|Title||Altered glycosaminoglycan metabolism in injured arterial wall.|
|Publication Type||Journal Article|
|Year of Publication||1985|
|Authors||Salisbury BG, Hajjar DP, Minick CR|
|Journal||Exp Mol Pathol|
|Date Published||1985 Jun|
|Keywords||Animals, Aorta, Dermatan Sulfate, Endothelium, Female, Glycosaminoglycans, Heparitin Sulfate, Rabbits, Regeneration, Sulfur Radioisotopes, Time Factors, Tritium|
Glycosaminoglycans (GAG) are believed to be important in the pathogenesis of atherosclerosis. We have previously demonstrated that areas of injured aorta that have been re-endothelialized accumulate increased amounts of lipid and GAG when compared to areas remaining de-endothelialized. We have now examined the net incorporation of labeled precursors into the individual GAG present in both re-endothelialized and de-endothelialized areas of rabbit aorta. Aortic tissue was examined at 2-3 and 10-14 weeks after a denuding injury by incubating tissue minces with [3H]glucosamine and sodium [35S]sulfate for 24 hr. Following incubation, the aortic GAG were isolated and assayed for uronic acid concentration and radioactivity. Results indicate that the total GAG concentration was significantly greater (P less than 0.001) in the re-endothelialized (9.46 +/- 0.29 micrograms/mg lipid-free dry residues (LFDR), mean +/- SE) as compared to de-endothelialized (7.89 +/- 0.43 micrograms/mg LFDR) areas. The concentration in uninjured aorta was 9.01 +/- 0.69. The difference between the injured tissues was attributable to increased concentrations of sulfated GAG. Hyaluronic acid and chondroitin sulfate were the most metabolically active of the GAG in either uninjured or injured aorta, together accounting for over 75% of the 3H label. The 3H specific radioactivities of the four GAG in the short-term, re-endothelialized subgroup were all increased nearly twice that found in uninjured and de-endothelialized tissues. With the exception of heparan sulfate, no significant differences were noted in the 3H specific radioactivities between the re-endothelialized and de-endothelialized areas in the long-term subgroup. These results indicate that, relative to adjacent areas of de-endothelialization, GAG preferentially accumulate in re-endothelialized areas even as early as 2-3 weeks following a denuding injury. Overall, metabolic data suggest that increased synthesis is responsible for this effect, although the net contribution of degradative processes cannot be overlooked since GAG turnover was not specifically examined. Thus, it is possible that regenerated endothelium may modify the GAG metabolism of the arterial wall following arterial injury.
|Alternate Journal||Exp Mol Pathol|
|Grant List||HL-07423 / HL / NHLBI NIH HHS / United States |
HL-18828 / HL / NHLBI NIH HHS / United States
HL-31271 / HL / NHLBI NIH HHS / United States
David P. Hajjar, Ph.D.