Research progress of mechanisms of sclerostin in vascular calcification and atherosclerotic heart disease_West China Medical Journal

Authors：

YANG Hao , XU Jing , LI Fandan , DU Xiaoliang ,  Lü Zhan

Department of Cardiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P. R. China;

Corresponding?author：

Lü Zhan, Email: Doctor_LZ@163.com

Keywords：

Sclerostin; vascular calcification; atherosclerosis; cardiovascular disease

DOI：

10.7507/1002-0179.202409006

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Sclerostin, as a bone-derived secreted glycoprotein, is a suppressor of Wnt signaling pathway. Recently, adverse cardiovascular events in the treatment of osteoporosis with sclerostin inhibitors have raised concerns about the association of sclerostin with atherosclerotic heart disease. Whether the role of sclerostin in atherosclerotic heart disease is harmful or beneficial is not clear. This article reviews the progress of the mechanisms of sclerostin in vascular calcification and atherosclerotic heart disease, focusing on the relationship between sclerostin and vascular calcification, the impact of its concentration changes on atherosclerotic heart disease, and the effect of sclerostin inhibitor on cardiovascular events.

Citation： YANG Hao, XU Jing, LI Fandan, DU Xiaoliang, Lü Zhan. Research progress of mechanisms of sclerostin in vascular calcification and atherosclerotic heart disease. West China Medical Journal, 2024, 39(12): 1953-1957. doi: 10.7507/1002-0179.202409006 Copy

