Sevoflurane promotes the proliferation of HUVECs by activating VEGF signaling

Wang,Zengtao; Wu,Cui; Zhang,Min; Dong,Aiping; Niu,Ruibin; Zhang,Jie

doi:10.3892/etm.2019.8319

Sevoflurane promotes the proliferation of HUVECs by activating VEGF signaling

Authors:
- Zengtao Wang
- Cui Wu
- Min Zhang
- Aiping Dong
- Ruibin Niu
- Jie Zhang
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Affiliations: Department of Anesthesiology, Huashan Hospital‑North Fudan University, Shanghai 201907, P.R. China, Department of Anesthesiology, Central Hospital of Shanghai Yangpu District Affiliated to Tongji University, Shanghai 201907, P.R. China
Published online on: December 12, 2019 https://doi.org/10.3892/etm.2019.8319
Pages: 1336-1342
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The vascular endothelium plays an essential role in vascular disease and cardiovascular diseases. The effects and underlying mechanisms of sevoflurane on vascular endothelial growth factor (VEGF) in human endothelial cells have not been elucidated. The MTT colorimetric assay was used to determine HUVEC activity at different concentrations (1 and 3%, respectively) of sevoflurane for different time‑points (12, 24 and 48 h, respectively). The regulation of sevoflurane on the mRNA levels of VEGFa, VEGFb, VEGFc and VEGFR1, 2, 3 was analyzed by real‑time PCR. When VEGFR2 was inhibited by axitinib, VEGFR2 protein expression was determined by western blotting, and the cell viability was assessed by MTT analysis. The results revealed that sevoflurane increased cell viability in a dose‑ and time‑dependent manner. Sevoflurane significantly upregulated VEGFA mRNA expression only. In addition, sevoflurane increased the expression of VEGFR2 at the mRNA and protein levels, whereas sevoflurane did not modulate the mRNA expression of VEGFR1 and VEGFR3. Furthermore, sevoflurane failed to increase the mRNA and protein expression of VEGFR2 when VEGFR2 was inhibited by axitinib, an inhibitor of VEGF receptors. In conclusion, sevoflurane may be a promising agent against endothelium dysfunction‑caused vascular disease by activating the VEGF‑A/VEGFR2 signaling pathway.

