Generic placeholder image

Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Research Article

Curcumin Reduces Hypoxia/Reperfusion Injury of Cardiomyocytes by Stimulating Vascular Endothelial Cells to Secrete FGF2

Author(s): Jian-kun Cui, Mingming Fan and Qinwen Wang*

Volume 27, Issue 14, 2024

Published on: 08 November, 2023

Page: [2101 - 2109] Pages: 9

DOI: 10.2174/0113862073239166231103102648

Price: $65

Abstract

Objective: Endothelial cells (ECs) can provide cell protection for cardiomyocytes (CMs) under hypoxia-reoxygenation (HR) conditions by secreting derived factors. This study aimed to explore the role of curcumin (CUR) in ECs for protecting CMs from HR injury.

Methods: A co-culture system for ECs and CMs was set up, and subjected to HR. The transcription, expression, and secretion of FGF2 were detected by RT-qPCR, western blot, and ELISA, respectively. siRNAs specifically targeting FGF2 were transfected into ECs. FGF2 receptor- specific inhibitors (AZD4547) were used to treat CMs.

Results: The co-culture with ECs did not affect the proliferation of CMs, while CUR and ECs co-culture had a synergistic effect on promoting the proliferation of CMs in HR. Furthermore, the co-culture with ECs did not affect the apoptosis and autophagy of CMs in HR. However, the co-culture of ECs after CUR treatment inhibited the apoptosis and autophagy of CMs in HR. CUR treatment significantly enhanced FGF2 mRNA, protein, and secretion levels of ECs in HR. In addition, CUR treatment increased FGF2 levels in the CMs medium in the ECs and CMs co-culture system. The reduction of FGF2 levels in the medium and the inhibition of FGF2 receptors significantly inhibited the proliferation of CMs and significantly promoted the apoptosis and autophagy of CMs in HR.

Conclusion: Focusing on the protective effects of CUR and ECs on cardiomyocytes is of great significance for the treatment of clinical myocardial HR injury.

