Prostaglandins and arterial wall lipid metabolism--in vitro, ex-vivo and in-vivo radioisotopic studies.
It is the aim of this paper to review our findings in vitro, in experimental animals and in human on arterial wall lipid metabolism. Radiolabelling of LDL indicates that experimentally induced lesions in hypercholesterolemic rabbits do show less lipid accumulation if treated with prostaglandins (PGI2, PGE1, 13,14-dihydro-PGE1) or stimulators of prostaglandin synthesis (isradipine, a calcium channel blocker of the dihydropyridine family). Endogenous blockade of cyclooxygenase by ASA-pretreatment results in a complete abolishing of this apparently PG-mediated benefit. In-vivo studies using autologous 123I-labeled LDL without therapeutic intervention exhibit a quite good reproducibility of the imaging technique. While PGE1 (at 2 different therapeutic regimens) is inducing lipid lesion regression, the comparable benefit induced by isradipine again disappears with concomitant ASA-therapy. Quantitative estimation of arterial wall lipid metabolism in patients undergoing vascular surgery demonstrates that PGI1- (and cAMP-) increase are paralleled by a several-fold increase of acid and neutral cholesterol ester hydrolase and a decrease in net arterial cholesterol ester content. This benefit again disappears with concomitant ASA-therapy. These findings are allowing to conclude that (exogenously added or endogenously stimulated) prostaglandins do significantly improve arterial wall lipid metabolism.
Sinzinger
H
H
Wilhelm Auerswald Atherosclerosis Research Group, Vienna, Austria.
Rogatti
W
W
D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000378:metabolism*; D001241:Aspirin / Q000494:pharmacology; D002784:Cholesterol / Q000378:metabolism; D000242:Cyclic AMP / Q000097:blood; D011464:Epoprostenol / Q000097:blood; D006801:Humans; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D017275:Isradipine / Q000494:pharmacology; D007700:Kinetics; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D011448:Prostaglandin Antagonists; D011453:Prostaglandins / Q000494:pharmacology*; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology; D011817:Rabbits
D007457:Iodine Radioisotopes; D008055:Lipids; D008077:Lipoproteins, LDL; D011448:Prostaglandin Antagonists; D011453:Prostaglandins; D011459:Prostaglandins E, Synthetic; D002784:Cholesterol; D011464:Epoprostenol; D000242:Cyclic AMP; D000527:Alprostadil; D001241:Aspirin; D017275:Isradipine