title: Matrix metalloproteinase activities are altered in the heart and plasma during endotoxemia.
abstract: OBJECTIVE
  To investigate whether myocardial and plasma matrix metalloproteinase (MMP) activities are altered during endotoxemia.
  
  
  METHODS
  Prospective randomized, animal study.
  
  
  METHODS
  University research laboratory.
  
  
  METHODS
  Male Sprague-Dawley rats, 250-300 g.
  
  
  METHODS
  Rats were administered either bacterial lipopolysaccharide (LPS) or vehicle (pyrogen-free water). Groups of LPS-administered animals were killed at 0.5, 1, 3, 6, 12, and 24 hrs postinjection. Vehicle injected animals were killed at 6 hrs. Blood pressure was recorded before kill. Heart and plasma samples were analyzed by gelatin zymography and immunoblot.
  
  
  RESULTS
  Blood pressure was significantly depressed at 3-24 hrs post-LPS injection; however, overt symptoms of endotoxemia and reduction in blood pressure were most significant 6-12 hrs post-LPS. Heart samples from control rats revealed MMP-2 activity but no MMP-9 activity. MMP-2 activity was significantly depressed when overt symptoms of endotoxemia peaked at 6-12 hrs. Plasma MMP-2 activity significantly decreased 3-12 hrs after LPS injection. This loss of activity was associated with a loss of MMP-2 protein. In contrast, plasma MMP-9 activities were rapidly elevated following LPS injection, peaking between 1 and 12 hrs. MMP-9 activity correlated inversely with blood pressure.
  
  
  CONCLUSIONS
  Endotoxemia induced rapid changes in MMP activity in both the myocardium and plasma. An increase in circulating MMP-9 activity may contribute to endotoxemic cardiovascular dysfunction.
authors.affiliation: Department of Pharmacology, Cardiovascular Research Group, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Manoj M
authors.initials: MM
authors.lastname: Lalu
authors.forename: Tamás
authors.initials: T
authors.lastname: Csont
authors.forename: Richard
authors.initials: R
authors.lastname: Schulz
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D019446:Endotoxemia / Q000201:enzymology* / Q000503:physiopathology; D015151:Immunoblotting; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000097:blood / Q000378:metabolism*; D009206:Myocardium / Q000201:enzymology*; D011446:Prospective Studies; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000201:enzymology / Q000503:physiopathology
chemical_list: D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9