Proteoglycans have been postulated to play important roles in atherogenesis based in part upon the many studies that have examined alterations in arterial glycosaminoglycans as a function of atherosclerosis. However, our knowledge of the detailed structures and functions of arterial proteoglycans remains limited. Little information is also available on the metabolism of proteoglycans in the arterial wall especially as it is effected by cell-cell interactions that could occur in vivo. Finally, lipoprotein-proteoglycan complexes have been shown to exist in the arterial wall but their potentia role in the genesis of foam cells has not been investigated. The experiments proposed here are directed at: (1) isolating individual proteoglycans from bovine aorta and cultures of bovine aortic endothelial and smooth muscle cells, and characterizing their physico-chemical properties and metabolism, (2) comparing the metabolism of proteoglycans of smooth muscle cells to that of smooth muscle cells co-cultured with endothelial cells or macrophage, and (3) investigating the binding and uptake of lipoprotein-proteoglycan complexes by macrophage and smooth muscle cells. Results of these studies will define physicochemical and metabolic characteristics of individual aortic proteoglycans that may be requisite for fully understanding their role in arterial physiology and atherosclerosis. The proposed studies will also determine if endothelial cells or macrophage are capable of modulating the proteoglycans synthesized by smooth muscle cells. Such a phenomenon could have direct applicability to arterial injury and subsequent repair processes in vivo. Finally, a detailed examination of lipoprotein-proteoglycan complexes and their interactions with macrophage or smooth muscle cells may provide information on the formation of foam cells in vivo indicating a crucial role for arterial proteoglycans in the pathogenesis of atherosclerosis.
| Falcone, D J; Salisbury, B G (1988) Fibronectin stimulates macrophage uptake of low density lipoprotein-heparin-collagen complexes. Arteriosclerosis 8:263-73 |
| Salisbury, B G; Falcone, D J; Minick, C R (1985) Insoluble low-density lipoprotein-proteoglycan complexes enhance cholesteryl ester accumulation in macrophages. Am J Pathol 120:6-11 |
| Salisbury, B G; Hajjar, D P; Minick, C R (1985) Altered glycosaminoglycan metabolism in injured arterial wall. Exp Mol Pathol 42:306-19 |
