Department of Cardiovascular Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai, China ; Department of Renji-Med X Clinical Stem Cell Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai, China.
Department of Renji-Med X Clinical Stem Cell Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai, China.
Am J Transl Res. 2015 Feb 15;7(2):232-41. eCollection 2015.
Thoracic aortic aneurysm (TAA) is progressive fatal aortic pathological dilation. However, the underlying molecular mechanisms are still largely unknown. Evidences suggest that endothelial cells and renin-angiotensin system may participate in the pathogenesis of TAA. This study aimed to investigate whether angiotensin II type 2 receptor (AT2) positive cells are involved in TAA formation. The mRNA level of AT2 is dramatically elevated in TAA compared with in controls. CD4(+)AT2(+) cells increased in both aortic wall and circulation of TAA patients. The levels of IL-1β and IL-17B in CD4(+)AT2(+) cells were lower than those in CD4(+)AT2(-) cells. When compared with endothelial cells (ECs) cultured alone, CD4(+)AT2(+) cells showed an inhibitory effect on proliferation and MMP2 expression in ECs, but CD4(+)AT2(-) cells promoted proliferation and MMP2 expression in ECs. Both CD4(+)AT2(+) and CD4(+)AT2(-) cells suppressed apoptosis of ECs. In conclusion, we have identified a novel population of CD4(+)AT2(+) T lymphocytes that show protective effect in TAA through inhibition of growth, apoptosis, and MMP2 expression in ECs.
胸主动脉瘤（TAA）是一种进行性致命的主动脉病理性扩张。然而，其潜在的分子机制在很大程度上仍不清楚。有证据表明，内皮细胞和肾素-血管紧张素系统可能参与 TAA 的发病机制。本研究旨在探讨血管紧张素 II 型受体（AT2）阳性细胞是否参与 TAA 的形成。与对照组相比，TAA 中的 AT2mRNA 水平显著升高。TAA 患者的主动脉壁和循环中 CD4+AT2+细胞增加。CD4+AT2+细胞中的白细胞介素 1β（IL-1β）和白细胞介素 17B（IL-17B）水平低于 CD4+AT2-细胞。与单独培养的内皮细胞（ECs）相比，CD4+AT2+细胞对 ECs 的增殖和 MMP2 表达具有抑制作用，但 CD4+AT2-细胞促进 ECs 的增殖和 MMP2 表达。CD4+AT2+和 CD4+AT2-细胞均抑制 ECs 的凋亡。总之，我们鉴定了一种新型的 CD4+AT2+T 淋巴细胞亚群，通过抑制 ECs 的生长、凋亡和 MMP2 表达，在 TAA 中发挥保护作用。