1.	Virani SS, Alonso A, Aparicio HJ, et al. Heart disease and stroke statistics-2021 update: a report from the American Heart Association. Circulation, 2021, 143(8): e254-e743.
2.	Lewiecki EM, Blicharski T, Goemaere S, et al. A phase III randomized placebo-controlled trial to evaluate efficacy and safety of romosozumab in men with osteoporosis. J Clin Endocrinol Metab, 2018, 103(9): 3183-3193.
3.	Catalano A, Bellone F, Morabito N, et al. Sclerostin and vascular pathophysiology. Int J Mol Sci, 2020, 21(13): 4779.
4.	Shui X, Dong R, Wu Z, et al. Association of serum sclerostin and osteoprotegerin levels with the presence, severity and prognosis in patients with acute myocardial infarction. BMC Cardiovasc Disord, 2022, 22(1): 213.
5.	Sem?nov M, Tamai K, HE X. SOST is a ligand for LRP5/LRP6 and a Wnt signaling inhibitor. J Biol Chem, 2005, 280(29): 26770-26775.
6.	孫婷婷, 王凱. 骨代謝相關因子參與動脈粥樣硬化的研究進展. 上海醫學, 2022, 45(2): 125-129.
7.	Khan K, Yu B, Tardif JC, et al. Significance of the Wnt signaling pathway in coronary artery atherosclerosis. Front Cardiovasc Med, 2024, 11: 1360380.
8.	Alrefaei AF, Abu-Elmagd M. LRP6 receptor plays essential functions in development and human diseases. Genes (Basel), 2022, 13(1): 120.
9.	Alesutan I, Henze LA, Boehme B, et al. Periostin augments vascular smooth muscle cell calcification via β-catenin signaling. Biomolecules, 2022, 12(8): 1157.
10.	De Maré A, Opdebeeck B, Neven E, et al. Sclerostin protects against vascular calcification development in mice. J Bone Miner Res, 2022, 37(4): 687-699.
11.	González-Salvatierra S, García-Fontana C, Lacal J, et al. Cardioprotective function of sclerostin by reducing calcium deposition, proliferation, and apoptosis in human vascular smooth muscle cells. Cardiovasc Diabetol, 2023, 22(1): 301.
12.	Wu CF, Liou HH, Kuo CC, et al. The association of urinary sclerostin and renal magnesium handling in type 2 diabetic patients with chronic kidney disease. Kidney Blood Press Res, 2021, 46(4): 514-522.
13.	羅靜, 王琰, 張瑞, 等. 慢性腎衰竭血液透析患者 IL-13、FGF23、SOST 水平變化與血管鈣化的關系. 西南醫科大學學報, 2024, 47(4): 325-329.
14.	殷雪嬌, 徐陽星, 徐秀容, 等. 血清骨膜蛋白和骨硬化蛋白對老年 2 型糖尿病患者骨質疏松的診斷價值. 中國現代醫學雜志, 2023, 33(1): 7-12.
15.	阮楊, 魏欣, 李群. 血清骨硬化蛋白、OPG、OPG/TRAIL 比值對高血壓伴慢性心力衰竭患者發生主要不良心血管事件的預測價值. 檢驗醫學與臨床, 2024, 21(13): 1945-1949, 1954.
16.	Olkowicz M, Czyzynska-Cichon I, Szupryczynska N, et al. Multi-omic signatures of atherogenic dyslipidaemia: pre-clinical target identification and validation in humans. J Transl Med, 2021, 19(1): 6.
17.	Krishna SM, Seto SW, Jose RJ, et al. Wnt signaling pathway inhibitor sclerostin inhibits angiotensin II-induced aortic aneurysm and atherosclerosis. Arterioscler Thromb Vasc Biol, 2017, 37(3): 553-566.
