Walter-Brendel-Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München, 81377 Munich, Germany.
Medical Clinic I, Department of Cardiology, University Hospital, Ludwig Maximilian University, 81377 Munich, Germany.
Int J Mol Sci. 2023 Aug 16;24(16):12839. doi: 10.3390/ijms241612839.
Increasing evidence suggests that lymphocytes play distinct roles in inflammation-induced tissue remodeling and tissue damage. Arteriogenesis describes the growth of natural bypasses from pre-existing collateral arteries. This process compensates for the loss of artery function in occlusive arterial diseases. The role of innate immune cells is widely understood in the process of arteriogenesis, whereas the role of lymphocytes remains unclear and is the subject of the present study. To analyze the role of lymphocytes, we induced arteriogenesis in recombination activating gene-1 (Rag1) knockout (KO) mice by unilateral ligation of the femoral artery. The lack of functional lymphocytes in Rag1 KO mice resulted in reduced perfusion recovery as shown by laser Doppler imaging. Additionally, immunofluorescence staining revealed a reduced vascular cell proliferation along with a smaller inner luminal diameter in Rag1 KO mice. The perivascular macrophage polarization around the growing collateral arteries was shifted to more pro-inflammatory M1-like polarized macrophages. Together, these data suggest that lymphocytes are crucial for arteriogenesis by modulating perivascular macrophage polarization.
越来越多的证据表明，淋巴细胞在炎症诱导的组织重塑和组织损伤中发挥着不同的作用。动脉生成描述了从预先存在的侧支动脉生长出自然旁路的过程。这一过程补偿了闭塞性动脉疾病中动脉功能的丧失。先天免疫细胞在动脉生成过程中的作用已被广泛理解，而淋巴细胞的作用尚不清楚，这也是本研究的主题。为了分析淋巴细胞的作用，我们通过单侧结扎股动脉在重组激活基因-1（Rag1）敲除（KO）小鼠中诱导动脉生成。Rag1 KO 小鼠缺乏功能性淋巴细胞，导致激光多普勒成像显示灌注恢复减少。此外，免疫荧光染色显示 Rag1 KO 小鼠中的血管细胞增殖减少，内腔直径更小。围绕生长的侧支动脉的血管周巨噬细胞极化向更具炎症性的 M1 样极化巨噬细胞转移。总之，这些数据表明，淋巴细胞通过调节血管周巨噬细胞极化对动脉生成至关重要。
