Molecular mechanisms of vascular calcification: Lessons learned from the aorta

Jian Su Shao, Jun Cai, Dwight A. Towler

Research output: Contribution to journalReview article

260 Scopus citations

Abstract

Vascular calcification increasingly afflicts our aging and dysmetabolic population. Once considered a passive process, it has emerged as an actively regulated form of calcified tissue metabolism, resembling the mineralization of endochondral and membranous bone. Executive cell types familiar to bone biologists, osteoblasts, chondrocytes, and osteoclasts, are seen in calcifying macrovascular specimens. Lipidaceous matrix vesicles, with biochemical and ultrastructural "signatures" of skeletal matrix vesicles, nucleate vascular mineralization in diabetes, dyslipidemia, and uremia. Skeletal morphogens (bone morphogenetic protein-2 (BMP) and BMP4 and Wnts) divert aortic mesoangioblasts, mural pericytes (calcifying vascular cells), or valve myofibroblasts to osteogenic fates. Paracrine signals provided by these molecules mimic the epithelial-mesenchymal interactions that induce skeletal development. Vascular expression of pro-osteogenic morphogens is entrained to physiological stimuli that promote calcification. Inflammation, shear, oxidative stress, hyperphosphatemia, and elastinolysis provide stimuli that: (1) promote vascular BMP2/4 signaling and matrix remodeling; and (2) compromise vascular defenses that limit calcium deposition, inhibit osteo/chondrogenic trans-differentiation, and enhance matrix vesicle clearance. In this review, we discuss the biology of vascular calcification. We highlight how aortic fibrofatty tissue expansion (adventitia, valve interstitium), the adventitial-medial vasa, vascular matrix, and matrix vesicle metabolism contribute to the regulation of aortic calcium deposition, with greatest emphasis placed on diabetic vascular disease.

Original languageEnglish (US)
Pages (from-to)1423-1430
Number of pages8
JournalArteriosclerosis, thrombosis, and vascular biology
Volume26
Issue number7
DOIs
StatePublished - Jul 1 2006

Keywords

  • Bone morphogenetic proteins
  • Diabetes
  • Oxylipids
  • Vascular calcification
  • Wnt signaling

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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