Signaling pathways involved in vascular smooth muscle cell calcification during hyperphosphatemia

Jakob Voelkl, Florian Lang, Kai Uwe Eckardt, Kerstin Amann, Makoto Kuro-o, Andreas Pasch, Burkert Pieske, Ioana Alesutan

Research output: Contribution to journalReview articlepeer-review

117 Scopus citations


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.

Original languageEnglish (US)
JournalCellular and Molecular Life Sciences
StatePublished - Jan 1 2019


  • CKD
  • Osteogenic signaling
  • Phosphate
  • Vascular calcification
  • Vascular smooth muscle cells

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Cellular and Molecular Neuroscience
  • Cell Biology


Dive into the research topics of 'Signaling pathways involved in vascular smooth muscle cell calcification during hyperphosphatemia'. Together they form a unique fingerprint.

Cite this