Specific temporal profile of matrix metalloproteinase release occurs in patients after myocardial infarction : Relation to left ventricular remodeling

• Published in: Circulation (New York, N.Y.) N.Y.), 2006-09, Vol.114 (10), p.1020-1027
• Main Authors: WEBB, Carson S, BONNEMA, David D, SPINALE, Francis G, AHMED, S. Hinan, LEONARDI, Amy H, MCCLURE, Catherine D, CLARK, Leslie L, STROUD, Robert E, CORN, William C, FINKLEA, Laura, ZILE, Michael R
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Biomarkers - blood; Blood and lymphatic vessels; Cardiology. Vascular system; Coronary heart disease; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Electrocardiography; Female; Gelatinases - blood; Heart; Humans; Male; Matrix Metalloproteinases - blood; Medical sciences; Middle Aged; Myocardial Infarction - blood; Myocardial Infarction - drug therapy; Myocardial Infarction - enzymology; Neurology; Reference Values; Thrombolytic Therapy; Tissue Inhibitor of Metalloproteinase-1 - blood; Tissue Inhibitor of Metalloproteinase-2 - blood; Vascular diseases and vascular malformations of the nervous system; Ventricular Remodeling - physiology
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/CIRCULATIONAHA.105.600353

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. 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). 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.