title: Matrix metalloproteinase-28 deletion exacerbates cardiac dysfunction and rupture after myocardial infarction in mice by inhibiting M2 macrophage activation.
abstract: BACKGROUND
  Matrix metalloproteinase (MMP)-28 regulates the inflammatory and extracellular matrix responses in cardiac aging, but the roles of MMP-28 after myocardial infarction (MI) have not been explored.
  
  
  OBJECTIVE
  To determine the impact of MMP-28 deletion on post-MI remodeling of the left ventricle (LV).
  
  
  RESULTS
  Adult C57BL/6J wild-type (n=76) and MMP null (MMP-28((-/-)), n=86) mice of both sexes were subjected to permanent coronary artery ligation to create MI. MMP-28 expression decreased post-MI, and its cell source shifted from myocytes to macrophages. MMP-28 deletion increased day 7 mortality because of increased cardiac rupture post-MI. MMP-28(-/-) mice exhibited larger LV volumes, worse LV dysfunction, a worse LV remodeling index, and increased lung edema. Plasma MMP-9 levels were unchanged in the MMP-28((-/-)) mice but increased in wild-type mice at day 7 post-MI. The mRNA levels of inflammatory and extracellular matrix proteins were attenuated in the infarct regions of MMP-28(-/-) mice, indicating reduced inflammatory and extracellular matrix responses. M2 macrophage activation was impaired when MMP-28 was absent. MMP-28 deletion also led to decreased collagen deposition and fewer myofibroblasts. Collagen cross-linking was impaired as a result of decreased expression and activation of lysyl oxidase in the infarcts of MMP-28(-/-) mice. The LV tensile strength at day 3 post-MI, however, was similar between the 2 genotypes.
  
  
  CONCLUSIONS
  MMP-28 deletion aggravated MI-induced LV dysfunction and rupture as a result of defective inflammatory response and scar formation by suppressing M2 macrophage activation.
authors.affiliation: San Antonio Cardiovascular Proteomics Center, San Antonio, TX, USA.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Ma
authors.forename: Ganesh V
authors.initials: GV
authors.lastname: Halade
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhang
authors.forename: Trevi A
authors.initials: TA
authors.lastname: Ramirez
authors.forename: Daniel
authors.initials: D
authors.lastname: Levin
authors.forename: Andrew
authors.initials: A
authors.lastname: Voorhees
authors.forename: Yu-Fang
authors.initials: YF
authors.lastname: Jin
authors.forename: Hai-Chao
authors.initials: HC
authors.lastname: Han
authors.forename: Anne M
authors.initials: AM
authors.lastname: Manicone
authors.forename: Merry L
authors.initials: ML
authors.lastname: Lindsey
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics; D002921:Cicatrix / Q000201:enzymology / Q000209:etiology; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D006341:Heart Rupture / Q000201:enzymology* / Q000209:etiology; D007249:Inflammation; D008262:Macrophage Activation / Q000502:physiology*; D008264:Macrophages / Q000145:classification / Q000201:enzymology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D053505:Matrix Metalloproteinases, Secreted / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000097:blood / Q000150:complications / Q000201:enzymology* / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000201:enzymology; D058628:Myofibroblasts / Q000378:metabolism; D008249:Protein-Lysine 6-Oxidase / Q000378:metabolism; D011654:Pulmonary Edema / Q000201:enzymology / Q000209:etiology; D018121:Receptors, Cytokine / Q000096:biosynthesis / Q000235:genetics; D014158:Transcription, Genetic; D018487:Ventricular Dysfunction, Left / Q000201:enzymology* / Q000209:etiology; D020257:Ventricular Remodeling / Q000235:genetics / Q000502:physiology
chemical_list: D015815:Cell Adhesion Molecules; D016207:Cytokines; D016326:Extracellular Matrix Proteins; D018121:Receptors, Cytokine; D003094:Collagen; D008249:Protein-Lysine 6-Oxidase; D053505:Matrix Metalloproteinases, Secreted; C477998:Mmp28 protein, mouse; D020780:Matrix Metalloproteinase 9