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1	Davignon J and Ganz P: Role of endothelial dysfunction in atherosclerosis. Circulation. 109:27–32. 2004. View Article : Google Scholar
2	Yoder MC: Human endothelial progenitor cells. Cold Spring Harbor Perspect Med. 2:a0066922012. View Article : Google Scholar
3	Chhabra N: Endothelial dysfunction-A predictor of atherosclerosis. Inter J Med Update. 4:33–41. 2009.
4	Park KH and Park WJ: Endothelial dysfunction: Clinical implications in cardiovascular disease and therapeutic approaches. J Korean Med Sci. 30:1213–1225. 2015. View Article : Google Scholar : PubMed/NCBI
5	Rajendran P, Rengarajan T, Thangavel J, Nishigaki Y, Sakthisekaran D, Sethi G and Nishigaki I: The vascular endothelium and human diseases. Int J Biol Sci. 9:1057–1069. 2013. View Article : Google Scholar : PubMed/NCBI
6	Werner N, Junk S, Laufs U, Link A, Walenta K, Bohm M and Nickenig G: Intravenous transfusion of endothelial progenitor cells reduces neointima formation after vascular injury. Circ Res. 93:e17–e24. 2003. View Article : Google Scholar : PubMed/NCBI
7	Huang PH, Chen YH, Chen YL, Wu TC, Chen JW and Lin SJ: Vascular endothelial function and circulating endothelial progenitor cells in patients with cardiac syndrome X. Heart. 93:1064–1070. 2007. View Article : Google Scholar : PubMed/NCBI
8	Lin JM, Zhao JY, Zhuang QC, Hong ZF and Peng J: Xiongshao capsule promotes angiogenesis of HUVEC via enhancing cell proliferation and up-regulating the expression of bFGF and VEGF. Chin J Integr Med. 17:840–846. 2011. View Article : Google Scholar : PubMed/NCBI
9	Carratelli CR, Paolillo R and Rizzo A: Chlamydia pneumoniae stimulates the proliferation of HUVEC through the induction of VEGF by THP-1. Int Immunopharmacol. 7:287–294. 2007. View Article : Google Scholar : PubMed/NCBI
10	Hassel D, Cheng P, White MP, Ivey KN, Kroll J, Augustin HG, Katus HA, Stainier DY and Srivastava D: MicroRNA-10 regulates the angiogenic behavior of zebrafish and human endothelial cells by promoting vascular endothelial growth factor signaling. Circ Res. 111:1421–1433. 2012. View Article : Google Scholar : PubMed/NCBI
11	Liu X, Song X, Yuan T, He J, Wang X and Wang Q: Effects of calpain on sevoflurane-induced aged rats hippocampal neuronal apoptosis. Aging Clin Exp Res. 28:633–639. 2016. View Article : Google Scholar : PubMed/NCBI
12	Hofstetter C, Boost KA, Flondor M, Basagan-Mogol E, Betz C, Homann M, Muhl H, Pfeilschifter J and Zwissler B: Anti-inflammatory effects of sevoflurane and mild hypothermia in endotoxemic rats. Acta Anaesthesiol Scand. 51:893–899. 2007. View Article : Google Scholar : PubMed/NCBI
13	Herrmann IK, Castellon M, Schwartz DE, Hasler M, Urner M, Hu G, Minshall RD and Beck-Schimmer B: Volatile anesthetics improve survival after cecal ligation and puncture. Anesthesiology. 119:901–906. 2013. View Article : Google Scholar : PubMed/NCBI
14	Julier K, da Silva R, Garcia C, Bestmann L, Frascarolo P, Zollinger A, Chassot PG, Schmid ER, Turina MI, von Segesser LK, et al: Preconditioning by sevoflurane decreases biochemical markers for myocardial and renal dysfunction in coronary artery bypass graft surgery: A double-blinded, placebo-controlled, multicenter study. Anesthesiology. 98:1315–1327. 2003. View Article : Google Scholar : PubMed/NCBI
15	Sun SX, Ge BX and Miao CH: Effects of preconditioning with sevoflurane on TNF-α-induced permeability and activation of p38 MAPK in rat pulmonary microvascular endothelial cells. Cell Biochem Biophys. 61:123–129. 2011. View Article : Google Scholar : PubMed/NCBI
16	Ebert TJ, Harkin CP and Muzi M: Cardiovascular responses to sevoflurane: A review. Anesth Analg. 81 (Suppl 6):S11–S22. 1995. View Article : Google Scholar : PubMed/NCBI
17	Vlad AM, Isvoranu G, Gilca M, Ceafalan L, Surcel M, Stoian I and Manda G: Sevoflurane increases proliferation, adhesion on HUVEC and incorporation in tubular structures of endothelial progenitor cells. FASEB J. 29:LB5902015.
18	Yang Y, Hu R, Yan J, Chen Z, Lu Y, Jiang J and Jiang H: Sevoflurane inhibits the malignant potential of head and neck squamous cell carcinoma via activating the hypoxiainducible factor-1α signaling pathway in vitro. Int J Mol Med. 41:995–1002. 2018.PubMed/NCBI
19	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
20	Saffi MA, Furtado MV, Polanczyk CA, Montenegro MM, Ribeiro IW, Kampits C, Haas AN, Rösing CK and Rabelo-Silva ER: Relationship between vascular endothelium and periodontal disease in atherosclerotic lesions: Review article. World J Cardiol. 7:26–30. 2015. View Article : Google Scholar : PubMed/NCBI
