Abstract
Background and PurposeVascular 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.MethodsTissue 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.ResultsSeventy-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.ConclusionsOPG (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.
Highlights
Arterial calcification (AC) is independently associated with increased cardiovascular morbidity and mortality [1], and its development in atheromatous lesions impacts deeply on plaque stability [2]
Giant multinucleated cells positive for tartrate-resistant acid phosphatase (TRAP) have been identified in atherosclerosis lesions [10]. They most likely originate from intraplaque macrophages, which have the ability to differentiate into osteoclast-like cells in the presence of RANK-Ligand [11]
Osteoid Metaplasia is a specific feature of asymptomatic carotid plaques Out of the 73 carotid plaques, osteoid metaplasia (OM) ( = bone-tissue) was noted in 18.4% (9/49) of the asymptomatic and in none (0/24, 0%) of the symptomatic carotid lesions (p = 0.02) (Fig. 1A and Table 1)
Summary
Arterial calcification (AC) is independently associated with increased cardiovascular morbidity and mortality [1], and its development in atheromatous lesions impacts deeply on plaque stability [2]. Giant multinucleated cells positive for tartrate-resistant acid phosphatase (TRAP) have been identified in atherosclerosis lesions [10]. They most likely originate from intraplaque macrophages, which have the ability to differentiate into osteoclast-like cells in the presence of RANK-Ligand [11]. Comprehension of the mechanisms underlying the formation of mineralized tissue within carotid atherosclerosis lesions is of high importance since calcification greatly influences the plaque stability and the consecutive risk of stroke [2,3,12]. 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
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