Graphical Abstract

[1]
Bosnjak, Z.J.; Ge, Z.D. The application of remote ischemic conditioning in cardiac surgery. F1000 Res., 2017, 6, 928.
[http://dx.doi.org/10.12688/f1000research.11018.1] [PMID: 28690837]
[2]
Hernández-Reséndiz, S.; Muñoz-Vega, M.; Contreras, W.E.; Crespo-Avilan, G.E.; Rodriguez-Montesinos, J.; Arias-Carrión, O.; Pérez-Méndez, O.; Boisvert, W.A.; Preissner, K.T.; Cabrera-Fuentes, H.A. Responses of endothelial cells towards ischemic conditioning following acute myocardial infarction. Cond. Med., 2018, 1(5), 247-258.
[PMID: 30338315]
[3]
Yu, H.; Kalogeris, T.; Korthuis, R.J. Reactive species-induced microvascular dysfunction in ischemia/reperfusion. Free Radic. Biol. Med., 2019, 135, 182-197.
[http://dx.doi.org/10.1016/j.freeradbiomed.2019.02.031] [PMID: 30849489]
[4]
Leucker, T.M.; Ge, Z.D.; Procknow, J.; Liu, Y.; Shi, Y.; Bienengraeber, M.; Warltier, D.C.; Kersten, J.R. Impairment of endothelial-myocardial interaction increases the susceptibility of cardiomyocytes to ischemia/reperfusion injury. PLoS One, 2013, 8(7), e70088.
[http://dx.doi.org/10.1371/journal.pone.0070088] [PMID: 23894596]
[5]
Liu, Y.; Paterson, M.; Baumgardt, S.L.; Irwin, M.G.; Xia, Z.; Bosnjak, Z.J.; Ge, Z.D. Vascular endothelial growth factor regulation of endothelial nitric oxide synthase phosphorylation is involved in isoflurane cardiac preconditioning. Cardiovasc. Res., 2019, 115(1), 168-178.
[http://dx.doi.org/10.1093/cvr/cvy157] [PMID: 29931049]
[6]
Zicola, E.; Arrigo, E.; Mancardi, D. H2S pretreatment is promigratory and decreases ischemia/reperfusion injury in human microvascular endothelial cells. Oxid. Med. Cell. Longev., 2021, 2021, 1-13.
[http://dx.doi.org/10.1155/2021/8886666] [PMID: 33953839]
[7]
Yang, Q.; He, G.W.; Underwood, M.J.; Yu, C.M. Cellular and molecular mechanisms of endothelial ischemia/reperfusion injury: Perspectives and implications for postischemic myocardial protection. Am. J. Transl. Res., 2016, 8(2), 765-777.
[PMID: 27158368]
[8]
Shahane, K.; Kshirsagar, M.; Tambe, S.; Jain, D.; Rout, S.; Ferreira, M.K.M.; Mali, S.; Amin, P.; Srivastav, P.P.; Cruz, J.; Lima, R.R. An updated review on the multifaceted therapeutic potential of Calendula officinalis L. Pharmaceuticals (Basel), 2023, 16(4), 611.
[http://dx.doi.org/10.3390/ph16040611] [PMID: 37111369]
[9]
Carmo Bastos, M.L.; Silva-Silva, J.V.; Neves Cruz, J.; Palheta da Silva, A.R.; Bentaberry-Rosa, A.A.; da Costa Ramos, G.; de Sousa Siqueira, J.E.; Coelho-Ferreira, M.R.; Percário, S.; Santana Barbosa Marinho, P.; Marinho, A.M.R.; de Oliveira Bahia, M.; Dolabela, M.F. Alkaloid from Geissospermum sericeum benth. & hook.f. ex miers (apocynaceae) induce apoptosis by caspase pathway in human gastric cancer cells. Pharmaceuticals (Basel), 2023, 16(5), 765.
[http://dx.doi.org/10.3390/ph16050765] [PMID: 37242548]
[10]
Lima, A.M.; Siqueira, A.S.; Möller, M.L.S.; Souza, R.C.; Cruz, J.N.; Lima, A.R.J.; Silva, R.C.; Aguiar, D.C.F.; Junior, J.L.S.G.V.; Gonçalves, E.C. In silico improvement of the cyanobacterial lectin microvirin and mannose interaction. J. Biomol. Struct. Dyn., 2022, 40(3), 1064-1073.
[http://dx.doi.org/10.1080/07391102.2020.1821782] [PMID: 32990187]
[11]
Boarescu, P.M.; Boarescu, I. Bocșan, I.C.; Pop, R.M.; Gheban, D.; Bulboacă, A.E.; Nicula, C.; Râjnoveanu, R.M.; Bolboacă, S.D. Curcumin nanoparticles protect against isoproterenol induced myocardial infarction by alleviating myocardial tissue oxidative stress, electrocardiogram, and biological changes. Molecules, 2019, 24(15), 2802.
[http://dx.doi.org/10.3390/molecules24152802] [PMID: 31374848]
[12]
Li, Y.; Tian, L.; Sun, D.; Yin, D. Retracted: Curcumin ameliorates atherosclerosis through upregulation of miR-126. J. Cell. Physiol., 2019, 234(11), 21049-21059.
[http://dx.doi.org/10.1002/jcp.28708] [PMID: 31016760]
[13]
Jiankun, Cui. N.G.; Meng, F.; Shi, L.; Tian, G.; Yang, G. Demethoxycurcumin regulates autophagy through PI3K-Akt-mTOR signaling pathway to protect myocardial ischemia-reperfusion injury in rats. J. Chin. Med., 2020, 48(8), 5.
[http://dx.doi.org/10.19664/j.cnki.1002-2392.200137]
[14]
Luo, R.; Zhao, L.; Li, S.; Chen, P.; Wang, L.; Yu, H.; Cai, K.; Yu, Q.; Tian, W. Curcumin alleviates palmitic acid-induced LOX-1 upregulation by suppressing endoplasmic reticulum stress in HUVECs. BioMed Res. Int., 2021, 2021, 1-13.
[http://dx.doi.org/10.1155/2021/9983725] [PMID: 34471643]
[15]