18.	Zheng J, Wheeler E, Pietzner M, et al. Lowering of circulating sclerostin may increase risk of atherosclerosis and its risk factors: evidence from a genome-wide association meta-analysis followed by Mendelian randomization. Arthritis Rheumatol, 2023, 75(10): 1781-1792.
19.	Staley JR, Giannakopoulou O, Holdsworth G, et al. Genetic data do not provide evidence that lower sclerostin is associated with increased risk of atherosclerosis: comment on the article by Zheng et al. Arthritis Rheumatol, 2023: 1-2.
20.	Koce?ak P, Puzianowska-Ku?nicka M, Olszanecka-Glinianowicz M, et al. Wnt signaling pathway and sclerostin in the development of atherosclerosis and vascular calcification. Adv Clin Exp Med, 2024, 33(5): 519-532.
21.	Leanza G, Cannata F, Faraj M, et al. Bone canonical Wnt signaling is downregulated in type 2 diabetes and associates with higher advanced glycation end-products (AGEs) content and reduced bone strength. Elife, 2024, 12: RP90437.
22.	González-Salvatierra S, García-Martín A, García-Fontana B, et al. Bone proteins are associated with cardiovascular risk according to the SCORE2-Diabetes algorithm. Cardiovasc Diabetol, 2024, 23(1): 311.
23.	譚艷飛, 譚艷美, 梅瑯. 血清骨硬化蛋白、內皮細胞特異性分子 1 與 2 型糖尿病亞臨床動脈粥樣硬化的關系. 中國動脈硬化雜志, 2022, 30(5): 410-415.
24.	Liu H, Guo Y, Zhu R, et al. Fructus Ligustri Lucidi preserves bone quality through induction of canonical Wnt/β‐catenin signaling pathway in ovariectomized rats. Phytother Res, 2021, 35(1): 424-441.
25.	Bovijn J, Krebs K, Chen CY, et al. Evaluating the cardiovascular safety of sclerostin inhibition using evidence from meta‐analysis of clinical trials and human genetics. Sci Transl Med, 2020, 12(549): eaay6570.
26.	Zhao B, Chen A, Wang H, et al. The relationship between sclerostin and carotid artery atherosclerosis in patients with stage 3-5 chronic kidney disease. Int Urol Nephrol, 2020, 52(7): 1329-1336.
27.	周琳, 李世軍. 冠心病與骨質疏松癥共病的機制與治療進展. 中國臨床保健雜志, 2023, 26(5): 712-717.
28.	Tsourdi E, Rachner TD, Hofbauer LC. Romosozumab versus alendronate and fracture risk in women with osteoporosis. N Engl J Med, 2018, 378(2): 195.
29.	Holdsworth G, Staley JR, Hall P, et al. Sclerostin downregulation globally by naturally occurring genetic variants, or locally in atherosclerotic plaques, does not associate with cardiovascular events in humans. J Bone Miner Res, 2021, 36(7): 1326-1339.
30.	Golledge J, Thanigaimani S. Role of sclerostin in cardiovascular disease. Arterioscler Thromb Vasc Biol, 2022, 42(7): e187-e202.
31.	Movérare-Skrtic S, Voelkl J, Nilsson KH, et al. Ohlsson C. B4GALNT3 regulates glycosylation of sclerostin and bone mass. EBioMedicine, 2023, 91: 104546.

