Role of Klotho in the Development of Essential Hypertension

Klotho has antiaging properties, and serum levels decrease with physiological aging and aging-related diseases, such as hypertension, cardiovascular, and chronic kidney disease. Klotho deficiency in mice results in accelerated aging and cardiovascular injury, whereas Klotho supplementation slows dow...

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Bibliographic Details
Published in:Hypertension (Dallas, Tex. 1979) Tex. 1979), 2021-03, Vol.77 (3), p.740-750
Main Authors: Kanbay, Mehmet, Demiray, Atalay, Afsar, Baris, Covic, Adrian, Tapoi, Laura, Ureche, Carina, Ortiz, Alberto
Format: Article
Language:English
Subjects:
Aging
Animals
Essential Hypertension - genetics
Essential Hypertension - metabolism
Essential Hypertension - physiopathology
Fibroblast Growth Factor-23
Fibroblast Growth Factors - genetics
Fibroblast Growth Factors - metabolism
Glucuronidase - genetics
Glucuronidase - metabolism
Humans
Insulin-Like Growth Factor I - genetics
Insulin-Like Growth Factor I - metabolism
Klotho Proteins
Mice
Mice, Knockout
Polymorphism, Single Nucleotide
Wnt Signaling Pathway - genetics
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Summary:Klotho has antiaging properties, and serum levels decrease with physiological aging and aging-related diseases, such as hypertension, cardiovascular, and chronic kidney disease. Klotho deficiency in mice results in accelerated aging and cardiovascular injury, whereas Klotho supplementation slows down the progression of aging-related diseases. The pleiotropic functions of Klotho include, but are not limited to, inhibition of insulin/IGF-1 (insulin-like growth factor 1) and WNT (wingless-related integration site) signaling pathways, suppression of oxidative stress and aldosterone secretion, regulation of calcium-phosphate homeostasis, and modulation of autophagy with inhibition of apoptosis, fibrosis, and cell senescence. Accumulating evidence shows an interconnection between Klotho deficiency and hypertension, and Klotho gene polymorphisms are associated with hypertension in humans. In this review, we critically review the current understanding of the role of Klotho in the development of essential hypertension and the most important underlying pathways involved, such as the FGF23 (fibroblast growth factor 23)/Klotho axis, aldosterone, Wnt5a/RhoA, and SIRT1 (Sirtuin1). Based on this critical review, we suggest avenues for further research.
ISSN:0194-911X
1524-4563
DOI:10.1161/HYPERTENSIONAHA.120.16635