Release of matrix metalloproteinases following alcohol septal ablation in hypertrophic obstructive cardiomyopathy.
OBJECTIVE
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.
Bradham
William S
WS
Medical University of South Carolina, Charleston 29425, USA.
Gunasinghe
Himali
H
Holder
Jennifer R
JR
Multani
Marlina
M
Killip
Donna
D
Anderson
Marianne
M
Meyer
Denise
D
Spencer
William H
WH
Torre-Amione
Guillermo
G
Spinale
Francis G
FG
D000438:Alcohols / Q000627:therapeutic use*; D019540:Area Under Curve; D002312:Cardiomyopathy, Hypertrophic / Q000097:blood* / Q000628:therapy; D005260:Female; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases / Q000097:blood*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000139:chemically induced*; D019714:Tissue Inhibitor of Metalloproteinases / Q000097:blood*
D000438:Alcohols; D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases