title: Inflammatory stress exacerbates the progression of cardiac fibrosis in high-fat-fed apolipoprotein E knockout mice via endothelial-mesenchymal transition.
abstract: Background Chronic inflammation plays a crucial role in the progression of cardiac fibrosis. This study investigated whether inflammation exacerbated the progression of cardiac fibrosis in high-fat-fed apolipoprotein E knockout (ApoE KO) mice via endothelial-mesenchymal transition (EndMT). Methods Twenty-four male ApoE KO mice were divided into normal chow diet (Control), high-fat diet (HFD), or high-fat diet plus 10% casein injection (inflamed) groups for 8 weeks. The body weight of ApoE KO mice was measured at each week. The lipid profile and serum amyloid A (SAA) levels were examined using clinical biochemistry and enzyme-linked immunosorbent assays, respectively. Cardiac lipid and collagen accumulation was visualised with haematoxylin-eosin (HE) and Masson's trichrome staining. EndMT-related molecule expression was examined by immunohistochemistry and Western blotting. Results SAA levels were increased in the inflamed group compared with the HFD and control groups, suggesting that inflammation was successfully induced. There were no differences in body weight among three groups at each week. Interestingly, inflammation significantly reduced serum total cholesterol, triglyceride, and low-density lipoprotein (LDL) levels compared with the HFD mice. However, both foam cell formation in cardiac blood vessels and cardiac collagen deposition were increased in the inflamed group, as demonstrated by HE and Masson trichrome staining. Furthermore, inflammation reduced protein expression of CD31 and increased protein expression of alpha-smooth muscle actin (α-SMA) and collagen I, which contribute to cardiac EndMT. Conclusions Inflammatory stress exacerbates the progression of cardiac fibrosis in high-fat-fed ApoE KO mice via EndMT, suggesting that hyperlipidaemia and inflammation act synergistically to redistribute plasma lipids to cardiac tissues and accelerate the progression of cardiac fibrosis.
authors.affiliation: Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing City, Jiangsu Province, China.
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: Lin Li
authors.initials: LL
authors.lastname: Lv
authors.forename: Ri Ning
authors.initials: RN
authors.lastname: Tang
authors.forename: Hai Feng
authors.initials: HF
authors.lastname: Ni
authors.forename: Xiong Zhong
authors.initials: XZ
authors.lastname: Ruan
authors.forename: Bi Cheng
authors.initials: BC
authors.lastname: Liu
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics* / Q000378:metabolism; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology; D059305:Diet, High-Fat; D004727:Endothelium / Q000166:cytology / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005355:Fibrosis / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D008055:Lipids / Q000097:blood*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D000685:Serum Amyloid A Protein / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
chemical_list: D000199:Actins; D001057:Apolipoproteins E; D008055:Lipids; D000685:Serum Amyloid A Protein; D014280:Triglycerides; C544013:alpha-smooth muscle actin, mouse
keywords: Dyslipidaemia; EndMT; cardiac fibrosis; inflammation