Klotho: A Major Shareholder in Vascular Aging Enterprises
Abstract
:1. Introduction
2. The Biology of Klotho
2.1. Structure of Klotho
2.2. Tissue Expression of Klotho
2.3. The Klotho–FGF23 Axis
2.4. Klotho Exerts Pleiotropic Functions Independent of FGF23
3. Vasculo-Protective Effects of Klotho
3.1. Vascular Calcification
3.2. Endothelial Dysfunction
3.3. Oxidative Stress and Inflammation
4. Experimental Challenges and the Future of Klotho-Based Therapies
5. Summary
Funding
Conflicts of Interest
Disclosures
References
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Arterial Klotho Expression | Experimental Observations | Reference |
---|---|---|
Decreased mRNA and protein in human CKD | Human aorta Klotho deficiency in CKD can be reversed and calcification is attenuated ex vivo with VDRA | Lim et al. [13] |
Decreased mRNA and protein in CKD mice | Low aortic Klotho but high circulating Klotho associated with vascular calcification in ldlr -/- CKD mice | Fang et al. [78] |
mRNA but no protein in mouse aorta | Aortic Klotho has no role in vascular calcification | Lindberg et al. [79] |
mRNA in human aorta, coronary arteries and thrombus | Klotho mRNA detectable in human arteries and thrombi of occlusive coronary disease | Donate-Correa et al. [81] |
Increased mRNA and protein in calcified aorta of Enpp1-/- mice | Increased Klotho associated with decreased vascular calcification in CKD mice | Zhu et al. [82] |
mRNA and protein expression in rat aorta but not in rat vascular smooth muscle cells | No native VSMC Klotho expression, however overexpression worsens calcification | Jimbo et al. [50] |
No mRNA or protein expression in mouse aorta | VDRA in vivo increases plasma αKlotho an decreases vascular calcification in CKD mice | Lau et al. [69] |
No mRNA in normal and calcified aortas of CKD mice | No aortic Klotho expression and no Klotho effect in vitro | Scialla et al. [83] |
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Lim, K.; Halim, A.; Lu, T.-s.; Ashworth, A.; Chong, I. Klotho: A Major Shareholder in Vascular Aging Enterprises. Int. J. Mol. Sci. 2019, 20, 4637. https://doi.org/10.3390/ijms20184637
Lim K, Halim A, Lu T-s, Ashworth A, Chong I. Klotho: A Major Shareholder in Vascular Aging Enterprises. International Journal of Molecular Sciences. 2019; 20(18):4637. https://doi.org/10.3390/ijms20184637
Chicago/Turabian StyleLim, Kenneth, Arvin Halim, Tzong-shi Lu, Alan Ashworth, and Irene Chong. 2019. "Klotho: A Major Shareholder in Vascular Aging Enterprises" International Journal of Molecular Sciences 20, no. 18: 4637. https://doi.org/10.3390/ijms20184637