Abstract | OBJECTIVES:
Ventricular remodeling after myocardial infarction begins with massive extracellular matrix deposition and resultant fibrosis. This loss of functional tissue and stiffening of myocardial elastic and contractile elements starts the vicious cycle of mechanical inefficiency, adverse remodeling, and eventual heart failure. We hypothesized that stromal cell-derived factor 1α (SDF-1α) therapy to microrevascularize ischemic myocardium would rescue salvageable peri- infarct tissue and subsequently improve myocardial elasticity. METHODS: Immediately after left anterior descending coronary artery ligation, mice were randomly assigned to receive peri- infarct injection of either saline solution or SDF-1α. After 6 weeks, animals were killed and samples were taken from the peri- infarct border zone and the infarct scar, as well as from the left ventricle of noninfarcted control mice. Determination of tissues' elastic moduli was carried out by mechanical testing in an atomic force microscope. RESULTS: SDF-1α-treated peri- infarct tissue most closely approximated the elasticity of normal ventricle and was significantly more elastic than saline-treated peri- infarct myocardium (109 ± 22.9 kPa vs 295 ± 42.3 kPa; P < .0001). Myocardial scar, the strength of which depends on matrix deposition from vasculature at the peri- infarct edge, was stiffer in SDF-1α-treated animals than in controls (804 ± 102.2 kPa vs 144 ± 27.5 kPa; P < .0001). CONCLUSIONS: Direct quantification of myocardial elastic properties demonstrates the ability of SDF-1α to re-engineer evolving myocardial infarct and peri- infarct tissues. By increasing elasticity of the ischemic and dysfunctional peri- infarct border zone and bolstering the weak, aneurysm-prone scar, SDF-1α therapy may confer a mechanical advantage to resist adverse remodeling after infarction.
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Authors | William Hiesinger, Matthew J Brukman, Ryan C McCormick, J Raymond Fitzpatrick 3rd, John R Frederick, Elaine C Yang, Jeffrey R Muenzer, Nicole A Marotta, Mark F Berry, Pavan Atluri, Y Joseph Woo |
Journal | The Journal of thoracic and cardiovascular surgery
(J Thorac Cardiovasc Surg)
Vol. 143
Issue 4
Pg. 962-6
(Apr 2012)
ISSN: 1097-685X [Electronic] United States |
PMID | 22264415
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
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Copyright | Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved. |
Chemical References |
- Angiogenesis Inducing Agents
- Chemokine CXCL12
|
Topics |
- Angiogenesis Inducing Agents
(pharmacology)
- Animals
- Biomechanical Phenomena
- Chemokine CXCL12
(pharmacology)
- Disease Models, Animal
- Elastic Modulus
- Elasticity Imaging Techniques
(methods)
- Fibrosis
- Heart Ventricles
(drug effects, pathology, physiopathology)
- Male
- Mice
- Microscopy, Atomic Force
- Myocardial Infarction
(drug therapy, pathology, physiopathology)
- Myocardium
(pathology)
- Neovascularization, Physiologic
(drug effects)
- Time Factors
- Ventricular Remodeling
(drug effects)
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