21	Meguro K, Iidaka T, Nakata M, Yamashita T, Chinen T, Fujita M, Kikuchi T, Keida T and Ohira H: Regular exercise habits and vascular endothelium function in patients with cardiovascular diseases. Eur Heart J. 35:730–731. 2014.
22	Gerber HP, Vu TH, Ryan AM, Kowalski J, Werb Z and Ferrara N: VEGF couples hypertrophic cartilage remodeling, ossification and angiogenesis during endochondral bone formation. Nat Med. 5:623–628. 1999. View Article : Google Scholar : PubMed/NCBI
23	Dzietko M, Derugin N, Wendland MF, Vexler ZS and Ferriero DM: Delayed VEGF treatment enhances angiogenesis and recovery after neonatal focal rodent stroke. Transl Stroke Res. 4:189–200. 2013. View Article : Google Scholar : PubMed/NCBI
24	Lopes RA, Neves KB, Tostes RC, Montezano AC and Touyz RM: Downregulation of nuclear factor Erythroid 2-related factor and associated antioxidant genes contributes to redox-sensitive vascular dysfunction in hypertension. Hypertension. 66:1240–1250. 2015. View Article : Google Scholar : PubMed/NCBI
25	Neves KB, Rios FJ, van der Mey L, Alves-Lopes R, Cameron AC, Volpe M, Montezano AC, Savoia C and Touyz RM: VEGFR (Vascular Endothelial Growth Factor Receptor) inhibition induces cardiovascular damage via redox-sensitive processes. Hypertension. 71:638–647. 2018. View Article : Google Scholar : PubMed/NCBI
26	Ferrara N, Carver-Moore K, Chen H, Dowd M, Lu L, O'Shea KS, Powell-Braxton L, Hillan KJ and Moore MW: Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature. 380:439–442. 1996. View Article : Google Scholar : PubMed/NCBI
27	Carmeliet P, Ferreira V, Breier G, Pollefeyt S, Kieckens L, Gertsenstein M, Fahrig M, Vandenhoeck A, Harpal K, Eberhardt C, et al: Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature. 380:435–439. 1996. View Article : Google Scholar : PubMed/NCBI
28	Takahashi H and Shibuya M: The vascular endothelial growth factor (VEGF)/VEGF receptor system and its role under physiological and pathological conditions. Clin Sci (Lond). 109:227–241. 2005. View Article : Google Scholar : PubMed/NCBI
29	Fong GH, Rossant J, Gertsenstein M and Breitman ML: Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium. Nature. 376:66–70. 1995. View Article : Google Scholar : PubMed/NCBI
30	Roberts DM, Kearney JB, Johnson JH, Rosenberg MP, Kumar R and Bautch VL: The vascular endothelial growth factor (VEGF) receptor Flt-1 (VEGFR-1) modulates Flk-1 (VEGFR-2) signaling during blood vessel formation. Am J Pathol. 164:1531–1535. 2004. View Article : Google Scholar : PubMed/NCBI
31	Jiang JX, Chen XL, Serizawa N, Szyndralewiez C, Page P, Schröder K, Brandes RP, Devaraj S and Török NJ: Liver fibrosis and hepatocyte apoptosis are attenuated by GKT137831, a novel NOX4/NOX1 inhibitor in vivo. Free Radic Biol Med. 53:289–296. 2012. View Article : Google Scholar : PubMed/NCBI
32	Shalaby F, Rossant J, Yamaguchi TP, Gertsenstein M, Wu XF, Breitman ML and Schuh AC: Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice. Nature. 376:62–66. 1995. View Article : Google Scholar : PubMed/NCBI
33	Ranayhossaini DJ, Rodriguez AI, Sahoo S, Chen BB, Mallampalli RK, Kelley EE, Csanyi G, Gladwin MT, Romero G and Pagano PJ: Selective Recapitulation of conserved and Nonconserved regions of putative NOXA1 protein activation domain confers isoform-specific inhibition of Nox1 oxidase and attenuation of endothelial cell migration. J Biol Chem. 288:36437–36450. 2013. View Article : Google Scholar : PubMed/NCBI
34	Makinen T, Jussila L, Veikkola T, Karpanen T, Kettunen MI, Pulkkanen KJ, Kauppinen R, Jackson DG, Kubo H, Nishikawa S, et al: Inhibition of lymphangiogenesis with resulting lymphedema in transgenic mice expressing soluble VEGF receptor-3. Nat Med. 7:199–205. 2001. View Article : Google Scholar : PubMed/NCBI
35	Hogan BM, Herpers R, Witte M, Heloterä H, Alitalo K, Duckers HJ and Schulte-Merker S: Vegfc/Flt4 signalling is suppressed by Dll4 in developing zebrafish intersegmental arteries. Development. 136:4001–4009. 2009. View Article : Google Scholar : PubMed/NCBI
36	Park JA, Kim DY, Kim YM, Lee IK and Kwon YG: Endothelial snail regulates capillary branching morphogenesis via vascular endothelial growth factor receptor 3 expression. PLoS Genet. 11:e10053242015. View Article : Google Scholar : PubMed/NCBI
37	Clarkin CE and Gerstenfeld LC: VEGF and bone cell signalling: An essential vessel for communication? Cell Biochem Funct. 31:1–11. 2013. View Article : Google Scholar : PubMed/NCBI
38	Moslehi JJ: Cardiovascular toxic effects of targeted cancer therapies. New Engl J Med. 375:1457–1467. 2016. View Article : Google Scholar : PubMed/NCBI