The Influence of Calcification Factors and Endothelial-Dysfunction Factors on the Development of Unstable Atherosclerotic Plaques

Abstract

Background: This study aimed to evaluate changes in markers of calcification and of endothelial dysfunction during the development of calcification and instability of atherosclerotic plaques and to identify associations of calcification factors with the formation of unstable plaques. Methods: We analyzed 44 male patients with coronary atherosclerosis who underwent endarterectomy in coronary arteries during coronary bypass surgery. The endarterectomy material (intima/media) was examined using histological and biochemical methods, and the stability and calcification degree of atherosclerotic plaques were assessed. In homogenates of the tissue samples and in blood, concentrations of osteoprotegerin, osteocalcin, osteopontin, osteonectin, monocyte-chemoattractant protein type 1 (MCP-1), soluble vascular cell adhesion molecule 1 (sVCAM-1), and E-selectin were determined by enzyme immunoassays. Results: Unstable atherosclerotic plaques proved to be calcified more frequently (80.4% of plaques) than stable ones (45.0%). Osteonectin, E-selectin, and sVCAM-1 levels were lower in unstable plaques and plaques with large calcification deposits. Osteocalcin content increased with the increasing size of the calcification deposits in plaque. Blood osteocalcin concentration directly correlated with osteocalcin concentration in atherosclerotic plaques and was higher in the blood of patients with calcified plaques in coronary arteries. Conclusions: The results provide the basis for further research on the suitability of osteocalcin as a potential biomarker of an unstable calcified atherosclerotic plaque in a coronary artery.

The Effect of PCSK9 Inhibition on the Stabilization of Atherosclerotic Plaque Determined by Biochemical and Diagnostic Imaging Methods

“…The results of our study showed that a higher level of OPN concentration was present in patients whose atherosclerotic plaque was more stable on MRI (Type IV and V according to the AHA) [65]. Similar results have been reported by Polonskaya Y et al They showed that OPN levels are lower in unstable plaques in patients who undergo endarterectomy during coronary bypass surgery [66]. In turn, findings by Kadoglou et al suggest the notion that OPN down-regulates plaque calcification and may promote plaque instability as assessed by Gray-scale and color Doppler ultrasound examination [67].…”

Osteocalcin association with vascular function in chronic kidney disease

“…Alexander Tacey and associates 38 30,40,41 Among patients undergoing coronary bypass surgery, their blood OCN concentrations correlated with OCN levels in coronary atherosclerotic plaques and were higher in patients with calcified coronary plaques; in addition, OCN content increased with the size of the calcification deposits in plaque. 42 Recent studies have reported that OCN-expressing endothelial progenitor cells may involve vessel stiffness; they are generated in the bone marrow and secreted into vascular regions impaired by ischemia or endothelial dysfunction and mediate abnormal repair. 43,44 In vivo rat model of vitamin D induced vascular calcification revealed a correlation between elevated OCN levels.…”

Bone Health in Patients with Dyslipidemias: An Underestimated Aspect

“…Apart from bones, OPN appears to be involved in vascular inflammation and atherosclerosis [67]. Several lines of evidence suggest that OPN promotes atherosclerotic plaque formation, leading to artery calcification [68][69][70]. In patients with CHD, OPN was found to be localized in calcified atherosclerotic lesions [59] and calcified cardiac valves [71].…”