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Osteoprotegerin, pericytes and bone-like vascular calcification are associated with carotid plaque stability.

ABSTRACT: BACKGROUND AND PURPOSE: Vascular calcification, recapitulating bone formation, has a profound impact on plaque stability. The aim of the present study was to determine the influence of bone-like vascular calcification (named osteoid metaplasia?=?OM) and of osteoprotegerin on plaque stability. METHODS: Tissue from carotid endarterectomies were analysed for the presence of calcification and signs of vulnerability according to AHA grading system. Osteoprotegerin (OPG), pericytes and endothelial cells were sought using immuno-histochemistry. Symptoms and preoperative imaging findings (CT-scan, MRI and Doppler-scan) were analyzed. Human pericytes were cultured to evaluate their ability to secrete OPG and to influence mineralization in the plaque. RESULTS: Seventy-three carotid plaques (49 asymptomatic and 24 symptomatic) were harvested. A significantly higher presence of OM (18.4% vs 0%, p<0.01), OPG (10.2% of ROI vs 3.4% of ROI, p<0.05) and pericytes (19% of ROI vs 3.8% of ROI, p<0.05) were noted in asymptomatic compared to symptomatic plaques. Consistently, circulating OPG levels were higher in the plasma of asymptomatic patients (3.2 ng/mL vs 2.5 ng/mL, p?=?0.05). In vitro, human vascular pericytes secreted considerable amounts of OPG and underwent osteoblastic differentiation. Pericytes also inhibited the osteoclastic differentiation of CD14+ cells through their secretion of OPG. CONCLUSIONS: OPG (intraplaque an plasmatic) and OM are associated with carotid plaque stability. Pericytes may be involved in the secretion of intraplaque OPG and in the formation of OM.

SUBMITTER: Davaine JM

PROVIDER: S-EPMC4178031 | biostudies-other | 2014

REPOSITORIES: biostudies-other

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Osteoprotegerin, pericytes and bone-like vascular calcification are associated with carotid plaque stability.

Davaine Jean-Michel JM Quillard Thibaut T Brion Régis R Lapérine Olivier O Guyomarch Béatrice B Merlini Thierry T Chatelais Mathias M Guilbaud Florian F Brennan Meadhbh Áine MÁ Charrier Céline C Heymann Dominique D Gouëffic Yann Y Heymann Marie-Françoise MF

PloS one 20140926 9

<h4>Background and purpose</h4>Vascular calcification, recapitulating bone formation, has a profound impact on plaque stability. The aim of the present study was to determine the influence of bone-like vascular calcification (named osteoid metaplasia = OM) and of osteoprotegerin on plaque stability.<h4>Methods</h4>Tissue from carotid endarterectomies were analysed for the presence of calcification and signs of vulnerability according to AHA grading system. Osteoprotegerin (OPG), pericytes and en ...[more]

PMID: 25259713

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Project description:Background and purposeCarotid intraplaque hemorrhage is associated with stroke, plaque thickness, stenosis, ulceration, and adventitial inflammation. Conflicting data exist on whether calcification is a marker of plaque instability, and no data exist on adventitial calcification. Our goal was to determine whether adventitial calcification and soft plaque (a rim sign) help predict carotid intraplaque hemorrhage.Materials and methodsThis was a retrospective cohort study of 96 patients who underwent carotid MRA and CTA within 1 month, from 2009 to 2016. We excluded occlusions (n = 4) and near occlusions (n = 0), leaving 188 carotid arteries. Intraplaque hemorrhage was detected by using MPRAGE. Calcification, adventitial pattern, stenosis, maximum plaque thickness (total, soft, and hard), ulceration, and intraluminal thrombus on CTA were recorded. Atherosclerosis risk factors and medications were recorded. We used mixed-effects multivariable Poisson regression, accounting for 2 vessels per patient. For the final model, backward elimination was used with a threshold of P < .10. Receiver operating characteristic analysis determined intraplaque hemorrhage by using the area under the curve.ResultsOur final model included the rim sign (prevalence ratio = 11.9, P < .001) and maximum soft-plaque thickness (prevalence ratio = 1.2, P = .06). This model had excellent intraplaque hemorrhage prediction (area under the curve = 0.94), outperforming the rim sign, maximum soft-plaque thickness, NASCET stenosis, and ulceration (area under the curve = 0.88, 0.86, 0.77, and 0.63, respectively; P < .001). Addition of the rim sign performed better than each marker alone, including maximum soft-plaque thickness (area under the curve = 0.94 versus 0.86, P < .001), NASCET stenosis (area under the curve = 0.90 versus 0.77, P < .001), and ulceration (area under the curve = 0.90 versus 0.63, P < .001).ConclusionsThe CTA rim sign of adventitial calcification with internal soft plaque is highly predictive of carotid intraplaque hemorrhage.

Dataset Information

Osteoprotegerin, pericytes and bone-like vascular calcification are associated with carotid plaque stability.

Publications

Osteoprotegerin, pericytes and bone-like vascular calcification are associated with carotid plaque stability.

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