Regulatory mechanisms in vascular calcification

AP Sage, Y Tintut, LL Demer - Nature Reviews Cardiology, 2010 - nature.com
AP Sage, Y Tintut, LL Demer
Nature Reviews Cardiology, 2010nature.com
In the past decade, the prevalence, significance, and regulatory mechanisms of vascular
calcification have gained increasing recognition. Over a century ago, pathologists
recognized atherosclerotic calcification as a form of extraskeletal ossification. Studies are
now identifying the mechanism of this remarkable process as a recapitulation of embryonic
endochondral and membranous ossification through phenotypic plasticity of vascular cells
that function as adult mesenchymal stem cells. These embryonic developmental programs …
Abstract
In the past decade, the prevalence, significance, and regulatory mechanisms of vascular calcification have gained increasing recognition. Over a century ago, pathologists recognized atherosclerotic calcification as a form of extraskeletal ossification. Studies are now identifying the mechanism of this remarkable process as a recapitulation of embryonic endochondral and membranous ossification through phenotypic plasticity of vascular cells that function as adult mesenchymal stem cells. These embryonic developmental programs, involving bone morphogenetic proteins and potent osteochondrogenic transcription factors, are triggered and modulated by a variety of inflammatory, metabolic, and genetic disorders, particularly hyperlipidemia, chronic kidney disease, diabetes, hyperparathyroidism, and osteoporosis. They are also triggered by loss of powerful inhibitors, such as fetuin A, matrix Gla protein, and pyrophosphate, which ordinarily restrict biomineralization to skeletal bone. Teleologically, soft-tissue calcification might serve to create a wall of bone to sequester noxious foci such as chronic infections, parasites, and foreign bodies. This Review focuses on atherosclerotic and medial calcification. The capacity of the vasculature to produce mineral in culture and to produce de novo, vascularized, trabecular bone and cartilage tissue, even in patients with osteoporosis, should intrigue investigators in tissue engineering and regenerative biology.
nature.com