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. 2021 Jan 28;7:617842. doi: 10.3389/fcvm.2020.617842

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Copyright © 2021 Saar-Kovrov, Donners and van der Vorst.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Local and systemic effects of soluble Klotho. Klotho is mainly expressed in the kidney where it interacts with FGF23 to regulate phosphate levels. By changing phosphate levels, Klotho for example has an effect on vascular calcification and possibly also on the heart. Additionally, Klotho is shed by shedding enzymes (e.g., ADAM10/ADAM17) generating soluble Klotho, either full-length or subfragment KL1 and KL2. Soluble Klotho has local effects in the kidney where it contributes to kidney function and in relation to this also CKD. Full-length soluble Klotho has been shown to have systemic effects on the vascular system by inducing anti-inflammatory effects and NO-induced vasodilatation. The exact effects of KL1 and KL2 on the vascular system remain to be determined. Furthermore, further research is needed to elucidate the exact systemic effects of full-length soluble Klotho as well as KL1 and KL2 on the heart. Figure is created with BioRender.com.