Published Online
on August 21, 2006

A more recent version of this article appeared on September 5, 2006

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Submitted on December 13, 2004
Revised on June 13, 2006
Accepted on July 7, 2006

Specific Temporal Profile of Matrix Metalloproteinase Release Occurs in Patients After Myocardial Infarction. Relation to Left Ventricular Remodeling

Carson S. Webb MD, David D. Bonnema MD, S. Hinan Ahmed MD, Amy H. Leonardi BS, Catherine D. McClure RDCS, Leslie L. Clark MS, Robert E. Stroud MS, William C. Corn BA, Laura Finklea RN, Michael R. Zile MD, and Francis G. Spinale MD, PhD^*

From the Division of Cardiology, Department of Medicine (C.S.W., D.D.B., S.H.A., M.R.Z.), Department of Biostatistics, Bioinformatics and Epidemiology (L.L.C.), and Division of Cardiothoracic Surgery, Department of Surgery (A.H.L., C.D.M., L.L.C., R.E.S., W.C.C., L.F., F.G.S.), Medical University of South Carolina, and RHJ Department of Veterans Affairs Medical Center (M.R.Z., F.G.S.), Charleston, SC.

Background--Changes in matrix metalloproteinase (MMP) and tissue inhibitors of MMPs (TIMPs) contribute to left ventricular (LV) remodeling after myocardial infarction (MI). We tested the hypothesis that a specific plasma MMP/TIMP profile would emerge after MI and be associated with the degree of LV dilation.

Methods and Results--LV end-diastolic volume and MMP/TIMP plasma profiles were determined in 53 age-matched control subjects and 32 post-MI patients from day 1 through 180 after MI. LV end-diastolic volume increased by >38% at day 90 after MI (P<0.05). MMP-9 increased by >150% from control at day 1 after MI (P<0.05) and remained elevated. MMP-8 rose to >120% at day 3 after MI (P<0.05) and fell to control values by day 5. TIMP-1 increased by >60% from control at day 1 after MI (P<0.05), whereas TIMP-2 increased only at later time points. Cardiac-specific TIMP-4 fell by 40% at day 5 after MI and remained reduced. A persistent or elevated MMP-9 at day 5 was accompanied by a 3-fold end-diastolic volume increase at day 28 (P<0.05).

Conclusions--A specific temporal pattern of MMP/TIMPs occurred in post-MI patients that included an early and robust rise in MMP-9 and MMP-8 and a uniform fall in TIMP-4. These findings suggest that a specific MMP/TIMP plasma profile occurs after MI and holds both prognostic and diagnostic significance.

Key words: extracellular matrix • matrix metalloproteinases • myocardial infarction • remodeling

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