Acid fibroblast growth factor facilitates the progression of atherosclerotic plaques regardless of alterations in serum lipid expression levels in HFD‑fed ApoE‑/‑ mice

Han,Jibo; Du,Yao; Wang,Lintao; Chen,Xiong; Jiang,Liqin; Xu,Jianjiang

doi:10.3892/mmr.2018.9060

Acid fibroblast growth factor facilitates the progression of atherosclerotic plaques regardless of alterations in serum lipid expression levels in HFD‑fed ApoE‑/‑ mice

Authors:
- Jibo Han
- Yao Du
- Lintao Wang
- Xiong Chen
- Liqin Jiang
- Jianjiang Xu
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Affiliations: Department of Cardiology, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang 314000, P.R. China, Medication Department, Nanjing Drum Tower Hospital Affiliated to Medical College of Nanjing University, Nanjing, Jiangsu 210000, P.R. China, Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
Published online on: May 23, 2018 https://doi.org/10.3892/mmr.2018.9060
Pages: 1025-1030

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Abstract

Atherosclerosis is recognized at present as a chronic metabolic disease of the arteries that leads to multifocal plaque development. Previous studies have reported that acid fibroblast growth factor (aFGF) is a critical therapeutic regulator in numerous chronic metabolic disorders. However, there is currently no direct evidence indicating whether aFGF serves a therapeutic role in atherosclerosis. In the present study, the role of aFGF in atherosclerotic lesion development was investigated by examining high‑fat diet (HFD)‑fed apolipoprotein E (ApoE)‑/‑ mice and parenteral administration of aFGF. Increased expression of aFGF and peroxisome proliferator‑activated receptor α (PPARα) was observed during atherosclerotic lesion development. The parenteral delivery of aFGF facilitated the progression of atherosclerosis without altering serum lipid expression levels in HFD‑fed ApoE‑/‑ mice. Furthermore, it was demonstrated that aFGF increased the expression of PPARα and inflammatory cytokines. The present results provided evidence that aFGF accelerates the progression of atherosclerosis and suggested that aFGF may be a potential therapeutic target for the prevention of atherosclerosis development.

