Research progress on the role of Klotho in heart failure

doi:10.16352/j.issn.1001-6325.2023.06.0998

Abstract

Abstract: Klotho is an anti-aging protein and can be divided into three types: full-length transmembrane Klotho, soluble Klotho and secreted Klotho. Many studies have shown that Klotho is closely related to oxidative stress, inflammatory response, myocardial hypertrophy, fibrosis, autophagy, and mitochondrial dysfunction. It is also involved in the occurrence and development of heart failure. It is expected to provide a new target and direction for the treatment of heart failure.

Key words: Klotho, anti-aging protein, heart failure

CLC Number:

R542

CHAI Yaru, DENG Yuting, DAI Hongyan, GUAN Jun. Research progress on the role of Klotho in heart failure[J]. Basic & Clinical Medicine, 2023, 43(6): 998-1002.

References 25

[1]	Olejnik A, Krzywonos-Zawadzka A, Banaszkiewicz M, et al. Klotho protein contributes to cardioprotection during ischaemia/reperfusion injury[J]. J Cell Mol Med, 2020, 24: 6448-6458.
[2]	Xu Z, Zheng S, Feng X, et al. Klotho gene improves oxidative stress injury after myocardial infarction[J] 2021, 21: 52. doi: 10.3892/etm.2020.9484.
[3]	Oishi H, Doi S, Nakashima A, et al. Klotho overexpres-sion protects against renal aging along with suppression of transforming growth factor-β1 signaling pathways[J]. Am J Physiol Renal Physiol, 2021, 321: F799-F811.
[4]	Akasaka-Manya K, Manya H, Nadanaka S, et al. Decreased ADAM17 expression in the lungs of α-Klotho reduced mouse[J]. J Biochem, 2020, 167: 483-493.
[5]	Wang X, Zhang G, Dasgupta S, et al. ATF4 protects the heart from failure by antagonizing oxidative stress[J]. Circ Res, 2022, 131: 91-105.
[6]	Song S, Si LY. Klotho ameliorated isoproterenol-induced pathological changes in cardiomyocytes via the regulation of oxidative stress[J]. Life Sci, 2015, 135: 118-123.
[7]	Zhu H, Gao Y, Zhu S, et al. Klotho improves cardiac function by suppressing reactive oxygen species (ROS) mediated apoptosis by modulating Mapks/Nrf2 signaling in doxorubicin-induced cardiotoxicity[J]. Med Sci Monit, 2017, 23: 5283-5293.
[8]	Chen K, Wang S, Sun QW, et al. Klotho deficiency causes heart aging via impairing the Nrf2-GR pathway[J]. Circ Res, 2021, 128: 492-507.
[9]	Hui H, Zhai Y, Ao L, et al. Klotho suppresses the inflammatory responses and ameliorates cardiac dysfunction in aging endotoxemic mice[J]. Oncotarget, 2017, 8: 15663-15676.
[10]	Lv J, Chen J, Wang M, et al. Klotho alleviates indoxyl sulfate-induced heart failure and kidney damage by promoting M2 macrophage polarization[J]. Aging (Albany NY), 2020, 12: 9139-9150.
[11]	Wang Y, Wang K, Bao Y, et al. The serum soluble Klotho alleviates cardiac aging and regulates M2a/M2c macrophage polarization via inhibiting TLR4/Myd88/NF-κB pathway[J]. Tissue Cell, 2022, 76: 101812. doi: 10.1016/j.tice.2022.101812.
[12]	Xie J, Cha SK, An SW, et al. Cardioprotection by Klotho through downregulation of TRPC6 channels in the mouse heart[J]. Nat Commun, 2012, 3: 1238. doi: 10.1038/ncomms2240.
[13]	Tang G, Shen Y, Gao P, et al. Klotho attenuates isoproterenol-induced hypertrophic response in H9C2 cells by activating Na(+)/K(+)-ATPase and inhibiting the reverse mode of Na(+)/Ca(2+)-exchanger[J]. In Vitro Cell Dev Biol Anim, 2018, 54: 250-256.
[14]	Chen WY. Soluble alpha-Klotho alleviates cardiac fibrosis without altering cardiomyocytes renewal[J]. Int J Mol Sci, 2020, 21: 2186. doi: 10.3390/ijms21062186.
[15]	Ding J, Tang Q, Luo B, et al. Klotho inhibits angiotensin II-induced cardiac hypertrophy, fibrosis, and dysfunction in mice through suppression of transforming growth factor-β1 signaling pathway[J].Eur J Pharmacol, 2019, 859: 172549. doi: 10.1016/j.ejphar.2019.172549.
[16]	Li JM, Chen FF, Li GH, et al. Soluble Klotho-integrin β1/ERK1/2 pathway ameliorates myocardial fibrosis in diabetic cardiomyopathy[J].FEBS J, 2021, 35: e21960. doi: 10.1096/fj.202100952R.
[17]	Suassuna PGA, Cherem PM, de Castro BB, et al. αKlotho attenuates cardiac hypertrophy and increases myocardial fibroblast growth factor 21 expression in uremic rats[J]. Exp Biol Med (Maywood), 2020, 245: 66-78.
[18]	Gao G, Chen W, Yan M, et al. Rapamycin regulates the balance between cardiomyocyte apoptosis and autophagy in chronic heart failure by inhibiting mTOR signaling[J]. Int J Mol Med, 2020, 45: 195-209.
[19]	Liao LZ, Chen ZC, Wang SS, et al. Klotho deficiency causes cardiac ageing by impairing autophagic and activating apoptotic activity[J]. Eur J Pharmacol, 2021, 911: 174559. doi: 10.1016/j.ejphar.2021.174559.
[20]	Chang YW, Song ZH, Chen CC. FAK regulates cardiomyocyte mitochondrial fission and function through Drp1[J]. FEBS J, 2022, 289: 1897-1910.
[21]	Zhuang X, Sun X, Zhou H, et al. Klotho attenuated Doxorubicin-induced cardiomyopathy by alleviating Dynamin-related protein 1-mediated mitochondrial dysfunc-tion[J]. Meth Ageing Dev, 2021, 195: 111442. doi: 10.1016/j.mad.2021.111442.
[22]	Zhu X, Lu X, Yin T, et al. Renal function mediates the association between Klotho and congestive heart failure among middle-aged and older individuals[J]Front Cardiovasc Med, 2022, 9: 802287. doi: 10.3389/fcvm.2022.802287.
[23]	张志敏, 苟丽沙, 马丽群, 等. 达格列净降低心力衰竭大鼠心肌内质网应激并缓解左室重构.[J]. 基础医学与临床, 2021, 41: 1742-1748.
[24]	Kale A, Sankrityayan H, Anders HJ, et al. Klotho: A possible mechanism of action of SGLT2 inhibitors preventing episodes of acute kidney injury and cardiorenal complications of diabetes[J]. Drug Discov Today, 2021, 26: 1963-1971.
[25]	Taneike M, Nishida M, Nakanishi K, et al. Alpha-Klotho is a novel predictor of treatment responsiveness in patients with heart failure[J]. Sci Rep, 2021, 11: 2058. doi: 10.1038/s41598-021-81517-9.