Advertisement






Click here for more guidelines.
CME Topic Collections Past Issues Search Current Issue Home
     

J Am Coll Cardiol, 2002; 40:2165-2173
© 2002 by the American College of Cardiology Foundation
This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bradham, W. S.
Right arrow Articles by Spinale, F. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bradham, W. S., Jr
Right arrow Articles by Spinale, F. G.

CLINICAL STUDY

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

William S. Bradham, Jr, PhD*, Himali Gunasinghe, BS*, Jennifer R. Holder, BS*, Marlina Multani, MS*, Donna Killip, RN*, Marianne Anderson, RN{dagger}, Denise Meyer, RN{dagger}, William H. Spencer, III, MD, FACC*, Guillermo Torre-Amione, MD, FACC{dagger} and Francis G. Spinale, MD, PhD, FACC*,*

* Medical University of South Carolina, Charleston, South Carolina, USA
{dagger} Baylor College of Medicine, Houston, Texas, USA

Manuscript received May 10, 2002; revised manuscript received July 22, 2002, accepted September 6, 2002.

* Reprint requests and correspondence: Dr. Francis G. Spinale, Cardiothoracic Surgery, Room 625, Strom Thurmond Research Building, 770 MUSC Complex, Medical University of South Carolina, 114 Doughty Street, Charleston, South Carolina 29425, USA.
wilburnm{at}musc.edu

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.

Abbreviations and Acronyms
  ANOVA
  analysis of variance
  CHF
  congestive heart failure
  CK
  creatine kinase
  HOCM
  hypertrophic obstructive cardiomyopathy
  LV
  left ventricle/ventricular
  LVOT
  left ventricular outflow tract
  MI
  myocardial infarction
  MMP
  matrix metalloproteinases
  TIMP
  tissue inhibitor of matrix metalloproteinases




This article has been cited by other articles:


Home page
Physiol. Rev.Home page
F. G. Spinale
Myocardial Matrix Remodeling and the Matrix Metalloproteinases: Influence on Cardiac Form and Function
Physiol Rev, October 1, 2007; 87(4): 1285 - 1342.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
C. S. Webb, D. D. Bonnema, S. H. Ahmed, A. H. Leonardi, C. D. McClure, L. L. Clark, R. E. Stroud, W. C. Corn, L. Finklea, M. R. Zile, et al.
Specific Temporal Profile of Matrix Metalloproteinase Release Occurs in Patients After Myocardial Infarction: Relation to Left Ventricular Remodeling
Circulation, September 5, 2006; 114(10): 1020 - 1027.
[Abstract] [Full Text] [PDF]


Home page
J. Pharmacol. Exp. Ther.Home page
F. G. Spinale, G. P. Escobar, J. W. Hendrick, L. L. Clark, S. S. Camens, J. P. Mingoia, C. G. Squires, R. E. Stroud, and J. S. Ikonomidis
Chronic Matrix Metalloproteinase Inhibition Following Myocardial Infarction in Mice: Differential Effects on Short and Long-Term Survival
J. Pharmacol. Exp. Ther., September 1, 2006; 318(3): 966 - 973.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
R. E. Chapman and F. G. Spinale
Extracellular protease activation and unraveling of the myocardial interstitium: critical steps toward clinical applications
Am J Physiol Heart Circ Physiol, January 1, 2004; 286(1): H1 - H10.
[Full Text] [PDF]



 
  CME Topic Collections Past Issues Search Current Issue Home

Advertisement