The regulation of valvular and vascular sclerosis by osteogenic morphogens

Kristina I. Boström, Nalini M. Rajamannan, Dwight A. Towler

Research output: Contribution to journalReview articlepeer-review

165 Scopus citations

Abstract

Vascular calcification increasingly afflicts our aging, dysmetabolic population. Once considered only a passive process of dead and dying cells, vascular calcification has now emerged as a highly regulated form of biomineralization organized by collagenous and elastin extracellular matrices. During skeletal bone formation, paracrine epithelial-mesenchymal and endothelial-mesenchymal interactions control osteochondrocytic differentiation of multipotent mesenchymal progenitor cells. These paracrine osteogenic signals, mediated by potent morphogens of the bone morphogenetic protein and wingless-type MMTV integration site family member (Wnt) superfamilies, are also active in the programming of arterial osteoprogenitor cells during vascular and valve calcification. Inflammatory cytokines, reactive oxygen species, and oxylipids-increased in the clinical settings of atherosclerosis, diabetes, and uremia that promote arteriosclerotic calcification-elicit the ectopic vascular activation of osteogenic morphogens. Specific extracellular and intracellular inhibitors of bone morphogenetic protein-Wnt signaling have been identified as contributing to the regulation of osteogenic mineralization during development and disease. These inhibitory pathways and their regulators afford the development of novel therapeutic strategies to prevent and treat valve and vascular sclerosis.

Original languageEnglish (US)
Pages (from-to)564-577
Number of pages14
JournalCirculation research
Volume109
Issue number5
DOIs
StatePublished - Aug 19 2011

Keywords

  • BMP
  • Wnt
  • inflammation
  • osteoblast differentiation
  • vascular calcification

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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