Zhou, X.; Afzal, S.; Zheng, Y.F.; Münch, G.; Li, C.G. Synergistic protective effect of curcumin and resveratrol against oxidative stress in endothelial EAhy926 cells. Evid. Based Complement. Alternat. Med., 2021, 2021, 1-13.
[http://dx.doi.org/10.1155/2021/2661025] [PMID: 34518768]
[16]
Manning, J.R.; Perkins, S.O.; Sinclair, E.A.; Gao, X.; Zhang, Y.; Newman, G.; Pyle, W.G.; Schultz, J.E.J. Low molecular weight fibroblast growth factor-2 signals via protein kinase C and myofibrillar proteins to protect against postischemic cardiac dysfunction. Am. J. Physiol. Heart Circ. Physiol., 2013, 304(10), H1382-H1396.
[http://dx.doi.org/10.1152/ajpheart.00613.2012] [PMID: 23479264]
[17]
Murphy, E.; Steenbergen, C. Mechanisms underlying acute protection from cardiac ischemia-reperfusion injury. Physiol. Rev., 2008, 88(2), 581-609.
[http://dx.doi.org/10.1152/physrev.00024.2007] [PMID: 18391174]
[18]
Xiao, J.; Lv, Y.; Lin, S.; Jin, L.; Zhang, Y.; Wang, X.; Ma, J.; Hu, K.; Feng, W.; Cai, L.; Li, X.; Tan, Y. Cardiac protection by basic fibroblast growth factor from ischemia/reperfusion-induced injury in diabetic rats. Biol. Pharm. Bull., 2010, 33(3), 444-449.
[http://dx.doi.org/10.1248/bpb.33.444] [PMID: 20190407]
[19]
Sun, Y.; Xu, H.; Xu, X.; Wang, H.; Yuan, Y.; An, Z.; Xu, Z.; Wang, G. A novel method to obtain rat aortic media for primary culture of rat aortic smooth muscle cells. In Vitro Cell. Dev. Biol. Anim., 2021, 57(7), 726-734.
[http://dx.doi.org/10.1007/s11626-021-00615-0] [PMID: 34462813]
[20]
Chen, X.; Tong, G.; Chen, S. Basic fibroblast growth factor protects against liver ischemia-reperfusion injury via the Nrf2/Hippo signaling pathway. Tissue Cell, 2022, 79, 101921.
[http://dx.doi.org/10.1016/j.tice.2022.101921] [PMID: 36150335]
[21]
Villanueva, S.; Cespedes, C.; Gonzalez, A.; Vio, C.P. bFGF induces an earlier expression of nephrogenic proteins after ischemic acute renal failure. Am. J. Physiol. Regul. Integr. Comp. Physiol., 2006, 291(6), R1677-R1687.
[http://dx.doi.org/10.1152/ajpregu.00023.2006] [PMID: 16873559]
[22]
Villanueva, S.; Cespedes, C.; Gonzalez, A.A.; Roessler, E.; Vio, C.P. Inhibition of bFGF-receptor type 2 increases kidney damage and suppresses nephrogenic protein expression after ischemic acute renal failure. Am. J. Physiol. Regul. Integr. Comp. Physiol., 2008, 294(3), R819-R828.
[http://dx.doi.org/10.1152/ajpregu.00273.2007] [PMID: 18184769]
[23]
Chen, P.; Zhang, H.; Zhang, Q.; Zhou, W.; Deng, Y.; Hu, X.; Zhang, L. Basic fibroblast growth factor reduces permeability and apoptosis of human brain microvascular endothelial cells in response to oxygen and glucose deprivation followed by reoxygenation via the fibroblast growth factor receptor 1 (FGFR1)/ERK pathway. Med. Sci. Monit., 2019, 25, 7191-7201.
[http://dx.doi.org/10.12659/MSM.918626] [PMID: 31551405]
[24]
Bonfanti, R.; Musumeci, T.; Russo, C.; Pellitteri, R. The protective effect of curcumin in Olfactory Ensheathing Cells exposed to hypoxia. Eur. J. Pharmacol., 2017, 796, 62-68.
[http://dx.doi.org/10.1016/j.ejphar.2016.11.038] [PMID: 27889433]
[25]
Zhang, S.; Tang, D.; Zang, W.; Yin, G.; Dai, J.; Sun, Y.; Yang, Z.; Hoffman, R.M.; Guo, X. Synergistic inhibitory effect of traditional chinese medicine astragaloside IV and curcumin on tumor growth and angiogenesis in an orthotopic nude-mouse model of human hepatocellular carcinoma. Anticancer Res., 2017, 37(2), 465-474.
[http://dx.doi.org/10.21873/anticanres.11338] [PMID: 28179291]
[26]
Latimer, B.; Ekshyyan, O.; Nathan, N.; Moore-Medlin, T.; Rong, X.; Ma, X.; Khandelwal, A.; Christy, H.T.; Abreo, F.; McClure, G.; Vanchiere, J.A.; Caldito, G.; Dugas, T.; McMartin, K.; Lian, T.; Mehta, V.; Nathan, C.A. Enhanced systemic bioavailability of curcumin through transmucosal administration of a novel microgranular formulation. Anticancer Res., 2015, 35(12), 6411-6418.
[PMID: 26637850]
[27]
Wang, R.; Li, J.; Zhao, Y.; Li, Y.; Yin, L. Investigating the therapeutic potential and mechanism of curcumin in breast cancer based on RNA sequencing and bioinformatics analysis. Breast Cancer, 2018, 25(2), 206-212.
[http://dx.doi.org/10.1007/s12282-017-0816-6] [PMID: 29139094]
[28]
Tong, G.; Liang, Y.; Xue, M.; Chen, X.; Wang, J.; An, N.; Wang, N.; Chen, Y.; Wang, Y.; Jin, L.; Cong, W. The protective role of bFGF in myocardial infarction and hypoxia cardiomyocytes by reducing oxidative stress via Nrf2. Biochem. Biophys. Res. Commun., 2020, 527(1), 15-21.
[http://dx.doi.org/10.1016/j.bbrc.2020.04.053] [PMID: 32446359]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy