TY - JOUR
T1 - Role of Sclerostin in Cardiovascular System
AU - Zhang, Ning
AU - Wang, Luyao
AU - Li, Xiaofei
AU - Yang, Xin
AU - Tao, Xiaohui
AU - Jiang, Hewen
AU - Yu, Yuanyuan
AU - Liu, Jin
AU - Yu, Sifan
AU - Ma, Yuan
AU - Zhang, Baoting
AU - Zhang, Ge
N1 - This study was funded by the National Key R&D Program of China (2018YFA0800804), Hong Kong General Research Fund (HKBU 12102223, HKBU 12102524, HKBU 12100921, CUHK 14108322, CUHK 14109721, CUHK 14103121, CUHK 14103420), CUHK Direct Grant (4054714), the Young Scientists Fund of the National Natural Science Foundation of China (82300988), Hong Kong RGC Postdoctoral Fellowship Scheme (PDFS2122-2S03), Theme-based Research Scheme (T12-201-20R), Guangdong Basic and Applied Basic Research Foundation (2019B1515120089, 2020A1515110630, China), Interdisciplinary Research Clusters Matching Scheme of Hong Kong Baptist University (RC-IRCs/17-18/02, China), Guangdong-Hong Kong Technology Cooperation Funding Scheme (GHP/149/21GD, 2023A0505010015), and Hunan Provincial Key Areas R&D Plan-Key R&D Projects (2022WK2010).
PY - 2025/5/2
Y1 - 2025/5/2
N2 - Sclerostin, encoded by the SOST gene, is a novel bone anabolic target for bone diseases. Humanized anti-sclerostin antibody, romosozumab, was approved for treatment of postmenopausal osteoporosis by the US Food and Drug Administration (FDA), but with a black-box warning on cardiovascular risk. The clinical data regarding cardiovascular events from various pre-marketing and post-marketing studies of romosozumab were inconsistent. Overall, the cardiovascular risk of sclerostin inhibition could not be excluded. The restriction of romosozumab in patients with cardiovascular disease history would be necessary. Moreover, genome-wide association study (GWAS) analyses of SOST variants revealed inconsistent results of the association between SOST variations and cardiovascular diseases. Further research incorporating larger sample sizes and functional analyses are necessary. In analyses of serum/tissue sclerostin levels in patients with cardiovascular diseases, the results were controversial but indicated an association between sclerostin and the presence/severity/outcomes of cardiovascular diseases. Nonclinical studies in rodents indicated the inhibitory effect of sclerostin on inflammation, aortic aneurysm, atherosclerosis, and vascular calcification. Sclerostin loop3 participated in the inhibitory effect of sclerostin on bone formation, while the cardiovascular protective effect of sclerostin was independent of sclerostin loop3. Macrophagic sclerostin loop2–apolipoprotein E receptor 2 (ApoER2) interaction participated in the inhibitory effect of sclerostin on inflammation in vitro. Sclerostin in human aortic smooth muscle cells participated in the reduction in calcium deposition. The role of sclerostin in cardiovascular system deserves further investigation.
AB - Sclerostin, encoded by the SOST gene, is a novel bone anabolic target for bone diseases. Humanized anti-sclerostin antibody, romosozumab, was approved for treatment of postmenopausal osteoporosis by the US Food and Drug Administration (FDA), but with a black-box warning on cardiovascular risk. The clinical data regarding cardiovascular events from various pre-marketing and post-marketing studies of romosozumab were inconsistent. Overall, the cardiovascular risk of sclerostin inhibition could not be excluded. The restriction of romosozumab in patients with cardiovascular disease history would be necessary. Moreover, genome-wide association study (GWAS) analyses of SOST variants revealed inconsistent results of the association between SOST variations and cardiovascular diseases. Further research incorporating larger sample sizes and functional analyses are necessary. In analyses of serum/tissue sclerostin levels in patients with cardiovascular diseases, the results were controversial but indicated an association between sclerostin and the presence/severity/outcomes of cardiovascular diseases. Nonclinical studies in rodents indicated the inhibitory effect of sclerostin on inflammation, aortic aneurysm, atherosclerosis, and vascular calcification. Sclerostin loop3 participated in the inhibitory effect of sclerostin on bone formation, while the cardiovascular protective effect of sclerostin was independent of sclerostin loop3. Macrophagic sclerostin loop2–apolipoprotein E receptor 2 (ApoER2) interaction participated in the inhibitory effect of sclerostin on inflammation in vitro. Sclerostin in human aortic smooth muscle cells participated in the reduction in calcium deposition. The role of sclerostin in cardiovascular system deserves further investigation.
KW - cardiovascular system
KW - clinical data
KW - molecular understanding
KW - nonclinical data
KW - sclerostin
UR - http://www.scopus.com/inward/record.url?scp=105006663035&partnerID=8YFLogxK
U2 - 10.3390/ijms26104552
DO - 10.3390/ijms26104552
M3 - Journal article
SN - 1661-6596
VL - 26
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 10
M1 - 4552
ER -
