| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Unit of Cardiac Physiology, Division of Cardiovascular and Endocrine Sciences, University of Manchester, Manchester, United Kingdom
Submitted 3 April 2006 ; accepted in final form 24 October 2006
The cardiac extracellular matrix (ECM) maintains the structural and mechanical integrity of the myocardium. We determined the alterations in the composition of the ECM coincident with the transition from compensated left ventricular (LV) hypertrophy (LVH) to symptomatic congestive heart failure (CHF) and the mechanisms underlying such changes. Heart failure was induced in ferrets by aortic banding. Myocardial collagen content was assessed by HPLC and histological analysis. Matrix metalloproteinase (MMP) activity and tissue inhibitor of metalloproteinase (TIMP) expression were evaluated using gelatin zymography and Western blotting, respectively. LV free wall thickness increased by 29% in asymptomatic LVH and was associated with a 20% increase in interstitial fibrosis (P < 0.05). CHF was coincident with increased plasma angiotensin II levels (149 ± 48, 40 ± 19, and 5.6 ± 1 pg/ml for CHF, LVH, and sham, respectively; P < 0.01, CHF vs. sham and LVH), ventricular dilatation (LV internal diameter = 15 ± 0.4 vs. 9 ± 0.1 mm, P < 0.05), increased active MMP-9 (3.0- and 2.2-fold increase over sham and LVH, respectively, n = 5–10 animals per group, P < 0.01), and reduced myocardial total collagen content (3.5 ± 0.4, 2.6 ± 0.3, and 2.2 ± 0.3% in sham, LVH, and CHF, respectively, P < 0.05). In CHF the distribution of collagen was markedly altered, becoming punctate in nature. No difference in MMP-2 activity, TIMP-1, TIMP-2, TIMP-3, or TIMP-4 expression, or collagen cross-linking was found at any time. The present work demonstrates structural reorganization and loss of collagen from cardiac ECM during the transition to decompensated CHF. The enhanced MMP-9 activity coincident with the transition to CHF provides potential therapeutic opportunities for managing the progression from asymptomatic LVH to symptomatic CHF.
connective tissue; extracellular matrix; matrix metalloproteinase
This article has been cited by other articles:
|
|
 |
|
  G. E. Gonzalez, I. M. Seropian, M. L. Krieger, J. Palleiro, M. A. Lopez Verrilli, M. M. Gironacci, S. Cavallero, L. Wilensky, V. H. Tomasi, R. J. Gelpi, et al. Effect of early versus late AT1 receptor blockade with losartan on postmyocardial infarction ventricular remodeling in rabbits Am J Physiol Heart Circ Physiol, July 1, 2009; 297(1): H375 - H386. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Berni, M. Savi, L. Bocchi, F. Delucchi, E. Musso, C. Chaponnier, G. Gabbiani, S. Clement, and D. Stilli Modulation of actin isoform expression before the transition from experimental compensated pressure-overload cardiac hypertrophy to decompensation Am J Physiol Heart Circ Physiol, May 1, 2009; 296(5): H1625 - H1632. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. T. Weber, W. B. Weglicki, and R. U. Simpson Macro- and micronutrient dyshomeostasis in the adverse structural remodelling of myocardium Cardiovasc Res, February 15, 2009; 81(3): 500 - 508. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Pope, G. B. Sands, B. H. Smaill, and I. J. LeGrice Three-dimensional transmural organization of perimysial collagen in the heart Am J Physiol Heart Circ Physiol, September 1, 2008; 295(3): H1243 - H1252. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-H. Ning, E. Y. Chi, N. E. Buroker, S.-H. Chen, C.-S. Xu, Y.-T. Tien, O. M. Hyyti, M. Ge, and M. A. Portman Moderate hypothermia (30{degrees}C) maintains myocardial integrity and modifies response of cell survival proteins after reperfusion Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2119 - H2128. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
