Toll-Like Receptor 2 可减轻血管紧张素 II 诱导的载脂蛋白E-/-小鼠腹主动脉瘤的形成和发展。

IF 1.8 4区医学 Q3 PERIPHERAL VASCULAR DISEASE Journal of Vascular Research Pub Date : 2024-10-28 DOI:10.1159/000541651

Yali Zhang, Jessamyn Bagley, Ho-Jin Park, Xuehong Cao, Elena Maganto-Garcia, Andrew Lichtman, Debbie Beasley, Jonas B Galper

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引用次数: 0

摘要

导言：我们已经证实，Toll样受体（TLR）4参与了血管紧张素II（AngII）介导的腹主动脉瘤（AAA）形成的发病机制。在此，我们研究了 TLR2 在 AAA 形成中的作用：雄性载脂蛋白E-/-和载脂蛋白E-/-TLR2-/-小鼠接受AngII治疗。给小鼠注射 TLR2 激动剂 Pam3CSK4。测定AAA的发病率和严重程度。对 MCP-1、MCP-5、RANTES、CXCL10、CCR5 和 CXCR3 进行了分析。流式细胞术检测了主动脉中的 M1 和 M2 巨噬细胞：这些研究表明，TLR2-/-小鼠 AAA 的形成增加，而 Pam3CSK4 则减少。Pam3CSK4 可降低 M1/M2 的比例以及 RANTES、CXCL10、CCR5 和 CXCR3 的水平。此外，Pam3CSK4 在 AngII 后一周的治疗可延缓 AAA 的进展：这些数据表明，TLR2 信号对 AAA 有保护作用，同时降低了 M1 与 M2 巨噬细胞的比例以及趋化因子及其受体的表达。此外，在使用 Pam3CSK4 治疗 AngII 后，病变进展明显延缓。鉴于大多数 AAA 患者都是在疾病晚期才被发现，这些研究结果表明，TLR2 刺激可能在延缓疾病进展方面发挥治疗作用。

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Toll-Like Receptor 2 Attenuates the Formation and Progression of Angiotensin II-Induced Abdominal Aortic Aneurysm in ApoE-/- Mice.

Introduction: We demonstrated Toll-like receptor (TLR) 4 in the pathogenesis of angiotensin II (AngII)-mediated abdominal aortic aneurysm (AAA) formation. Here, we study TLR2 in the AAA formation.

Methods: Male ApoE-/- and ApoE-/-TLR2-/- mice were treated with AngII. Mice were injected with the TLR2 agonist Pam3CSK4. The incidence and severity of AAA were determined. MCP-1, MCP-5, RANTES, CXCL10, CCR5, and CXCR3 were analyzed. M1 and M2 macrophages in the aorta were detected by flow cytometry.

Results: These studies demonstrated an increase in AAA formation in TLR2-/- mice and a decrease by Pam3CSK4. Pam3CSK4 decreased the ratio of M1/M2 and the levels of RANTES, CXCL10, CCR5, and CXCR3. Furthermore, Pam3CSK4 treatment 1 week following AngII retarded the progression of AAA.

Conclusion: These data demonstrated a protective effect of TLR2 signaling on AAA in association with a decrease in the ratio of M1 to M2 macrophages and the expression of chemokines and their receptors. Furthermore, the treatment of Pam3CSK4 after AngII demonstrated a marked retardation of lesion progression. Given the fact that most AAA patients are detected late in the disease process, these findings suggest that TLR2 stimulation may play a therapeutic role in retarding disease progression.

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来源期刊

Journal of Vascular Research 医学-生理学

CiteScore

3.40

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： The ''Journal of Vascular Research'' publishes original articles and reviews of scientific excellence in vascular and microvascular biology, physiology and pathophysiology. The scope of the journal covers a broad spectrum of vascular and lymphatic research, including vascular structure, vascular function, haemodynamics, mechanics, cell signalling, intercellular communication, growth and differentiation. JVR''s ''Vascular Update'' series regularly presents state-of-the-art reviews on hot topics in vascular biology. Manuscript processing times are, consistent with stringent review, kept as short as possible due to electronic submission. All articles are published online first, ensuring rapid publication. The ''Journal of Vascular Research'' is the official journal of the European Society for Microcirculation. A biennial prize is awarded to the authors of the best paper published in the journal over the previous two years, thus encouraging young scientists working in the exciting field of vascular biology to publish their findings.