Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151814 (coronary occlusion)
 3,687 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effects of bimoclomol, the novel heat shock protein (HSP) coinducer, was studied in various mammalian cardiac and rabbit aortic preparations. Bimoclomol decreased the ST-segment elevation induced by coronary occlusion in anesthetized dogs (56% and 80% reduction with 1 and 5 mg/kg, respectively). In isolated working rat hearts, bimoclomol increased coronary flow (CF), decreased the reduction of cardiac output (CO) and left ventricular developed pressure (LVDP) developing after coronary occlusion, and prevented ventricular fibrillation (VF) during reperfusion. In rabbit aortic preparations, precontracted with phenylephrine, bimoclomol induced relaxation (EC(50)=214 microM). Bimoclomol produced partial relaxation against 20 mM KCl, however, bimoclomol failed to relax preparations precontracted with serotonin, PGF(2) or angiotensin II. All these effects were evident within a few minutes after application of bimoclomol. A rapid bimoclomol-induced compartmental translocation of the already preformed HSPs may explain the protective action of the compound.
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PMID:In vivo and in vitro acute cardiovascular effects of bimoclomol. 1136 93

Although the cardioprotection of late preconditioning (PC) is known to be mediated by both inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2), the signaling mechanism responsible for COX-2 upregulation and the interaction between iNOS and COX-2 remain unknown. A total of 122 mice were used to address this issue. In wild-type mice preconditioned with six cycles of 4-min coronary occlusion-4-min reperfusion, ischemic PC resulted in rapid activation of nuclear STAT1/3 through tyrosine phosphorylation (STAT1: 339 +/- 48% of control; STAT3: 389 +/- 46% of control) and increased STAT1/3-DNA binding activity (687 +/- 58% of control) at 30 min after PC, with subsequent upregulation of COX-2 protein (373 +/- 60% of control) and activity(increased myocardial levels of PGE2, PGF(2alpha), and 6-keto-PGF(1alpha)) at 24 h. However, COX-1 protein was not changed 24 h after ischemic PC. Pretreatment with the Janus tyrosine kinase (JAK) inhibitor AG-490 before the six occlusion-reperfusion cycles blocked both the tyrosine phosphorylation of STAT1/3 and the subsequent upregulation of COX-2 protein, demonstrating a necessary role of the JAK-STAT pathway in the induction of COX-2. Targeted disruption of the iNOS gene (iNOS-/-) did not block the increased expression of COX-2 protein 24 h after ischemic PC but completely blocked the increase in COX-2 activity, whereas targeted disruption of the COX-2 gene (COX-2-/-) did not alter ischemic PC-induced iNOS induction. Immunoprecipitation of preconditioned heart tissues with anti-COX-2 antibodies followed by immunoblotting with anti-iNOS antibodies revealed that the increased iNOS protein co-precipitated with COX-2. We conclude that (i) the upregulation of COX-2 protein expression after ischemic PC is mediated by a JAK1/2-STAT1/3-signaling cascade; (ii) COX-2 activity requires upregulated iNOS and iNOS-derived NO; and (iii) COX-2 forms complexes with iNOS, supporting a direct interaction between these two proteins. To our knowledge, this is the first evidence that myocardial COX-2 is upregulated via a JAK1/2-STAT1/3 pathway.
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PMID:Mechanism of cyclooxygenase-2 upregulation in late preconditioning. 1273 34