The pathophysiology of vascular calcification: are osteoclast-like cells the missing link?
There is increasing evidence to suggest that the initiation of vascular calcification is an active process involving vascular smooth muscle cell (VSMC) apoptosis and trans-differentiation into calcifying cells. This active process results in the deposition of an osteogenic extracellular matrix and may be exacerbated by a reduction in the levels of one or more native calcification inhibitors (such as fetuin A and pyrophosphate). Here, we present data which strongly suggest that the regression of vascular calcification might also be an active cellular process involving osteoclast-like cells. However, the presence of osteoclast like cells in the vascular wall is rather limited. To explain this rarity of osteoclast-like cells, we recently observed that the same factors, which promote the trans-differentiation of VSMCs into osteoblast-like cells are also capable of inhibiting the in vitro differentiation of monocytes/macrophages into osteoclast-like cells. An imbalance between osteoblast-like and osteoclast-like cell activities would therefore favour the occurrence of a pathological calcification process in vessel walls. Our new data are strongly evocative of a vascular remodelling process similar to that observed in bone tissue. To confirm this hypothesis, strategies for activating osteoclasts in the vascular wall (with a view to preventing or reversing vascular calcifications) are required.
Massy
Z A
ZA
INSERM, ERI-12, 80054 Amiens, France. massy@u-picardie.fr
Mentaverri
R
R
Mozar
A
A
Brazier
M
M
Kamel
S
S
D001846:Bone Development; D001842:Bone and Bones / Q000473:pathology / Q000503:physiopathology; D002114:Calcinosis / Q000503:physiopathology*; D002318:Cardiovascular Diseases / Q000503:physiopathology*; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000473:pathology / Q000503:physiopathology*; D010010:Osteoclasts / Q000473:pathology / Q000502:physiology*