title: Myocardial Infarction Superimposed on Aging: MMP-9 Deletion Promotes M2 Macrophage Polarization.
abstract: In this study, we examined the combined effect of aging and myocardial infarction on left ventricular remodeling, focusing on matrix metalloproteinase (MMP)-9-dependent mechanisms. We enrolled 55 C57BL/6J wild type (WT) and 85 MMP-9 Null (Null) mice of both sexes at 11-36 months of age and evaluated their response at Day 7 post-myocardial infarction. Plasma MMP-9 levels positively linked to age in WT mice (r = .46, p = .001). MMP-9 deletion improved survival (76% for WT vs 88% for Null, p = .021). Post-myocardial infarction, there was a progressive increase in left ventricular dilation with age in WT but not in Null mice. By inflammatory gene array analysis, WT mice showed linear age-dependent increases in three different proinflammatory genes (C3, CCl4, and CX3CL1; all p < .05), whereas Null mice showed increases in three proinflammatory genes (CCL5, CCL9, and CXCL4; all p < .05) and seven anti-inflammatory genes (CCL1, CCL6, CCR1, IL11, IL1r2, IL8rb, and Mif; all p < .05). Compared with WT, macrophages isolated from Null left ventricle infarct demonstrated enhanced expression of anti-inflammatory M2 markers CD163, MRC1, TGF-β1, and YM1 (all p < .05), without affecting proinflammatory M1 markers. In conclusion, MMP-9 deletion stimulated anti-inflammatory polarization of macrophages to attenuate left ventricle dysfunction in the aging post-myocardial infarction.
authors: Department of Physiology and Biophysics, San Antonio Cardiovascular Proteomics Center, Mississippi Center for Heart Research, University of Mississippi Medical Center, Jackson.
authors: Andriy
authors: A
authors: Yabluchanskiy
authors: Department of Physiology and Biophysics, San Antonio Cardiovascular Proteomics Center, Mississippi Center for Heart Research, University of Mississippi Medical Center, Jackson.
authors: Yonggang
authors: Y
authors: Ma
authors: Department of Physiology and Biophysics, San Antonio Cardiovascular Proteomics Center, Mississippi Center for Heart Research, University of Mississippi Medical Center, Jackson.
authors: Kristine Y
authors: KY
authors: DeLeon-Pennell
authors: Department of Physiology and Biophysics, San Antonio Cardiovascular Proteomics Center, Mississippi Center for Heart Research, University of Mississippi Medical Center, Jackson.
authors: Raffaele
authors: R
authors: Altara
authors: Department of Physiology and Biophysics, San Antonio Cardiovascular Proteomics Center, Mississippi Center for Heart Research, University of Mississippi Medical Center, Jackson.
authors: Ganesh V
authors: GV
authors: Halade
authors: Department of Physiology and Biophysics, San Antonio Cardiovascular Proteomics Center, Mississippi Center for Heart Research, University of Mississippi Medical Center, Jackson. Department of Mechanical Engineering and.
authors: Andrew P
authors: AP
authors: Voorhees
authors: Department of Physiology and Biophysics, San Antonio Cardiovascular Proteomics Center, Mississippi Center for Heart Research, University of Mississippi Medical Center, Jackson. Department of Electrical and Computer Engineering, University of Texas at San Antonio.
authors: Nguyen T
authors: NT
authors: Nguyen
authors: Department of Physiology and Biophysics, San Antonio Cardiovascular Proteomics Center, Mississippi Center for Heart Research, University of Mississippi Medical Center, Jackson. Department of Electrical and Computer Engineering, University of Texas at San Antonio.
authors: Yu-Fang
authors: YF
authors: Jin
authors: Department of Physiology and Biophysics, San Antonio Cardiovascular Proteomics Center, Mississippi Center for Heart Research, University of Mississippi Medical Center, Jackson. Cardiology Division, University of Mississippi Medical Center, Jackson.
authors: Michael D
authors: MD
authors: Winniford
authors: Department of Physiology and Biophysics, San Antonio Cardiovascular Proteomics Center, Mississippi Center for Heart Research, University of Mississippi Medical Center, Jackson. Cardiology Division, University of Mississippi Medical Center, Jackson.
authors: Michael E
authors: ME
authors: Hall
authors: Department of Physiology and Biophysics, San Antonio Cardiovascular Proteomics Center, Mississippi Center for Heart Research, University of Mississippi Medical Center, Jackson. Department of Mechanical Engineering and.
authors: Hai-Chao
authors: HC
authors: Han
authors: Department of Physiology and Biophysics, San Antonio Cardiovascular Proteomics Center, Mississippi Center for Heart Research, University of Mississippi Medical Center, Jackson. Research Service, G.V. (Sonny) Montgomery Veterans Affairs Medical Center, Jackson, MS. mllindsey@umc.edu.
authors: Merry L
authors: ML
authors: Lindsey
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004452:Echocardiography; D005260:Female; D015870:Gene Expression; D007150:Immunohistochemistry; D008026:Ligation; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood* / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000201:enzymology* / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D016019:Survival Analysis; D020257:Ventricular Remodeling
chemical_list: D016207:Cytokines; D020780:Matrix Metalloproteinase 9
keywords: Aging; Cardiac remodeling; M2 phenotype.; Macrophage polarization