Role of Klotho in the Development of Essential Hypertension

Hypertension. 2021 Mar 3;77(3):740-750. doi: 10.1161/HYPERTENSIONAHA.120.16635. Epub 2021 Jan 11.

Abstract

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.

Keywords: albuminuria; aldosterone; inflammation; kidney diseases; serum.

Publication types

  • Review

MeSH terms

  • 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

Substances

  • FGF23 protein, human
  • Fgf23 protein, mouse
  • Fibroblast Growth Factors
  • Insulin-Like Growth Factor I
  • Fibroblast Growth Factor-23
  • Glucuronidase
  • Klotho Proteins