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Iron in Vascular Calcification: Pro-Calcific Agent or Protective Modulator?
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Iron in Vascular Calcification: Pro-Calcific Agent or Protective Modulator?
Iron in Vascular Calcification: Pro-Calcific Agent or Protective Modulator?
Journal Article

Iron in Vascular Calcification: Pro-Calcific Agent or Protective Modulator?

2025
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Overview
Vascular calcification is a complex, regulated process characterized by the pathological deposition of calcium phosphate minerals in the vascular wall, contributing to cardiovascular morbidity and mortality, particularly in patients with chronic kidney disease (CKD), diabetes, and aging. Once thought to be a passive degenerative process, it is now recognized as an active, cell-mediated phenomenon that shares molecular features with bone formation. Beyond traditional risk factors such as hyperphosphatemia and inflammation, disturbances in iron metabolism have recently emerged as modulators of vascular calcification. Iron, a vital trace element involved in numerous cellular functions, exhibits a dual role as both a potential driver and inhibitor of calcification, depending on its dose, distribution, and cellular context. In this review, we summarize in vitro and in vivo studies investigating the impact of iron on the osteochondrogenic differentiation and calcification of vascular smooth muscle cells and valve interstitial cells. We further highlight mechanistic insights that may explain the divergent findings reported in the literature. Finally, we compile clinical evidence linking disturbances in iron metabolism with coronary artery calcification and cardiovascular mortality in CKD patients.