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Recent evidence indicates that intraleaflet haemorrhage (ILH) strongly promotes CAVD progression. However, it remains poorly understood how it mechanistically contributes to valvular calcification.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>ILH was identified as iron deposition by morphological analysis. To elucidate the underlying mechanism, human valvular interstitial cells (VIC) were cultured in the presence of fresh or senescent red blood cells (RBC), simulating ILH in vivo conditions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Result<\/jats:title>\n                    <jats:p>ILH was common in aortic valves derived from patients with severe aortic stenosis. VIC undergo erythrophagocytosis of senescent RBC, leading to intracellular iron accumulation analogous to observed following exposure to extracellular iron. The presence of senescent RBC significantly intensified VIC calcification, which was significantly mitigated by ferroptosis inhibition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our results identify erythrophagocytosis by VIC, leading to iron accumulation and enhanced calcification through ferroptosis. This may be a crucial component of the pathophysiological mechanisms that links ILH to valvular calcification and accelerated aortic stenosis progression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ehf2.15132","type":"journal-article","created":{"date-parts":[[2024,10,27]],"date-time":"2024-10-27T04:00:56Z","timestamp":1730001656000},"page":"1469-1473","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Increased Calcification by Erythrophagocytosis in Aortic Valvular Interstitial Cells"],"prefix":"10.1093","volume":"12","author":[{"given":"Zihan","family":"Qin","sequence":"first","affiliation":[{"name":"Translational Cardiology, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet , Stockholm 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