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)

Impairment in endothelial cell (EC) function plays a central role in vascular diseases (e.g. atherosclerosis, restenosis, diabetic angiopathies, microvascular angina, peripheral arterial disease). BRX-235 (a novel small molecule synthesized by Biorex, Hungary) has a potent vasculoprotective activity in different in vivo and in vitro studies. Since the importance of the p38 pathway in EC homeostasis and migration in particular is well documented, we have carried out studies to address the role of the p38 stress activated protein kinase (p38 SAPK) in the mode of action of BRX-235. In this study, Bovine aortic endothelial cells were used in a wounding migration assay (WMA) and for Western-blot analysis to study the effect and molecular mechanism of BRX-235-induced EC migration. The bovine aortic endothelial (BAE) cells were shown to be good models for EC migration. Both endothelial cell growth factor (ECGF)- and BRX-235-induced BAE cell migration were shown to be inhibited by SB 203580, a specific inhibitor of p38 SAPK. It was also shown that, BRX-235 induces phosphorylation of p38 SAPK without affecting p38 SAPK protein levels. Thus, BRX-235 acts upstream of p38 SAPK. In summary, we have shown that p38 SAPK is a potential pharmacological mediator for candidate drugs that target the endothelium.
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PMID:Pharmacologically activated migration of aortic endothelial cells is mediated through p38 SAPK. 1205 38

BRX-235 (Iroxanadine), a novel drug developed by Biorex (Hungary), was previously characterized as a vasculoprotector against atherosclerosis, an activator of p38 kinase, and an enhancer of stress-responsive heat shock protein (Hsp) expression. The present data demonstrate that BRX-235 may improve survival of vascular endothelial cells (ECs) following ischemia/reperfusion stress. ECs cultured from human umbilical veins were exposed to hypoxia/reoxygenation to mimic ischemia/reperfusion. Caspase activation and apoptosis were monitored in the reoxygenated cells. Addition of BRX-235 (0.1-1 microM) to culture medium prior to hypoxia or at start of reoxygenation significantly reduced the caspase-dependent apoptosis. The cytoprotection conferred by the pre-hypoxic drug administration was sensitive to quercetin and seems to be based on enhanced Hsp accumulation in stressed ECs. In the case of post-hypoxic drug administration, the cytoprotection was strongly inhibited by SB202190 and SB203580 and appears to be associated with enhanced p38 kinase activation in reoxygenated ECs.
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PMID:Pharmacological attenuation of apoptosis in reoxygenated endothelial cells. 1558 68