Injury to the arterial wall of rabbits produces proteoglycan variants with 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 culture system, PG were isolated under dissociative conditions from deendothelialized 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 35S-label into proteoglycans than control tissues. Ion-exchange chromatography of PG from DEA and REA tissues yielded PG-I, PG-II, and PG-III, while from control tissue only PG-I and PG-II. PG-II formed major portion (74-84%) of the isolated PG in all three tissue types. PGI preparations comprised entirely of heparan sulfate (HS)-PG of similar hydrodynamic size (Kav = 0.45-0.47). PG-II from DEA and REA tissues consisted of PGII-A (Kav = 0.02-0.04) and PGII-B (Kav = 0.32), while PG-II from control tissue contained only PGII-B with relatively smaller hydrodynamic size (Kav = 0.40). PGII-A preparations contained predominantly chondroitin sulfate (CS)-PG with no dermatan sulfate (DS); whereas PGII-B consisted mainly of CS/DS-PG, with relatively high proportion of DS in DEA and REA tissues vs. control tissue (50-54% vs. 43%). Further, the glycosaminoglycan 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 and 20% HS-PG; CS/DS-PG was similar to those found in PGII-B from DEA and REA tissues. HS-PG from PG-II and PG-III, unlike those from PG-I, was enriched with N-sulfated residues. PGI from all the three tissue types 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 injury with or without regenerated endothelium produces proteoglycan variants with altered characteristics and enhanced LDL-binding ability.
Department of Applied Health Sciences, Tulane University Medical Center School of Public Health and Tropical Medicine, New Orleans, LA 70112-2824.
S R
SR
Srinivasan
J H
JH
Xu
P
P
Vijayagopal
B
B
Radhakrishnamurthy
G S
GS
Berenson
D000818:Animals; D001011:Aorta; D002846:Chromatography, Affinity; D002850:Chromatography, Gel; D004730:Endothelium, Vascular / Q000293:injuries* / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D011509:Proteoglycans / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D011817:Rabbits; D011973:Receptors, LDL / Q000032:analysis* / Q000378:metabolism
D006025:Glycosaminoglycans; D008077:Lipoproteins, LDL; D011509:Proteoglycans; D011973:Receptors, LDL