title: Targeted deletion of class A macrophage scavenger receptor increases the risk of cardiac rupture after experimental myocardial infarction.
abstract: BACKGROUND
  Class A macrophage scavenger receptor (SR-A) is a macrophage-restricted multifunctional molecule that optimizes the inflammatory response by modulation of the activity of inflammatory cytokines. This study was conducted with SR-A-deficient (SR-A(-/-)) mice to evaluate the relationship between SR-A and cardiac remodeling after myocardial infarction.
  
  
  RESULTS
  Experimental myocardial infarction (MI) was produced by ligation of the left coronary artery in SR-A(-/-) and wild-type (WT) male mice. The number of mice that died within 4 weeks after MI was significantly greater in SR-A(-/-) mice than in WT mice (P=0.03). Importantly, death caused by cardiac rupture within 1 week after MI was 31% (17 of 54 mice) in SR-A(-/-) mice and 12% (6 of 51 mice) in WT mice (P=0.01). In situ zymography demonstrated augmented gelatinolytic activity in the infarcted myocardium in SR-A(-/-) mice compared with WT mice. Real-time reverse transcription-polymerase chain reaction at day 3 after MI showed that the expression of matrix metalloproteinase-9 mRNA increased significantly in the infarcted myocardium in SR-A(-/-) mice compared with WT mice. Furthermore, SR-A(-/-) mice showed augmented expression of tumor necrosis factor-alpha and reduction of interleukin-10 in the infarcted myocardium at day 3 after MI. In vitro experiments also demonstrated increased tumor necrosis factor-alpha and decreased interleukin-10 expression in activated SR-A(-/-) macrophages.
  
  
  CONCLUSIONS
  The present findings suggest that SR-A deficiency might cause impairment of infarct remodeling that results in cardiac rupture via insufficient production of interleukin-10 and enhanced expression of tumor necrosis factor-alpha and of matrix metalloproteinase-9. SR-A might contribute to the prevention of cardiac rupture after MI.
authors: Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan.
authors: Kenichi
authors: K
authors: Tsujita
authors: Koichi
authors: K
authors: Kaikita
authors: Takanori
authors: T
authors: Hayasaki
authors: Tsuyoshi
authors: T
authors: Honda
authors: Hironori
authors: H
authors: Kobayashi
authors: Naomi
authors: N
authors: Sakashita
authors: Hiroshi
authors: H
authors: Suzuki
authors: Tatsuhiko
authors: T
authors: Kodama
authors: Hisao
authors: H
authors: Ogawa
authors: Motohiro
authors: M
authors: Takeya
mesh_terms: D000818:Animals; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D003433:Crosses, Genetic; D016207:Cytokines / Q000096:biosynthesis; D004790:Enzyme Induction; D017353:Gene Deletion; D006341:Heart Rupture / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control; D016753:Interleukin-10 / Q000032:analysis; D008077:Lipoproteins, LDL / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000150:complications* / Q000191:economics; D009206:Myocardium / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051117:Scavenger Receptors, Class A / Q000172:deficiency / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis / Q000235:genetics; D019714:Tissue Inhibitor of Metalloproteinases / Q000096:biosynthesis / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics; D020257:Ventricular Remodeling / Q000502:physiology*; D000097792:Tissue Inhibitor of Metalloproteinase-4
chemical_list: D016207:Cytokines; D016753:Interleukin-10; D008077:Lipoproteins, LDL; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D051117:Scavenger Receptors, Class A; D019715:Tissue Inhibitor of Metalloproteinase-1; D019714:Tissue Inhibitor of Metalloproteinases; D014409:Tumor Necrosis Factor-alpha; D000097792:Tissue Inhibitor of Metalloproteinase-4; C495140:Msr1 protein, mouse; C032629:acetyl-LDL