Inflammation accelerates lipid dysregulation mediated cardiac fibrosis through enhancing myocardial endothelial-to-mesenchymal transition
10.3760/cma.j.issn.0253-3758.2013.07.019
- VernacularTitle:微炎症致脂质稳态失调在小鼠心肌纤维化中的作用
- Author:
Kun-Ling MA
1
;
Jing LIU
;
Jie NI
;
Yang ZHANG
;
Hai-Feng NI
;
Lin-Li L(U)
;
Bi-Cheng LIU
Author Information
1. 东南大学附属中大医院肾内科肾脏病研究所
- Keywords:
Hyperlipidema;
Inflammation;
Myocardium;
Fibrosis
- From:
Chinese Journal of Cardiology
2013;41(7):602-606
- CountryChina
- Language:Chinese
-
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.Conclusion Inflammation exacerbates dyslipidemia mediated cardiac fibrosis in ApoE-/-mice partly through enhancing myocardial endothelial-to-mesenchymal transition.
