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Signaling pathways involved in vascular smooth muscle cell calcification during hyperphosphatemia
Signaling pathways involved in vascular smooth muscle cell calcification during hyperphosphatemia
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Signaling pathways involved in vascular smooth muscle cell calcification during hyperphosphatemia
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Signaling pathways involved in vascular smooth muscle cell calcification during hyperphosphatemia
Signaling pathways involved in vascular smooth muscle cell calcification during hyperphosphatemia
Journal Article

Signaling pathways involved in vascular smooth muscle cell calcification during hyperphosphatemia

2019
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Overview
Medial vascular calcification has emerged as a putative key factor contributing to the excessive cardiovascular mortality of patients with chronic kidney disease (CKD). Hyperphosphatemia is considered a decisive determinant of vascular calcification in CKD. A critical role in initiation and progression of vascular calcification during elevated phosphate conditions is attributed to vascular smooth muscle cells (VSMCs), which are able to change their phenotype into osteo-/chondroblasts-like cells. These transdifferentiated VSMCs actively promote calcification in the medial layer of the arteries by producing a local pro-calcifying environment as well as nidus sites for precipitation of calcium and phosphate and growth of calcium phosphate crystals. Elevated extracellular phosphate induces osteo-/chondrogenic transdifferentiation of VSMCs through complex intracellular signaling pathways, which are still incompletely understood. The present review addresses critical intracellular pathways controlling osteo-/chondrogenic transdifferentiation of VSMCs and, thus, vascular calcification during hyperphosphatemia. Elucidating these pathways holds a significant promise to open novel therapeutic opportunities counteracting the progression of vascular calcification in CKD.

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