Department of Hypertension, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
Department of Hypertension Research, Beijing Anzhen Hospital, Capital Medical University and Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing, China.
Cell Biol Int. 2021 May;45(5):989-1000. doi: 10.1002/cbin.11542. Epub 2021 Jan 15.
C1q-tumor necrosis factor-related protein-9 (CTRP9) is an important adipocytokine that is closely associated with cardiovascular disease. This study aimed to detect CTRP9 expression in hypertensive patients and mice and to analyze its effects on hypertension-related atherogenesis. First, circulating CTRP9 levels were detected in both nonhypertensive subjects and hypertensive patients. The results showed that plasma CTRP9 levels were increased in hypertension patients compared with control subjects and gradually elevated in the Grade I, Grade II, and Grade III groups. While nondipper state did not affect CTRP9 expression in hypertension patients. Hypertension patients with carotid atherosclerotic plaque (CAP) exhibited higher CTRP9 levels and the high CTRP9 group exhibited significantly higher CAP morbidity, CTRP9 levels were positively correlated with the occurrence of CAP. Then, effects of CTRP9 on angiotensin II (Ang II)-induced endothelial dysfunction were analyzed in vitro, and the results exhibited that treatment with Ang II significantly increased CTRP9 mRNA expression in endothelial cells (ECs), and downregulation of CTRP9 expression aggravated Ang II-induced endothelial dysfunction in ECs. Mice were infused with Ang II, and CTRP9 was also increased in Ang II-infused mice and mainly secreted by ECs. In Ang II-infused ApoE mice, treatment with recombinant CTRP9 significantly reduced atherosclerotic area and alleviated endothelial dysfunction. In conclusion, our results may found that CTRP9 delayed the progression of hypertension-related arteriosclerosis by alleviating endothelial dysfunction.
C1q-肿瘤坏死因子相关蛋白 9(CTRP9)是一种重要的脂肪细胞因子,与心血管疾病密切相关。本研究旨在检测高血压患者和小鼠中 CTRP9 的表达,并分析其对高血压相关动脉粥样硬化形成的影响。首先,检测了非高血压患者和高血压患者循环中 CTRP9 的水平。结果表明,与对照组相比,高血压患者的血浆 CTRP9 水平升高,且在 I 级、II 级和 III 级组中逐渐升高。而非杓型高血压患者的 CTRP9 表达不受影响。患有颈动脉粥样硬化斑块(CAP)的高血压患者表现出更高的 CTRP9 水平,且高 CTRP9 组的 CAP 发病率显著更高,CTRP9 水平与 CAP 的发生呈正相关。然后,在体外分析了 CTRP9 对血管紧张素 II(Ang II)诱导的内皮功能障碍的影响,结果表明,Ang II 处理可显著增加内皮细胞(ECs)中 CTRP9 mRNA 的表达,下调 CTRP9 表达可加重 Ang II 诱导的 ECs 内皮功能障碍。用 Ang II 输注小鼠,Ang II 输注小鼠的 CTRP9 也增加,主要由 ECs 分泌。在 Ang II 输注 ApoE 小鼠中,用重组 CTRP9 治疗可显著减少动脉粥样硬化面积并减轻内皮功能障碍。综上所述,我们的结果可能表明,CTRP9 通过减轻内皮功能障碍来延缓高血压相关动脉粥样硬化的进展。