title: Enhancement of matrix metalloproteinase 2 and 9 inhibitory action of minocycline by aspirin: an approach to attenuate outcome of acute myocardial infarction in diabetes.
abstract: OBJECTIVE
  Diabetes is a risk factor for exacerbated outcome after acute myocardial infarction (AMI) and doubles the risk of mortality after MI. Increased levels of MMP-2 and MMP-9 in diabetes cause vascular remodelling, which leads to cardiovascular complications of diabetes. We hypothesized that inhibition of MMP-2 and MMP-9 can reduce worsening of myocardial ischemia in diabetic patients. Further, we hypothesized that minocycline induced MMP-2 and MMP-9 inhibition will be potentiated by aspirin and the combination of both drugs will prevent worsening of MI in diabetic patients. In the present study, efficacy of combination of minocycline and aspirin to attenuate exacerbation of myocardial ischemia/reperfusion (I/R) injury in diabetic rats was evaluated.
  
  
  METHODS
  Diabetes was induced in male Wistar rats by streptozotocin (55 mg/kg i.p.). Three weeks after diabetes induction, rats were treated with minocycline (50 mg/kg, p.o.), aspirin (50 mg/kg, p.o.), or minocycline (50 mg/kg, p.o.) plus aspirin (50 mg/kg, p.o.) for a period of 3 weeks. At the end of week 6, I/R injury was induced by ligating the left anterior descending coronary artery for 30 min followed by 2 h reperfusion.
  
  
  RESULTS
  Percentage infarct volume, arrhythmias, mortality, collagen level and MMP-2 and MMP-9 level were significantly increased in vehicle-treated diabetic group when compared with normoglycemic rats. Treatment with a combination of minocycline and aspirin decreased percentage infarct volume, arrhythmias, mortality and collagen level when compared with vehicle-treated diabetic controls and showed reduced levels of MMP-2 and MMP-9.
  
  
  CONCLUSIONS
  Results of the present study suggest that the combination of minocycline and aspirin prevent worsening of AMI in diabetic rats.
authors.affiliation: Department of Pharmacology, Dr. Bhanuben Nanavati College of Pharmacy, Vile Parle (W), Mumbai, India. Electronic address: bhatt.lokesh@gmail.com.
authors.forename: Lokesh K
authors.initials: LK
authors.lastname: Bhatt
authors.affiliation: Department of Pharmacology, School of Pharmacy and Technology Management, NMIMS University, Vile Parle (W), Mumbai, India.
authors.forename: Addepalli
authors.initials: A
authors.lastname: Veeranjaneyulu
mesh_terms: D000818:Animals; D001241:Aspirin / Q000494:pharmacology / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000201:enzymology*; D004357:Drug Synergism; D006439:Hemodynamics; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D008911:Minocycline / Q000494:pharmacology / Q000627:therapeutic use*; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000201:enzymology / Q000209:etiology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000201:enzymology / Q000209:etiology; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; D013311:Streptozocin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D008911:Minocycline; D001241:Aspirin
keywords: Extracellular matrix; Matrix metalloproteinase 2; Matrix metalloproteinase 9; Myocardial ischemia/reperfusion