Inflammatory stress exacerbates the progression of cardiac fibrosis in high-fat-fed apolipoprotein E knockout mice via endothelial-mesenchymal transition - PubMed (original) (raw)

Inflammatory stress exacerbates the progression of cardiac fibrosis in high-fat-fed apolipoprotein E knockout mice via endothelial-mesenchymal transition

Kun Ling Ma et al. Int J Med Sci. 2013.

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; EndMT; cardiac fibrosis; inflammation.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Fig 1

Serum SAA levels at experimental termination (n=8). ApoE KO mice were fed normal chow (Control) or Western diet for eight weeks without (HFD group) or with 10% casein injections (Inflamed group). Abbreviations: SAA, serum amyloid A. *p<0.001 vs. Control.

Fig 2

Body weight change at each week (n=8). ApoE KO mice were fed normal chow (Control) or Western diet for eight weeks without (HFD group) or with 10% casein injections (Inflamed group). The body weight change was measured at each week.

Fig 3

Serum lipid profile analysis at experimental termination (n=8). ApoE KO mice were fed normal chow (Control) or Western diet for eight weeks without (HFD group) or with 10% casein injections (Inflamed group). Abbreviations: TC, total cholesterol; TG, triglyceride; LDL, low-density lipoprotein; HDL, high-density lipoprotein; *p<0.05 vs. Control, **p<0.001 vs. Control, ***p<0.001 vs. HFD group.

Fig 4

Effect of inflammation on lipid deposition in cardiac blood vessels and cardiac collagen deposition in high-fat-fed ApoE KO mice (n=8). ApoE KO mice were fed normal chow (Control) or Western diet for eight weeks without (HFD group) or with 10% casein injections (Inflamed group). Cardiac blood vessel lipid deposition was assessed by HE staining (A, original magnification×400), and cardiac collagen deposition was assessed by Masson's trichrome (B, blue colour, original magnification×100) and the values of semiquantitative analysis for the positive areas are expressed as the Mean ±SD from six ApoE KO mice at each group. *p < 0.001 vs. control, **p<0.01 vs. HFD group (C). The collagen I protein expression was measured by immunohistochemical staining (D, brown colour, original magnification×100).

Fig 4

Fig 5

Inflammation accelerated hyperlipidaemia-mediated cardiac fibrosis by contributing to EndMT (n=8). ApoE KO mice were fed normal chow (Control) or Western diet for eight weeks without (HFD group) or with 10% casein injections (Inflamed group). Collagen I, CD31, and α-SMA protein expression was assessed by Western blot (A and B). The histogram represented Mean ± SD of the densitometric scans of the protein bands from eight ApoE KO mice per group, normalized by comparison with β-actin .*p<0.01 vs. control, **p<0.001 vs. control, ***p<0.001 vs. HFD group.

Fig 5

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Inflammatory stress exacerbates the progression of cardiac fibrosis in high-fat-fed apolipoprotein E knockout mice via endothelial-mesenchymal transition - PubMed (original) (raw)