Cardiac Fibroblasts Adopt Osteogenic Fates and Can Be Targeted to Attenuate Pathological Heart Calcification.

Journal Article (Journal Article)

Mammalian tissues calcify with age and injury. Analogous to bone formation, osteogenic cells are thought to be recruited to the affected tissue and induce mineralization. In the heart, calcification of cardiac muscle leads to conduction system disturbances and is one of the most common pathologies underlying heart blocks. However the cell identity and mechanisms contributing to pathological heart muscle calcification remain unknown. Using lineage tracing, murine models of heart calcification and in vivo transplantation assays, we show that cardiac fibroblasts (CFs) adopt an osteoblast cell-like fate and contribute directly to heart muscle calcification. Small-molecule inhibition of ENPP1, an enzyme that is induced upon injury and regulates bone mineralization, significantly attenuated cardiac calcification. Inhibitors of bone mineralization completely prevented ectopic cardiac calcification and improved post injury heart function. Taken together, these findings highlight the plasticity of fibroblasts in contributing to ectopic calcification and identify pharmacological targets for therapeutic development.

Full Text

Duke Authors

Cited Authors

  • Pillai, ICL; Li, S; Romay, M; Lam, L; Lu, Y; Huang, J; Dillard, N; Zemanova, M; Rubbi, L; Wang, Y; Lee, J; Xia, M; Liang, O; Xie, Y-H; Pellegrini, M; Lusis, AJ; Deb, A

Published Date

  • February 2, 2017

Published In

Volume / Issue

  • 20 / 2

Start / End Page

  • 218 - 232.e5

PubMed ID

  • 27867037

Pubmed Central ID

  • PMC5291784

Electronic International Standard Serial Number (EISSN)

  • 1875-9777

Digital Object Identifier (DOI)

  • 10.1016/j.stem.2016.10.005


  • eng

Conference Location

  • United States