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Release of matrix metalloproteinases following alcohol septal ablation in hypertrophic obstructive cardiomyopathy.

Abstract：

OBJECTIVES:This study examined plasma levels of certain matrix metalloproteinase (MMP) and tissue inhibitor of matrix metalloproteinase (TIMP) species before and after alcohol-induced myocardial infarction (MI) in patients with hypertrophic obstructive cardiomyopathy (HOCM). BACKGROUND:Matrix metalloproteinases contribute to tissue remodeling, and endogenous control of MMP activity is achieved by the concordant release and binding of TIMPs. Animal models of MI have demonstrated a role for MMP activation in myocardial remodeling. However, the temporal relationship of MMP and TIMP release following a controlled myocardial injury in humans remains unknown. METHODS:Plasma levels for the gelatinases MMP-2 and MMP-9, and for the collagenases MMP-8 and MMP-13, as well as TIMP-1 profiles were examined (by enzyme-linked immunosorbent assay) at baseline and serially up to 60 h following alcohol injection into the septal perforator artery in order to induce an MI in 51 patients with HOCM (age 55 +/- 2 years). RESULTS:Plasma creatine kinase (MB isoform), indicating myocardial injury, increased 2,150% 18 h post-MI (p < 0.05). Plasma MMP-9 increased by over 400% and MMP-8 by over 100% from baseline values by 12 h post-MI (p < 0.05 vs. baseline). A similar temporal profile was not observed for MMP-2 and MMP-13. In addition, a concomitant increase in plasma TIMP-1 levels did not occur post-MI. As a result, MMP/TIMP stoichiometry (MMP-9/TIMP-1 ratio) increased significantly post-MI, suggestive of reduced TIMP-1 mediated MMP-9 inhibition, which would potentially enhance extracellular myocardial remodeling. CONCLUSIONS:These unique results demonstrated that induction of a controlled myocardial injury in humans, specifically through alcohol-induced MI, caused species- and time-dependent perturbations of MMP/TIMP stoichiometry that would facilitate myocardial remodeling in the early post-MI setting.

journal_name

J Am Coll Cardiol

journal_title

Journal of the American College of Cardiology

authors

Bradham WS,Gunasinghe H,Holder JR,Multani M,Killip D,Anderson M,Meyer D,Spencer WH 3rd,Torre-Amione G,Spinale FG

doi

10.1016/s0735-1097(02)02595-0

subject

Has Abstract

pub_date

2002-12-18 00:00:00

pages

2165-73

issue

eissn

0735-1097

issn

1558-3597

pii

S0735109702025950

journal_volume

pub_type

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Release of matrix metalloproteinases following alcohol septal ablation in hypertrophic obstructive cardiomyopathy.