Matrix metalloproteinase activities are altered in the heart and plasma during endotoxemia.
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.
Lalu
Manoj M
MM
Department of Pharmacology, Cardiovascular Research Group, University of Alberta, Edmonton, Alberta, Canada.
Csont
Tamás
T
Schulz
Richard
R
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
D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9