higher in arteries than in veins whereas dermatan sulfate contents are similar in the two types of blood vessels. Normal and varicose saphenous veins do not differ in their glycosaminoglycan contents. It is known that certain glycosaminoglycan species from the arterial wall, mainly high-molecular-weight fractions of dermatan sulfate+chondroitin 4/6-sulfate have greater affinity for plasma LDL. These types of glycosaminoglycans can be identified on a LDL-affinity column. We now demonstrated that a similar population of glycosaminoglycan also occurs in veins, although with a lower concentration than in the arteries due to less chondroitin 4/6-sulfate with affinity for LDL. The concentrations of dermatan sulfate species, which interact with LDL, are similar in arteries and veins. The presence of these glycosaminoglycans with affinity to plasma LDL in veins raises interesting questions concerning the role of these molecules in the pathogenesis of atherosclerosis. Possibly, the presence of these glycosaminoglycans in the vessel wall are not sufficient to cause retention of LDL and consequently endothelial dysfunction, but may require additional intrinsic factors and/or the hydrodynamic of the blood under the arterial pressure.

Abstract-Glycosaminoglycans were extracted from the intima and media layers of normal human thoracic aortas from donors of different ages. The arterial segments were devoid of macroscopically visible lesions obtained from patients who had no clinically evident cardiovascular disease. Total glycosaminoglycan content increases during the first 40 years of life. Changes in the content of hyaluronic acid and heparan sulfate are less noticeable. The content of chondroitin sulfate (mainly the 6-isomer) increases, whereas dermatan sulfate remains constant. Plasma LDL-affinity chromatography of dermatan sulfateϩchondroitin 4/6-sulfate fractions allowed the separation of LDL high-and low-affinity glycosaminoglycan species. Remarkably, only glycosaminoglycan species with low affinity for plasma LDL increase with age in the disease-free areas of human thoracic aortas studied. These results suggest that age-related changes in glycosaminoglycan composition of the arterial wall do not contribute to increased deposition of plasma LDL. However, the alternative explanation that individuals with arterial glycosaminoglycans that avidly bind LDL would develop early and severe cardiovascular disease and would thus be excluded from our analysis cannot be ruled out.(Arterioscler Thromb Vasc Biol. 1998;18:604-614.)Key Words: glycosaminoglycans Ⅲ chondroitin sulfate Ⅲ dermatan sulfate Ⅲ atherosclerotic risk factor Ⅲ LDL G lycosaminoglycan chains that project from proteoglycans of the arterial wall are responsible for the formation of complexes with plasma LDL. [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.12-14 In turn, glycosaminoglycan-LDL complexes are more easily internalized by macrophages than LDL alone, 15 thereby enhancing the formation of foam cells. Also, glycosaminoglycans induce structural alterations in LDL molecules that may potentiate their atherogenic effects.9 Therefore, the nature of the glycosaminoglycan-LDL interaction has been extensively studied. 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. The primary evidence for this influence comes from morphological studies of necropsy material, showing that the incidence and/or severity of atherosclerotic lesions varies as a function of anatomical location. 18 -21 We have demonstrated that glycosaminoglycans from different locations vary in composition and in binding affinity for plasma LDL.11 These results suggested that glycosaminoglycan c...

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