Binding of 125I-bFGF to Rat Aortic Smooth Muscle Cells
The proliferation of smooth muscle cells (SMC) in the arterial wall is a key event in the development of atherosclerosis. The locally formed mitogen bFGF is likely to play an important role in initiating and in maintaining the SMC proliferative state. A distinguishing characteristic of bFGF is its strong interaction with the sulfated glycosaminoglycans. In this study the ability of a series of chemically modified heparins and heparan sulfates to compete with the cell surface glycosaminoglycans for 125I-bFGF binding has been investigated. Rat aortic SMC between the 8th and the 18th passage were used. Within the heparin series the order of potency was: Heparin, 6-O-desulfated > 2-O desulfated >> N-acetylated. However, when the activity of the series of heparins for the inhibition of cell growth was assessed, 6-O sulfation was as important as 2-O and N- sulfation. Heparan sulfates gave comparable results. The data presented are consistent with the concepts that: 1) specific structural features are involved in the interaction of SMC glycosaminoglycans with 125I-bFGF, and 2) antimitogenic activity of heparin has structural requirements different than those for bFGF binding.
KeywordsCholesterol Heparin HEPES Cardiol Gelatin
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