Therapeutic Interference With Vascular Calcification-Lessons From Klotho-Hypomorphic Mice and Beyond

Frontiers in Endocrinology
Florian LangJakob Voelkl

Abstract

Medial vascular calcification, a major pathophysiological process associated with cardiovascular disease and mortality, involves osteo-/chondrogenic transdifferentiation of vascular smooth muscle cells (VSMCs). In chronic kidney disease (CKD), osteo-/chondrogenic transdifferentiation of VSMCs and, thus, vascular calcification is mainly driven by hyperphosphatemia, resulting from impaired elimination of phosphate by the diseased kidneys. Hyperphosphatemia with subsequent vascular calcification is a hallmark of klotho-hypomorphic mice, which are characterized by rapid development of multiple age-related disorders and early death. In those animals, hyperphosphatemia results from unrestrained formation of 1,25(OH)2D3 with subsequent retention of calcium and phosphate. Analysis of klotho-hypomorphic mice and mice with vitamin D3 overload uncovered several pathophysiological mechanisms participating in the orchestration of vascular calcification and several therapeutic opportunities to delay or even halt vascular calcification. The present brief review addresses the beneficial effects of bicarbonate, carbonic anhydrase inhibition, magnesium supplementation, mineralocorticoid receptor (MR) blockage, and ammonium salts. The case is mad...Continue Reading

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Citations

Nov 16, 2018·Journal of Investigative Medicine : the Official Publication of the American Federation for Clinical Research·Manuel Jiménez VillodresPedro Valdivielso
Apr 16, 2019·Current Opinion in Nephrology and Hypertension·Jakob VoelklIoana Alesutan
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Jun 4, 2020·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Ioana AlesutanJakob Voelkl
Jun 5, 2020·Vascular Health and Risk Management·Sepideh Zununi VahedMohammadreza Ardalan
Jan 23, 2021·Clinical Science·Trang Thi Doan LuongIoana Alesutan
May 4, 2021·Frontiers in Cell and Developmental Biology·Ángel MillánVíctor Sorribas
Aug 31, 2021·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Murray Epstein, Michael Freundlich

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