title: [The expression and molecular mechanism of M1 macrophages in rheumatic valvular disease].
abstract: OBJECTIVE
  To investigate whether valvular expression of macrophage and its subsets and correlative cytokines of mitral valve are altered in patients with rheumatic valvular disease.
  
  
  METHODS
  The mitral valvular leaflets of 15 rheumatic valvular disease patients were included as the test group, and 7 patients of terminal stage cardiomyopathy as the control. The immunostain of CD68, inducible nitric oxide synthase (iNOS) and CD163 were applied to mark the total macrophages, M1 and M2, respectively. The expression of endothelial nitric oxide synthase (eNOS), IL-10, Arg-1, macrophage-colony stimulating factor (M-CSF) were compared respectively in two groups.
  
  
  RESULTS
  The angiogenesis was enormous in the test, whereas the cell proliferation was scanty. Compared with the control, CD68 positive macrophages were markly expressed in the test (4.2 ± 2.0 vs. 3.2 ± 2.3; Z = -3.981, P = 0.000), also the iNOS positive M1 subsets (3.4 ± 1.7 vs. 1.2 ± 1.0; Z = -4.015, P = 0.000). The expression level of CD163 positive macrophages was lower in the test (1.2 ± 1.0 vs. 2.3 ± 1.8; Z = -8.602, P = 0.000). The expression of eNOS was higher in the rheumatic valve disease (4.9 ± 1.1 vs. 1.8 ± 1.1), but the expression levels of Arg-1 (1.0 ± 1.0 vs. 3.3 ± 1.3) and IL-10 (2.1 ± 1.2 vs. 4.9 ± 1.4) were lower (Z = -8.867 to -5.344, P = 0.000). The expression of M-CSF was lower in test (2.0 ± 1.4 vs. 4.3 ± 0.9; Z = -2.741, P = 0.006).
  
  
  CONCLUSIONS
  The infiltration of M1 macrophages plays an important role in the progression of rheumatic mitral valve disease. It fulfills the pro-inflammation by up-regulating the expression of eNOS. Inversely, it suppresses the expression of IL-10, Arg-1 to relieve the inflammatory action. In according with the down-regulated level of M-CSF, the polarization from M1 macrophages into M2 is depressed, and the inflammation induced by M1 is sustained.
authors.affiliation: Department of Thoracic & Cardiovascular Surgery, Nanjing First Hospital Affiliated to Nanjing Medical University, Nanjing 210006, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Deng
authors.forename: Wen
authors.initials: W
authors.lastname: Chen
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Wang
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006349:Heart Valve Diseases / Q000473:pathology*; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008943:Mitral Valve; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D012214:Rheumatic Heart Disease / Q000473:pathology*
chemical_list: C508609:IL10 protein, human; D016753:Interleukin-10; D016173:Macrophage Colony-Stimulating Factor; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III