Osteoprotegerin and bone-like vascular calcification are predictive markers of vulnerable carotid plaques

Marie Francoise Heymann; Jean Michel Davaine; Olivier Laperine; Thierry Merlini; Beatrice Guyomarch; Mathias Chatelais; Florian Guilbaud; Meadhbh Aine Brennan; Dominique Heymann; Yann Goueffic

doi:10.1530/boneabs.3.PP375

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Bone Abstracts (2014) 3 PP375 | DOI: 10.1530/boneabs.3.PP375

ECTS2014 Poster Presentations Other diseases of bone and mineral metabolism (44 abstracts)

Osteoprotegerin and bone-like vascular calcification are predictive markers of vulnerable carotid plaques

Marie Francoise Heymann ^1, , Jean Michel Davaine ^1, , Olivier Laperine ^1, , Thierry Merlini ^1, , Beatrice Guyomarch ^2, , Mathias Chatelais ^1, , Florian Guilbaud ^1, , Meadhbh Aine Brennan ^1, , Dominique Heymann ^1, & Yann Goueffic ^1,

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¹INSERM UMR957, Nantes, France; ²University Hospital, Nantes, France; ³Institut du Thorax, Nantes, France.

Vascular calcification has a marked impact on arterial heterogeneity and plaque stability. Based on a cohort of 116 patients (carotid and femoral endarterectomies), the aim of the present study was to determine the influence of the bone-like vascular calcification and of osteoprotegerin (OPG) on plaque stability.

Seventy-three carotid and 43 femoral plaques along with plasma were harvested and analyzed in a single center study. The presence of osteoid metaplasia (bone-like vascular calcification) was significantly higher in femoral compared to carotid plaques (P<0.01) and in asymptomatic vs symptomatic carotid plaques (P<0.01). OPG staining was significantly higher in carotid than in femoral plaques (P<0.05) and in asymptomatic vs symptomatic carotid lesions (P<0.05). Circulating OPG levels were significantly higher in the asymptomatic carotid group compared to the symptomatic carotid group. In vitro, human pericytes secreted high amounts of OPG and differentiated in osteoblasts. In pro-inflammatory conditions, pericytes induced an imbalance between osteoblast- and osteoclast-precursor differentiation towards mineral formation in which OPG appeared strongly involved.

These results indicate that circulating OPG should be considered as a promising predictive marker for carotid plaque vulnerability. Furthermore, the presence of intense intraplaque vascular pericytes and OPG infiltration was associated with a higher presence of OM and with a significantly more stable phenotype of carotid plaques. Our in vitro findings indicate that pericytes may be strongly implicated in bone-like vascular formation.