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.

Design: Prospective randomized, animal study.

Setting: University research laboratory.

Subjects: Male Sprague-Dawley rats, 250-300 g.

Interventions: 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.

Measurements And Main 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.