1. Virani SS, Alonso A, Aparicio HJ, et al. Heart disease and stroke statistics-2021 update: a report from the American Heart Association. Circulation, 2021, 143(8): e254-e743.
2. Lewiecki EM, Blicharski T, Goemaere S, et al. A phase III randomized placebo-controlled trial to evaluate efficacy and safety of romosozumab in men with osteoporosis. J Clin Endocrinol Metab, 2018, 103(9): 3183-3193.
3. Catalano A, Bellone F, Morabito N, et al. Sclerostin and vascular pathophysiology. Int J Mol Sci, 2020, 21(13): 4779.
4. Shui X, Dong R, Wu Z, et al. Association of serum sclerostin and osteoprotegerin levels with the presence, severity and prognosis in patients with acute myocardial infarction. BMC Cardiovasc Disord, 2022, 22(1): 213.
5. Sem?nov M, Tamai K, HE X. SOST is a ligand for LRP5/LRP6 and a Wnt signaling inhibitor. J Biol Chem, 2005, 280(29): 26770-26775.
6. 孫婷婷, 王凱. 骨代謝相關因子參與動脈粥樣硬化的研究進展. 上海醫學, 2022, 45(2): 125-129.
7. Khan K, Yu B, Tardif JC, et al. Significance of the Wnt signaling pathway in coronary artery atherosclerosis. Front Cardiovasc Med, 2024, 11: 1360380.
8. Alrefaei AF, Abu-Elmagd M. LRP6 receptor plays essential functions in development and human diseases. Genes (Basel), 2022, 13(1): 120.
9. Alesutan I, Henze LA, Boehme B, et al. Periostin augments vascular smooth muscle cell calcification via β-catenin signaling. Biomolecules, 2022, 12(8): 1157.
10. De Maré A, Opdebeeck B, Neven E, et al. Sclerostin protects against vascular calcification development in mice. J Bone Miner Res, 2022, 37(4): 687-699.
11. González-Salvatierra S, García-Fontana C, Lacal J, et al. Cardioprotective function of sclerostin by reducing calcium deposition, proliferation, and apoptosis in human vascular smooth muscle cells. Cardiovasc Diabetol, 2023, 22(1): 301.
12. Wu CF, Liou HH, Kuo CC, et al. The association of urinary sclerostin and renal magnesium handling in type 2 diabetic patients with chronic kidney disease. Kidney Blood Press Res, 2021, 46(4): 514-522.
13. 羅靜, 王琰, 張瑞, 等. 慢性腎衰竭血液透析患者 IL-13、FGF23、SOST 水平變化與血管鈣化的關系. 西南醫科大學學報, 2024, 47(4): 325-329.
14. 殷雪嬌, 徐陽星, 徐秀容, 等. 血清骨膜蛋白和骨硬化蛋白對老年 2 型糖尿病患者骨質疏松的診斷價值. 中國現代醫學雜志, 2023, 33(1): 7-12.
15. 阮楊, 魏欣, 李群. 血清骨硬化蛋白、OPG、OPG/TRAIL 比值對高血壓伴慢性心力衰竭患者發生主要不良心血管事件的預測價值. 檢驗醫學與臨床, 2024, 21(13): 1945-1949, 1954.
16. Olkowicz M, Czyzynska-Cichon I, Szupryczynska N, et al. Multi-omic signatures of atherogenic dyslipidaemia: pre-clinical target identification and validation in humans. J Transl Med, 2021, 19(1): 6.
17. Krishna SM, Seto SW, Jose RJ, et al. Wnt signaling pathway inhibitor sclerostin inhibits angiotensin II-induced aortic aneurysm and atherosclerosis. Arterioscler Thromb Vasc Biol, 2017, 37(3): 553-566.
18. Zheng J, Wheeler E, Pietzner M, et al. Lowering of circulating sclerostin may increase risk of atherosclerosis and its risk factors: evidence from a genome-wide association meta-analysis followed by Mendelian randomization. Arthritis Rheumatol, 2023, 75(10): 1781-1792.
19. Staley JR, Giannakopoulou O, Holdsworth G, et al. Genetic data do not provide evidence that lower sclerostin is associated with increased risk of atherosclerosis: comment on the article by Zheng et al. Arthritis Rheumatol, 2023: 1-2.
20. Koce?ak P, Puzianowska-Ku?nicka M, Olszanecka-Glinianowicz M, et al. Wnt signaling pathway and sclerostin in the development of atherosclerosis and vascular calcification. Adv Clin Exp Med, 2024, 33(5): 519-532.
21. Leanza G, Cannata F, Faraj M, et al. Bone canonical Wnt signaling is downregulated in type 2 diabetes and associates with higher advanced glycation end-products (AGEs) content and reduced bone strength. Elife, 2024, 12: RP90437.
22. González-Salvatierra S, García-Martín A, García-Fontana B, et al. Bone proteins are associated with cardiovascular risk according to the SCORE2-Diabetes algorithm. Cardiovasc Diabetol, 2024, 23(1): 311.
23. 譚艷飛, 譚艷美, 梅瑯. 血清骨硬化蛋白、內皮細胞特異性分子 1 與 2 型糖尿病亞臨床動脈粥樣硬化的關系. 中國動脈硬化雜志, 2022, 30(5): 410-415.
24. Liu H, Guo Y, Zhu R, et al. Fructus Ligustri Lucidi preserves bone quality through induction of canonical Wnt/β‐catenin signaling pathway in ovariectomized rats. Phytother Res, 2021, 35(1): 424-441.
25. Bovijn J, Krebs K, Chen CY, et al. Evaluating the cardiovascular safety of sclerostin inhibition using evidence from meta‐analysis of clinical trials and human genetics. Sci Transl Med, 2020, 12(549): eaay6570.
26. Zhao B, Chen A, Wang H, et al. The relationship between sclerostin and carotid artery atherosclerosis in patients with stage 3-5 chronic kidney disease. Int Urol Nephrol, 2020, 52(7): 1329-1336.
27. 周琳, 李世軍. 冠心病與骨質疏松癥共病的機制與治療進展. 中國臨床保健雜志, 2023, 26(5): 712-717.
28. Tsourdi E, Rachner TD, Hofbauer LC. Romosozumab versus alendronate and fracture risk in women with osteoporosis. N Engl J Med, 2018, 378(2): 195.
29. Holdsworth G, Staley JR, Hall P, et al. Sclerostin downregulation globally by naturally occurring genetic variants, or locally in atherosclerotic plaques, does not associate with cardiovascular events in humans. J Bone Miner Res, 2021, 36(7): 1326-1339.
30. Golledge J, Thanigaimani S. Role of sclerostin in cardiovascular disease. Arterioscler Thromb Vasc Biol, 2022, 42(7): e187-e202.
31. Movérare-Skrtic S, Voelkl J, Nilsson KH, et al. Ohlsson C. B4GALNT3 regulates glycosylation of sclerostin and bone mass. EBioMedicine, 2023, 91: 104546.

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