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Abstract: TH-PO530

Macrophage Migrasomes Is a Crucial Determinant of Subcutaneous Microvascular Calcifications in Patients with Calciphylaxis

Session Information

Category: Bone and Mineral Metabolism

  • 401 Bone and Mineral Metabolism: Basic

Authors

  • Zhu, Xiaodong, Institute of Nephrology, Zhong Da Hospital, Southeast University, School of Medicine, Nanjing, China
  • Liu, Yuqiu, Institute of Nephrology, Zhong Da Hospital, Southeast University, School of Medicine, Nanjing, China
  • Xie, Xiaotong, Institute of Nephrology, Zhong Da Hospital, Southeast University, School of Medicine, Nanjing, China
  • Ni, Haifeng, Institute of Nephrology, Zhong Da Hospital, Southeast University, School of Medicine, Nanjing, China
  • Tang, Ri-ning, Institute of Nephrology, Zhong Da Hospital, Southeast University, School of Medicine, Nanjing, China
  • Wu, Beibei, Institute of Nephrology, Zhong Da Hospital, Southeast University, School of Medicine, Nanjing, China
  • Liu, Bi-Cheng, Institute of Nephrology, Zhong Da Hospital, Southeast University, School of Medicine, Nanjing, China
  • Zhang, Xiaoliang, Institute of Nephrology, Zhong Da Hospital, Southeast University, School of Medicine, Nanjing, China
Background

Calciphylaxis is rare syndrome in hemodialysis patients who typically manifest as subcutaneous microvascular calcifications. Macrophage has been proposed to a prime mediator of calciphylaxis. However, the pathogenesis remains unclear. Here, we document that macrophage produce a previously unrecognized nanostructures called “migrasomes” (M-mig), which involve in microvascular calcifications in calciphylaxis.

Methods

Skin biopsy specimens from patients with calciphylaxis (n=34) were collected. The possible relation between M-mig and subcutaneous microvascular calcifications was studied. The stray artery from experimental mice were treated with M-mig under high Ca/P stimulation or hemodialysis patientserum. The calcifying M-mig were assessed by TEM, Energy dispersive spectroscopy and Fluo-3 staining.

Results

Ultrastructural analysis revealed that macrophage produce a previously unrecognized nanostructures called M-mig (A. arrow) that originate from the filament like fibers (A. triangle). Pathology of skin biopsy surprisingly showed that macrophages infiltration (C. brown) was adjacent to the calcium deposition (D. green) in subcutaneous arteries which were rich in M-mig. Subsequently, TEM imaging revealed that mineral deposit in or on membrane of M-mig (B. asterisk). In murine model, when the stray artery incubated with M-mig under high level Ca/P or hemodialysis patient, serum, notablely, some mineral crystal enveloped M-mig and penetrated into inner lumen of the vascular wall, where microcalcifications deposition were observed by fine Fluo-3 staining. The microcalcifications were approved to correlation with calcific M-mig. In vitro, calcific M-mig showed a shift to larger size over time under high level Ca/P. Our study strongly suggests that M-mig could serve as the nucleating foci for mineralization and calcific M-mig initiates the microcalcification.

Conclusion

Our study documents that macrophages produce a formerly unrecognized nanostructure M-mig which involves in vascular microcalcifications. The discovery highlights the contribution of macrophages to vascular calcifications via M-mig and provides clues to the pathogenesis of calciphylaxis.

Funding

  • Government Support - Non-U.S.