INJURY TO THE ARTERIAL-WALL OF RABBITS PRODUCES PROTEOGLYCAN VARIANTSWITH ENHANCED LOW-DENSITY LIPOPROTEIN-BINDING PROPERTY

The effect of arterial injury on proteoglycans (PG) and their ability to bind low-density lipoprotein (LDL) were studied in rabbits 12 weeks after balloon injury. Following biosynthetic labeling in an organ cul ture system, PG were isolated under dissociative conditions from deend othelialized areas (DEA), reendothelialized areas (REA), and uninjured areas (control) of the aortic tissue. DEA and REA tissues yielded 42- 52% more PG and incorporated- 39-67% more S-35-label into proteoglycan s than control tissues. Ion-exchange chromatography of PG from DEA and REA tissues yielded PG-I, PG-II, and PG-III, while from control tissu e only PG-I and PG-II. PG-II formed major portion (74-84%) of the isol ated PG in all three tissue types. PGI preparations comprised entirely of heparan sulfate (HS)-PG of similar hydrodynamic size (K(av) = 0.45 -0.47). PG-II from DEA and REA tissues consisted of PGII-A (K(av) = 0. 02-0.04) and PGII-B (K(av) = 0.32), while PG-II from control tissue co ntained only PGII-B with relatively smaller hydrodynamic size (K(av) = 0.40). PGII-A preparations contained predominantly chondroitin sulfat e (CS)-PG with no dermatan sulfate (DS); whereas PGII-B consisted main ly of CS/DS-PG, with relatively high proportion of DS in DEA and REA t issues vs. control tissue (50-54% vs. 43%). Further, the glycosaminogl ycan chains of CS/DS-PG from DEA and REA tissues were 1.7-fold longer than those from control tissue. PG-III contained about 80% CS/DS-PG an d 20% HS-PG; CS/DS-PG was similar to those found in PGII-B from DEA an d REA tissues. HS-PG from PG-II and PG-III, unlike those from PG-I, wa s enriched with N-sulfated residues. PGI from all the three tissue typ es bound, poorly to LDL. On the other hand, PGII-A, PGII-B, and PG-III -from DEA and REA tissues showed enhanced ability to bind LDL, in that order. For example the LDL-binding ability of PGII-B from DEA and REA was 2.9- to 3.1-fold above that from control tissue. Thus, arterial i njury with or without regenerated endothelium produces proteoglycan va riants with altered characteristics and enhanced LDL-binding ability.