Table 1.

The verified and potential mechanisms for cardiovascular protection of Klotho in CKD

Animal model	Outcome of CVD	Mechanism	Reference
EFmKL46 (Tg-K1) mice	VC	Inhibition of Pi influx into VSMC	Hu et al., 2011 [48]
Klotho−/– mice + rapamycin	VC	Inhibition of mammalian target of rapamycin (mTOR)	Zhao et al., 2015 [110]
NaPi2a−/–/Klotho−/– mice	VC	Regulating the phosphate associated co-transporter	Ohnishi et al., 2009a [51]
Cyp27b1−/–/Klotho−/– mice	VC	Reducing vitamin D levels through inactivation of Cyp27b1 activity	Ohnishi et al., 2009b [52]
Uremic mice + Klotho i.p.	LVH	Blocking Nox2/Nox4-derived ROS production and inhibiting p38 and ERK1/2 signaling pathways	Yang et al., 2015 [6]
Diabetic mice + Klotho i.p.	LVH	Suppressing cardiac inflammatory cytokines and oxidative stress	Guo et al., 2018 [68]
Uremic rats + rKlotho	LVH	Increasing myocardial fibroblast growth factor 21 expression	Suassuna et al., 2020 [73]
Mice received subcutaneous injections of Ang II + Klotho	LVH	Modifying the TGF-β1-miR-132 axis	Ding et al., 2019 [67]
Klotho−/– mice	AS	Regulating TRPC-1-mediated Ca2+ entry	Kusaba et al., 2016 [20]
OLETF rats + Ad-Klotho	AS	Increasing nitric oxide production	Saito et al., 2000 [111]
DKD mice + pcMV-Klotho	AS	Inhibiting macrophage M1 polarization and inducing macrophage M2 polarization	Jia et al., 2019 [95]
CKD mice + Klotho i.p.	AS	Inhibiting platelet hyperactivity	Yang et al., 2017 [7]

AS, atherosclerosis; CVD, cardiovascular disease; LVH, left ventricular hypertrophy; VC, vascular calcification.