Department of Geriatrics, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, Guangdong, China.
Department of Hypertension and Vascular Disease, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.
Oxid Med Cell Longev. 2021 Jul 18;2021:5561272. doi: 10.1155/2021/5561272. eCollection 2021.
The disruption of endothelial homeostasis is the hallmark of coronary artery disease (CAD) and psychological disorders such as anxiety/depression. Xinkeshu (XKS), a traditional Chinese patent medicine, plays an essential role in CAD and psychological condition; however, the mechanisms underlying the effects of XKS on the endothelial function and endogenous endothelium-repair capacity in CAD patients with anxiety/depression remain elusive. In this study, endothelial function and endothelial progenitor cell- (EPC-) mediated reendothelialization capacity were compared among age-matched healthy subjects, CAD patients with or without anxiety/depression. Besides, CAD patients with anxiety/depression received 1-month XKS treatment. Anxiety/depression symptoms were evaluated by Generalized Anxiety Disorder 7-item (GAD-7)/Patient Health Questionnaire-9 (PHQ-9) score, endothelial function was tested by flow mediated dilation (FMD) measurement, and EPC-mediated reendothelialization capacity was evaluated by a carotid artery injury model in nude mouse ( = 6) with the injection of XKS-incubated EPCs from CAD patients with anxiety/depression. The results showed that FMD and EPC-mediated reendothelialization capacity of CAD patients with anxiety/depression were compromised compared to healthy subjects and CAD patients without anxiety/depression. After 1 month of XKS treatment, FMD increased from 4.29 ± 1.65 to 4.87 ± 1.58% ( < 0.05) in CAD patients with anxiety/depression, whereas it remained unchanged in the controls. Moreover, XKS decreased GAD-7 and PHQ-9 scores. Meanwhile, incubating XKS enhanced reendothelialization capacity and apoptosis of EPCs from CAD patients with anxiety/depression, which was associated with the upregulation of CXC-chemokine receptor 7 (CXCR7) and inhibition of phosphorylation of p38 signaling. CXCR7 knockdown abolished the beneficial effects of XKS, which was rescued by p38 inhibitor SB203580. Our data demonstrate for the first time that XKS improves endothelial function and enhances EPC-mediated reendothelialization through CXCR7/p38/cleaved casepase-3 signaling and provides novel insight into the detailed mechanism of XKS in maintaining endothelial homeostasis in CAD patients with anxiety/depression.
内皮稳态的破坏是冠心病 (CAD) 和焦虑/抑郁等心理障碍的标志。心可舒（XKS）是一种传统的中药，在 CAD 和心理状态中起着重要作用；然而，XKS 对 CAD 伴焦虑/抑郁患者内皮功能和内源性内皮修复能力的影响机制仍不清楚。在这项研究中，比较了年龄匹配的健康受试者、伴或不伴焦虑/抑郁的 CAD 患者之间的内皮功能和内皮祖细胞（EPC）介导的再内皮化能力。此外，CAD 伴焦虑/抑郁的患者接受了 1 个月的 XKS 治疗。焦虑/抑郁症状通过广义焦虑障碍 7 项（GAD-7）/患者健康问卷-9（PHQ-9）评分评估，内皮功能通过血流介导的扩张（FMD）测量测试，EPC 介导的再内皮化能力通过注射来自 CAD 伴焦虑/抑郁患者的 XKS 孵育的 EPC 的裸鼠颈动脉损伤模型评估（= 6）。结果表明，与健康受试者和 CAD 无焦虑/抑郁患者相比，CAD 伴焦虑/抑郁患者的 FMD 和 EPC 介导的再内皮化能力受损。在 XKS 治疗 1 个月后，CAD 伴焦虑/抑郁患者的 FMD 从 4.29±1.65%增加到 4.87±1.58%（<0.05），而对照组则没有变化。此外，XKS 降低了 GAD-7 和 PHQ-9 评分。同时，孵育 XKS 增强了 CAD 伴焦虑/抑郁患者 EPC 的再内皮化能力和凋亡，这与趋化因子受体 7（CXCR7）的上调和磷酸化 p38 信号的抑制有关。CXCR7 敲低消除了 XKS 的有益作用，而 p38 抑制剂 SB203580 则挽救了这种作用。我们的数据首次表明，XKS 通过 CXCR7/p38/cleaved casepase-3 信号改善内皮功能并增强 EPC 介导的再内皮化，为 XKS 维持 CAD 伴焦虑/抑郁患者内皮稳态的详细机制提供了新的见解。
