Macrophages highly express carbonic anhydrase 2 and play a significant role in demineralization of the ectopic calcification

Agian Jeffilano Barinda, Koji Ikeda, Ken Ichi Hirata, Noriaki Emoto

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

Vascular calcification is an important risk factor for cardiovascular disease, and is closely associated with all-cause mortality. Recently, it has been revealed that vascular calcification is not a passive precipitation of circulating minerals, but is a process actively regulated through machinery similar to bone formation. During the bone remodeling, osteoclasts execute the bone resorption by releasing hydrogen ions to dissolve minerals; however, molecular mechanisms underlying decalcification of ectopically calcified lesions remain largely unknown. Here, we identified a significant role of macrophages in decalcifying the ectopic calcification. Since carbonic anhydrase-2 (CA2) is critically involved in synthesizing hydrogen ions, we investigated its expression in various cells, and found that macrophages highly express CA2. We established a cell free assay system in which ectopic calcification is quantitatively analyzed in vitro, and using this assay system, we revealed that macrophages efficiently decalcify the ectopic calcification. Interestingly, M1 polarized macrophages showed reduced CA2 expression, whereas treatment with inflammatory cytokines and vasoactive peptides decreased CA2 expression in macrophages. Of note, treatment with angiotensin II significantly reduced the decalcification capacity in macrophages in association with reduced CA2 expression. Furthermore, overexpression of CA2 enhanced decalcification capacity in C2C12 myoblast cells. Together, we unveiled a potential role of macrophages in decalcifying the ectopic calcification, and identified that CA2 is critically involved in the cellular decalcification capacity. Activating cellular CA2 has a therapeutic potential in the treatment of ectopic calcification, especially in regressing vascular calcification.

Original languageEnglish
Pages (from-to)E45-E50
JournalKobe Journal of Medical Sciences
Volume63
Issue number2
Publication statusPublished - 2017

Keywords

  • Carbonic anhydrase 2
  • Decalcification
  • Ectopic calcification
  • Macrophage
  • Vascular calcification

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