Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.35 (matrix metalloproteinase 9)
 2,207 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An increase in reactive oxygen species (ROS) through NADPH oxidase activation frequently follows stress that activates beta-adrenoreceptors, leading to deterioration of cardiovascular disease. We hypothesized that upregulation of NADPH oxidase in the vasculature causes mild vascular spasm subsequent to chronic isoproterenol (ISO) administration, correlating significantly with activation of both ETA and ETB receptors. We tested whether the dual endothelin receptor antagonist CPU0213 is effective in reversing ISO-induced vascular abnormality by suppressing activated NADPH oxidase in the vasculature. Rats were injected with ISO (1 mg/kg, SC) for 10 days to induce vascular dysfunction and treated with CPU0213 (30 mg/kg, SC) or aminoguanidine (AMG, an inhibitor of iNOS, 100 mg/kg, PO) from day 7 to day 10. On day 11, we found an increase in vascular response to phenylephrine (Phe) and reductions in NO availability and acetylcholine (ACh)-induced relaxation in ISO-treated rats along with upregulated mRNA of ETA, ETB, iNOS, NADPH oxidase-Phox22 and Phox47, and matrix metalloproteinase 9 (MMP9). These abnormalities were attenuated by 3 days of intervention with CPU0213 but less with AMG. CPU0213 was more effective in relieving enhanced vascular constriction and reversal of ET receptor and MMP9 expression in the vasculature than was AMG. In conclusion, an upregulation of NADPH oxidase phox 22 and phox 47, ETA and ETB, and MMP9 correlates with vascular abnormality and the endothelin receptor antagonist CPU0213 was more effective than AMG in reversing ISO-induced enhanced vascular constriction by normalizing the above abnormal expression.
 ...
PMID:The endothelin receptor antagonist CPU0213 is more effective than aminoguanidine to attenuate isoproterenol-induced vascular abnormality by suppressing overexpression of NADPH oxidase [correction of oxidas], ETA, ETB, and MMP9 in the vasculature. 1859 75

Endothelin (ET)-1 is a pro-fibrotic vasoconstrictive peptide causing microvascular dysfunction and cardiac remodelling after acute ST-elevation myocardial infarction (STEMI). It acts via two distinct receptors, ET-A and ET-B, and is involved in inflammation and atherogenesis. Patients with posterior-wall STEMI were randomly assigned to intravenous BQ-123 at 400 nmol/minute (min) or placebo over 60 min, starting immediately prior to primary percutaneous coronary intervention (n=54). Peripheral blood samples were drawn at baseline as well as after 24 hours and 30 days. Myeloperoxidase (MPO), as a marker of neutrophil activation and matrix metalloproteinase 9 (MMP-9), a marker of extracellular matrix degradation were measured in plasma. Clinical follow-up was conducted by an investigator blinded to treatment allocation over three years. During the median follow-up period of 3.6 years (interquartile range [IQR] 3.3-4.1) we observed a longer event-free survival in patients randomised to receive BQ-123 compared with patients randomised to placebo (mean 4.5 years (95% confidence interval: 3.9-5) versus mean 3 years (2.2-3.7), p=0.031). Patients randomised to ET-A receptor blockade demonstrated a greater reduction of MPO levels from baseline to 24 hours compared to placebo-treated patients (-177 ng/ml (IQR 103-274) vs -108 ng/ml (74-147), p=0.006). In addition, a pronounced drop in MMP-9 levels (-568 ng/ml (44-1157) vs -117 ng/ml (57-561), p=0.018) was observed. There was no significant difference in amino-terminal propetide of pro-collagen type III levels. In conclusion, short-term administration of BQ-123 leads to a reduction in MPO, as well as MMP-9 plasma levels and to a longer event-free survival in patients with STEMI.
...
PMID:Peri-interventional endothelin--a receptor blockade improves long-term outcome in patients with ST-elevation acute myocardial infarction. 2469 86