Yi Ming, Li Yan, Sun Jinghao, Si Jin, Liu Huirong, Li Jing
Department of Geriatrics, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, 100053, China.
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, China.
BMC Cardiovasc Disord. 2025 Jul 21;25(1):534. doi: 10.1186/s12872-025-05000-3.
The bone-specific protein osteocalcin (OCN) is an established marker of vascular calcification and vascular smooth muscle cell (VSMC) osteogenic trans-differentiation. Recent studies have revealed the regulatory function of externally administered OCN on atherosclerosis and vascular remodeling. However, the role of OCN in VSMCs involved in cell migration and neointima formation has not been clearly described.
Rat carotid-artery balloon-injury was performed to induce neointima formation. OCN expression was detected in injured carotid arteries by western blot and immunofluorescence staining. Rat primary cultured VSMCs were treated with tumor necrosis factor-α (TNF-α) and platelet-derived growth factor-BB (PDGF-BB). OCN overexpression was induced by virus infection. VSMC migration was detected by scratched wound-healing assay. The ratio of intima to media thickness and vascular cell adhesion molecule-1 (VCAM-1) expression were compared between wild type (WT) rat and OCN knockout (OCN-/-) rat after vascular injury. Blood pressure and vascular stiffness were detected between WT rat and OCN-/- rat by rat tail blood pressure test and small animal ultrasound.
OCN was significantly up-regulated in balloon-injured carotid arteries of rat and enhanced in VSMCs treated by the TNF-α and PDGF-BB. With OCN overexpression, VSMC proliferation and migration were simultaneously aggravated. OCN-/- rats maintained normal carotid artery architecture and function under physiological condition. After carotid artery injury, OCN-/- rats exhibited significantly reduced neointimal thickness and VCAM-1 expression of injured vessels compared to WT rats.
OCN participates in the pathological processes of vascular neointima formation and promotes inflammatory response of VSMC to vascular injury, but deletion of OCN does not affect vascular integrity under physiological condition, suggesting that OCN may provide new insights into the mechanism of intima hyperplasia.
骨特异性蛋白骨钙素（OCN）是已确定的血管钙化和血管平滑肌细胞（VSMC）成骨转分化标志物。最近的研究揭示了外源性给予OCN对动脉粥样硬化和血管重塑的调节作用。然而，OCN在参与细胞迁移和新生内膜形成的VSMC中的作用尚未明确描述。
进行大鼠颈动脉球囊损伤以诱导新生内膜形成。通过蛋白质免疫印迹法和免疫荧光染色检测损伤颈动脉中OCN的表达。用肿瘤坏死因子-α（TNF-α）和血小板衍生生长因子-BB（PDGF-BB）处理大鼠原代培养的VSMC。通过病毒感染诱导OCN过表达。通过划痕伤口愈合试验检测VSMC迁移。比较野生型（WT）大鼠和OCN基因敲除（OCN-/-）大鼠血管损伤后的内膜与中膜厚度比值以及血管细胞黏附分子-1（VCAM-1）表达。通过大鼠尾动脉血压测试和小动物超声检测WT大鼠和OCN-/-大鼠之间的血压和血管硬度。
OCN在大鼠球囊损伤的颈动脉中显著上调，并在TNF-α和PDGF-BB处理的VSMC中增强。随着OCN过表达，VSMC增殖和迁移同时加剧。OCN-/-大鼠在生理条件下维持正常的颈动脉结构和功能。颈动脉损伤后，与WT大鼠相比，OCN-/-大鼠损伤血管的新生内膜厚度和VCAM-1表达显著降低。
OCN参与血管新生内膜形成的病理过程，并促进VSMC对血管损伤的炎症反应，但在生理条件下敲除OCN不影响血管完整性，提示OCN可能为内膜增生机制提供新的见解。
