Plasma monitoring of the myocardial specific tissue inhibitor of metalloproteinase-4 after alcohol septal ablation in hypertrophic obstructive cardiomyopathy.
BACKGROUND
The overall goal of this study was to develop an assay procedure for measuring the relative abundance of tissue inhibitor of metalloproteinase (TIMP)-4 in plasma, and then use this approach to determine dynamic changes of TIMP-4 levels in hypertrophic obstructive cardiomyopathic (HOCM) patients after an acute myocardial infarction (MI). Matrix metalloproteinases (MMPs) contribute to tissue remodeling and are regulated by the endogenous TIMPs. TIMP-4 is observed to be expressed in higher abundance in the myocardium when compared with other types of tissues. Recent clinical studies have measured changes in TIMP-4 levels; however, these studies have been limited to measuring this protein from myocardial tissue samples. To date, no studies have monitored TIMP-4 levels in plasma samples.


RESULTS
Plasma TIMP-4 levels were examined (by semiquantitative immunoblotting) in normal (n=18) and HOCM (n=16) patients after alcohol-induced MI. Serial measurements of plasma TIMP-4 levels were examined up to 60 hours after alcohol-induced MI in patients with HOCM. Unglycosylated plasma TIMP-4 levels increased 250% in the HOCM patients when compared with normal controls. Total plasma TIMP-4 levels decreased by 20% at 30 hours after alcohol-induced MI.


CONCLUSIONS
The unique results demonstrated that an induction of a controlled MI, specifically through alcohol ablation, caused a reduction in plasma TIMP-4 levels in HOCM patients after alcohol-induced MI that would facilitate myocardial remodeling in the early post-MI setting.
Stroud
Robert E
RE
Division of Cardiothoracic Surgery Medical University of South Carolina, Charleston, South Carolina 29403, USA.
Deschamps
Anne M
AM
Lowry
Abigail S
AS
Hardin
Amy E
AE
Mukherjee
Rupak
R
Lindsey
Merry L
ML
Ramamoorthy
Sammanda
S
Zile
Michael R
MR
Spencer
William H
WH
Spinale
Francis G
FG
D002312:Cardiomyopathy, Hypertrophic / Q000097:blood / Q000628:therapy*; D016022:Case-Control Studies; D017115:Catheter Ablation / Q000379:methods*; D004791:Enzyme Inhibitors / Q000097:blood; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D006346:Heart Septum; D006801:Humans; D015151:Immunoblotting; D008297:Male; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors; D008875:Middle Aged; D009203:Myocardial Infarction / Q000139:chemically induced; D009206:Myocardium / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases / Q000097:blood*; D020257:Ventricular Remodeling; D000097792:Tissue Inhibitor of Metalloproteinase-4
D004791:Enzyme Inhibitors; D000431:Ethanol; D008666:Metalloendopeptidases; D019714:Tissue Inhibitor of Metalloproteinases; D000097792:Tissue Inhibitor of Metalloproteinase-4