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1	Jonker JW, Suh JM, Atkins AR, Ahmadian M, Li P, Whyte J, He M, Juguilon H, Yin YQ, Phillips CT, et al: A PPARγ-FGF1 axis is required for adaptive adipose remodelling and metabolic homeostasis. Nature. 485:391–394. 2012. View Article : Google Scholar : PubMed/NCBI
2	Liu W, Struik D, Nies VJ, Jurdzinski A, Harkema L, de Bruin A, Verkade HJ, Downes M, Evans RM, van Zutphen T and Jonker JW: Effective treatment of steatosis and steatohepatitis by fibroblast growth factor 1 in mouse models of nonalcoholic fatty liver disease. Proc Natl Acad Sci USA. 113:2288–2293. 2016. View Article : Google Scholar : PubMed/NCBI
3	Pearson-Stuttard J, Guzman-Castillo M, Penalvo JL, Rehm CD, Afshin A, Danaei G, Kypridemos C, Gaziano T, Mozaffarian D, Capewell S and O'Flaherty M: Modeling future cardiovascular disease mortality in the United States: National trends and racial and ethnic disparities. Circulation. 133:967–978. 2016. View Article : Google Scholar : PubMed/NCBI
4	Daugherty A, Tall AR, Daemen MJAP, Falk E, Fisher EA, García-Cardeña G, Lusis AJ, Owens AP III, Rosenfeld ME, Virmani R, et al: Recommendation on design, execution, and reporting of animal atherosclerosis studies: A scientific statement from the American heart association. Arterioscler Thromb Vasc Biol. 37:e131–e157. 2017. View Article : Google Scholar : PubMed/NCBI
5	Brogi E, Winkles JA, Underwood R, Clinton SK, Alberts GF and Libby P: Distinct patterns of expression of fibroblast growth factors and their receptors in human atheroma and nonatherosclerotic arteries. Association of acidic FGF with plaque microvessels and macrophages. J Clin Invest. 92:2408–2418. 1993. View Article : Google Scholar : PubMed/NCBI
6	Liau G, Winkles JA, Cannon MS, Kuo L and Chilian WM: Dietary-induced atherosclerotic lesions have increased levels of acidic FGF mRNA and altered cytoskeletal and extracellular matrix mRNA expression. J Vasc Res. 30:327–332. 1993. View Article : Google Scholar : PubMed/NCBI
7	Tordjman K, Bernal-Mizrachi C, Zemany L, Weng S, Feng C, Zhang F, Leone TC, Coleman T, Kelly DP and Semenkovich CF: PPARalpha deficiency reduces insulin resistance and atherosclerosis in apoE-null mice. J Clin Invest. 107:1025–1034. 2001. View Article : Google Scholar : PubMed/NCBI
8	Wang L, Huang Z, Huang W, Chen X, Shan P, Zhong P, Khan Z, Wang J, Fang Q, Liang G and Wang Y: Inhibition of epidermal growth factor receptor attenuates atherosclerosis via decreasing inflammation and oxidative stress. Sci Rep. 8:459172017. View Article : Google Scholar : PubMed/NCBI
9	Lin Y, Bai L, Chen Y, Zhu N, Bai Y, Li Q, Zhao S, Fan J and Liu E: Practical assessment of the quantification of atherosclerotic lesions in apoE-/- mice. Mol Med Rep. 12:5298–5306. 2015. View Article : Google Scholar : PubMed/NCBI
10	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
11	Sorci-Thomas MG and Thomas MJ: Microdomains, inflammation, and atherosclerosis. Circ Res. 118:679–691. 2016. View Article : Google Scholar : PubMed/NCBI
12	Pawlak M, Lefebvre P and Staels B: Molecular mechanism of PPARα action and its impact on lipid metabolism, inflammation and fibrosis in non-alcoholic fatty liver disease. J Hepatol. 62:720–733. 2015. View Article : Google Scholar : PubMed/NCBI
13	Libby P, Ridker PM and Hansson GK: Progress and challenges in translating the biology of atherosclerosis. Nature. 473:317–325. 2011. View Article : Google Scholar : PubMed/NCBI
14	Raj T, Kanellakis P, Pomilio G, Jennings G, Bobik A and Agrotis A: Inhibition of fibroblast growth factor receptor signaling attenuates atherosclerosis in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol. 26:1845–1851. 2006. View Article : Google Scholar : PubMed/NCBI
15	Beenken A and Mohammadi M: The FGF family: Biology, pathophysiology and therapy. Nat Rev Drug Discov. 8:235–253. 2009. View Article : Google Scholar : PubMed/NCBI
16	Cordon-Cardo C, Vlodavsky I, Haimovitz-Friedman A, Hicklin D and Fuks Z: Expression of basic fibroblast growth factor in normal human tissues. Lab Invest. 63:832–840. 1990.PubMed/NCBI
17	Sigala F, Savvari P, Liontos M, Sigalas P, Pateras IS, Papalampros A, Basdra EK, Kolettas E, Papavassiliou AG and Gorgoulis VG: Increased expression of bFGF is associated with carotid atherosclerotic plaques instability engaging the NF-κB pathway. J Cell Mol Med. 14:2273–2280. 2010. View Article : Google Scholar : PubMed/NCBI
18	Lin Z, Pan X, Wu F, Ye D, Zhang Y, Wang Y, Jin L, Lian Q, Huang Y, Ding H, et al: Fibroblast growth factor 21 prevents atherosclerosis by suppression of hepatic sterol regulatory element-binding protein-2 and induction of adiponectin in mice. Circulation. 131:1861–1871. 2015. View Article : Google Scholar : PubMed/NCBI