Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The release and the local activity of plasminogen activator (PA) were studied in isolated perfused dog hearts, without or with intimal injury induced by means of a balloon catheter inserted into the left anterior descending coronary artery (LAD). Thrombin but not DFP-thrombin induced a dose-dependent PA release in doses of 8 to 32 units. ADP 20 or 200 mumol but not ergonovine 20 or 200 micrograms induced a weak PA release. The local PA activity was much lower in the LAD at 1 or 4 weeks after this injury than in the intact LAD. However, the release of PA from the hearts after intimal injury was similar to findings in the intact hearts. We conclude from this study that thrombin plays an important role in regulating the coagulation-fibrinolysis system in endothelial cells and that changes in the properties of the endothelial cells may lead to initiation and enhancement of atherosclerosis.
 ...
PMID:Release of plasminogen activator from isolated perfused dog heart. 403 71

Prostacyclin (PGI(2)) is a potent vasodilator and inhibitor of platelet aggregation that is produced by prostacyclin synthase via the cyclooxygenase (COX) pathway of arachidonic acid metabolism. We investigated the potential role of COX-2 in the production of vasoactive prostanoids by aortic tissue in a rabbit model of dietary cholesterol-induced atherosclerosis. COX-1 was detected as the major isoform by immunoblot analysis in extracts from aortas of normal and 8 week cholesterol-fed animals with COX-2 being induced in atherosclerotic plaques from cholesterol-fed animals. Aortic tissue from cholesterol-fed animals showed decreased levels of basal 6-keto-PGF(1 alpha) and PGE(2) production as compared to the normal controls but showed no difference with respect to their ability to synthesize these prostanoids in response to exogenous arachidonic acid. The highly selective COX-2 inhibitors rofecoxib and the furanone DFP at concentrations of up to 10 micromol/l had no effect on the arachidonic acid-dependent production of 6-keto-PGF(1 alpha), in contrast to indomethacin, which caused a complete inhibition at 0.5 micromol/l. Celecoxib caused a significant inhibition of 6-keto-PGF(1 alpha) at 10 micromol/l but had little effect when the dose was lowered to 1 micromol/l. Similar effects of these inhibitors were observed with respect to the production of PGE(2) and no major difference was observed between aortic tissues from normal and cholesterol-fed animals with regard to inhibitor sensitivity. These results indicate that in a rabbit model of early stage cardiovascular disease, the basal production of 6-keto-PGF(1 alpha) and PGE(2) by aortic tissue is decreased. Furthermore, COX-2 expression is induced in atherosclerotic plaques and may play a role in altering localized synthesis of prostanoids in these lesions but does not appear to significantly impact the arachidonic acid-dependent prostacylin production of aortic tissues, which is largely mediated by COX-1.
Atherosclerosis 2001 Aug
PMID:Effects of COX-2 inhibitors on aortic prostacyclin production in cholesterol-fed rabbits. 1147 39