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Int J Med Sci 2013; 10(4):420-426. doi:10.7150/ijms.5723 This issue Cite

Research Paper

Inflammatory Stress Exacerbates the Progression of Cardiac Fibrosis in High-Fat-Fed Apolipoprotein E Knockout Mice via Endothelial-Mesenchymal Transition

Kun Ling Ma1, Jing Liu1, Jie Ni1, Yang Zhang1, Lin Li Lv1, Ri Ning Tang1, Hai Feng Ni1, Xiong Zhong Ruan2, Bi Cheng Liu1✉

1. Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing City, Jiangsu Province, China.
2. Centre for Nephrology, University College London (UCL) Medical School, Royal Free Campus, UK.

✉ Corresponding author: Bi Cheng Liu. Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, NO.87, Ding Jia Qiao Road, Nanjing City, Jiangsu Province, China, 210009. Tel: 0086 25 83285139 Fax 0086 25 83285130, E-mail: li More

Citation:
Ma KL, Liu J, Ni J, Zhang Y, Lv LL, Tang RN, Ni HF, Ruan XZ, Liu BC. Inflammatory Stress Exacerbates the Progression of Cardiac Fibrosis in High-Fat-Fed Apolipoprotein E Knockout Mice via Endothelial-Mesenchymal Transition. Int J Med Sci 2013; 10(4):420-426. doi:10.7150/ijms.5723. https://www.medsci.org/v10p0420.htm
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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.

Keywords: Dyslipidaemia, inflammation, EndMT, cardiac fibrosis

Citation styles

APA
Ma, K.L., Liu, J., Ni, J., Zhang, Y., Lv, L.L., Tang, R.N., Ni, H.F., Ruan, X.Z., Liu, B.C. (2013). Inflammatory Stress Exacerbates the Progression of Cardiac Fibrosis in High-Fat-Fed Apolipoprotein E Knockout Mice via Endothelial-Mesenchymal Transition. International Journal of Medical Sciences, 10(4), 420-426. https://doi.org/10.7150/ijms.5723.

ACS
Ma, K.L.; Liu, J.; Ni, J.; Zhang, Y.; Lv, L.L.; Tang, R.N.; Ni, H.F.; Ruan, X.Z.; Liu, B.C. Inflammatory Stress Exacerbates the Progression of Cardiac Fibrosis in High-Fat-Fed Apolipoprotein E Knockout Mice via Endothelial-Mesenchymal Transition. Int. J. Med. Sci. 2013, 10 (4), 420-426. DOI: 10.7150/ijms.5723.

NLM
Ma KL, Liu J, Ni J, Zhang Y, Lv LL, Tang RN, Ni HF, Ruan XZ, Liu BC. Inflammatory Stress Exacerbates the Progression of Cardiac Fibrosis in High-Fat-Fed Apolipoprotein E Knockout Mice via Endothelial-Mesenchymal Transition. Int J Med Sci 2013; 10(4):420-426. doi:10.7150/ijms.5723. https://www.medsci.org/v10p0420.htm

CSE
Ma KL, Liu J, Ni J, Zhang Y, Lv LL, Tang RN, Ni HF, Ruan XZ, Liu BC. 2013. Inflammatory Stress Exacerbates the Progression of Cardiac Fibrosis in High-Fat-Fed Apolipoprotein E Knockout Mice via Endothelial-Mesenchymal Transition. Int J Med Sci. 10(4):420-426.

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