The incidence of cardiovascular diseases increases significantly with age. Regrettably, the understanding of the pathogenesis of these age-associated diseases is poor at present. Several lines of evidence indicate that vascular endothelial cell-associated proteoglycans represent key elements for important vessel functions that include: antithrombotic activity; fluid and electrolyte exchanges; lipid/lipoprotein transport and accumulation; modulation of medial smooth muscle cell proliferation; and others. Accordingly, we plan: a) to identify the classes and the structure of proteoglycans synthesized by cultured vascular endothelial and smooth muscle cells and possible asymmetrical distributions of proteoglycans; b) to determine the rates of proteoglycan synthesis and degradation in endothelial cells; c) to establish whether alterations of proteoglycan structure and/or metabolism accompany the aging of endothelial cells in vitro; and d) to determine whether young or senescent endothelial cells modulate proteoglycan homeostasis in smooth muscle cells via soluble metabolites. The experimental procedures will include gel and paper chromatography, electrophoresis, isopycnic density centrifugation, enzymatic treatments, peptide mapping, pulse- chase protocols, and others. The research lines proposed here will clarify: some key mechanisms of proteoglycan regulation in vascular wall cells; relative interactions between endothelial cells and smooth muscle cells; and possible alterations in these functions during aging in vitro. The resulting information will be of great importance to identify potential, basic defects in vascular homeostasis that may underlie certain pathological conditions, and, or this basis, will contribute to design fucture interventions on the process of vascular pathogenesis associated with aging.
