BIOCHEMICAL MARKERS OF BONE TISSUE METABOLISM INFLUENCE ON VULNERABILITY OF ATHEROSCLEROTIC LESIONS

Aim. To assess some of biochemical markers of bone tissue metabolism, in vessel wall in males with coronary atherosclerosis; to evaluate the influence of these markers on vulnerability of atherosclerotic lesion and to figure out the specifics of their spread among unstable plaques of various kinds.

Material and methods. Totally, 65 males included at the age 46-79 y. o., admitted to the Clinics of E. N. Meshalkin Novosibirsk Scientific-Research Institute of Circulation Pathology for coronary bypass surgery. During operation, an endarterectomy was performed of coronary arteries. Each specimen of endarterectomy was symmetrically divided to fragments for histological and biochemical studies. By the results of histological analysis, in 193 specimens we found: 19 fragments of intact intima, 102 stable, 72 unstable plaques. Then the types of unstable plaques were established: 1) lipids’; 2) inflammatory-erosive; 3) distrophic-necrotic. In homogenates of the fragments we assessed: osteoprotegerin, calcitonin, osteocalcin, cholesterol. Statistics was done with SPSS (13.0).

Results. By the results of the performed histology, in unstable plaques there was higher level of calcification comparing to stable plaques. Biochemical studies showed increased levels of calcitonin and osteocalcin. If to assess the diverse types of unstable plaques, the highest level of these parameters was found in distrophic-necrotic plaques; lowest amount of calcitonin and osteocalcin was found in inflammatory-erosive type. Content of cholesterol in stable and unstable atherosclerotic lesions was about 4 times higher (p<0,01) in comparison with intact intima. Relation of cholesterol with calcitonin and osteocalcin was found, as well.

Conclusion. The data shows that increased osteoprotegerin aids the stabilization of lesion, and calcitonin and osteocalcin might be markers of plaque instability, caused by increased calcification.

1. Qiao JH, Mishra V, Fishbein MC, et al. Multinucleated giant cells in atherosclerotic plaques of human carotid arteries: Identification of osteoclast-like cells and their specific proteins in artery wall. Exp Mol Pathol 2015; 99 (3): 654-62.

2. Higgins CL, Isbilir S, Basto P, et al. Distribution of alkaline phosphate, osteopontin, RANK ligand and osteoprotogerin in calcified human carotid atheroma. Protein J. 2015; 34 (5): 315-28.

3. Ageev FT, Barinova IV, Seredina EM, et al. The formation mechanisms of calcification of the arteries. Cardiology Herald. 2012; VII (XIX): 57-63. Russian (Агеев Ф. Т., Баринова И. В., Середина И. М. и др. Механизмы формирования кальцификации артерий. Кардиологический вестник 2012; VII(XIX): 57-63.

4. Ragino YuI, Volkov AM, Chernyavskiy AM. Stages of development of atherosclerotic lesion and types of unstable plaques — pathophysiological and histological characteristics. Rus J Card. 2013; 5(103):88-95. Russian (Рагино Ю. И., Волков А. М., Чернявский А. М. Cтадии развития атеросклеротического очага и типы нестабильных бляшек — патофизиологическая и гистологическая характеристика. Российский кардиологичекий журнал 2013; 5(103): 88-95).

5. Han RI, Wheeler TM, Lumsden AB, et al. Morphometric analysis of calcification and fibrous layer thickness in carotid endarterectomy tissues. Comput Biol Med. 2016; 70: 210- 9.

6. Waksman R, Seruys PW. Handbook of the vulnerable plaque. London 2004.

7. Shlichkova TP, Zhdanov VS, Karpov YuA, et al. Main types of unstable atherosclerotic plaques and their prevalence in coronary arteries in acute myocardial infarction. Archives of pathology 2005; 3: 24-8. Russian (Шлычкова Т. П., Жданов В. С., Карпов Ю. А. и др. Основные типы нестабильных атеросклеротических бляшек и их распространенность в коронарных артериях при остром инфаркте миокарда. Архив патологии, 2005; 3: 24-8).

8. Polonskaya YaV, Kashtanova EV, Murashov IS, et al. The relationship of the main indicators of calcium and lipid exchange with atherosclerosis of the coronary arteries. Ateroskleroz i Dislipidemii 2015; 1: 24-8. Russian (Полонская Я. В., Каштанова Е. В., Мурашов И. С. и др. Взаимосвязь основных показателей кальциевого и липидного обмена с атеросклерозом коронарных артерий. Атеросклероз и дислипидемии 2015, 1: 24-8).

9. Wookey PJ, Zulli A, Hare DL. The elevated expression of calcitonin receptor by cells recruited into the endothelian layer and neo-intima of atherosclerotic plaque. Histochem Cell Biol. 2009 ; 132(2): 181-9.

10. Davaine J-M, Quillard T, Chatelais M, et al. Bone Like Arterial Calcification in Femoral Atherosclerotic Lesions: Prevalence and Role of Osteoprotegerin and Pericytes. Eur J Vasc Endovasc Surg 2016; 51: 259-67.

11. Schoppet M, Preissner KT, Hofbauer LC. RANK ligand and osteoprotegerin:paracrine regulators of bone metabolism and vascular function. Arterioscler Thromb Vasc Biol 2002; 22(4): 549-53.

12. Polonskaya YaV, Kashtanova EV, Stakhneva EM, et al. Association of osteocalcin and osteoprotegerin with inflammatory biomarkers in the vascular wall in men with coronary atherosclerosis. Abstracts of the Russian national Congress of cardiology 2015; 507, Russian (Полонская Я. В., Каштанова Е. В., Стахнёва Е. М. и др. Ассоциации остеокальцина и остеопротегерина с воспалительными биомаркерами в сосудистой стенке у мужчин с коронарным атеросклерозом. Тезисы Российского национального конгресса кардиологов 2015, 507).