title: [Inflammation accelerates lipid dysregulation mediated cardiac fibrosis through enhancing myocardial endothelial-to-mesenchymal transition].
abstract: OBJECTIVE
  Dyslipidemia and chronic inflammation are risk factors of cardiac fibrosis. This study was aimed to investigate their possible synergetic effects and underlying mechanisms on progression of cardiac fibrosis in apolipoprotein E knockout (ApoE -/-) mice.
  
  
  METHODS
  Twenty-four ApoE-/- mice were divided into normal chow diet (control), high fat diet (HFD group), and HFD plus subcutaneously injection of 10% casein (inflammation group) for 8 weeks. Lipid profile and serum amyloid A (SAA) were examined by clinical biochemical assays and Enzyme-Linked Immunosorbent Assay, respectively. Hematoxylin-eosin staining (HE) and Masson staining were used to evaluate the myocardial accumulation of lipid and collagen. Collagen I protein expression was detected by immunohistochemical staining. Endothelial-to-mesenchymal transition related protein expressions were determined by Western blot.
  
  
  RESULTS
  Serum SAA level was significantly higher in inflammation group [(127.42 ± 26.99) ng/ml] than in control [(15.40 ± 7.62) ng/ml] and HFD [(8.17 ± 0.72) ng/ml] group (all P < 0.01).However serum levels of triglyceride, total cholesterol, and low density lipoprotein (LDL) cholesterol were significantly higher in HFD group than in inflammation and control groups[TG (7.53 ± 2.05) mmol/L vs. (3.43 ± 0.79) mmol/L; TC (27.80 ± 3.99) mmol/L vs. (14.94 ± 1.92) mmol/L;LDL-C (11.56 ± 2.56) mmol/L vs. (9.46 ± 1.31) mmol/L, all P < 0.05) . Foam cell formation in cardiac vessels, myocardial collagen deposit, protein expressions of collagen I, CD31, and alpha-smooth muscle actin (α-SMA) were all significantly higher in inflammation group than in HFD group (all P < 0.05) suggesting that inflammation contributes to the phenotype endothelial-to-mesenchymal transition in heart.
  
  
  CONCLUSIONS
  Inflammation exacerbates dyslipidemia mediated cardiac fibrosis in ApoE-/- mice partly through enhancing myocardial endothelial-to-mesenchymal transition.
authors.affiliation: Institute of Nephrology, Zhongda Hospital, Southeast University Medical School, Nanjing 210009, China. Email: mmkkll@hotmail.com.
authors.forename: Kun-ling
authors.initials: KL
authors.lastname: Ma
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Jie
authors.initials: J
authors.lastname: Ni
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Hai-feng
authors.initials: HF
authors.lastname: Ni
authors.forename: Lin-li
authors.initials: LL
authors.lastname: Lü
authors.forename: Bi-cheng
authors.initials: BC
authors.lastname: Liu
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D004195:Disease Models, Animal; D058750:Epithelial-Mesenchymal Transition; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000378:metabolism*; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D000685:Serum Amyloid A Protein / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D000685:Serum Amyloid A Protein