In addition to serving as an incretin-based treatment of type 2 diabetes mellitus (T2DM), glucagon-like peptide 1 (GLP-1) can also reverse cardiovascular diseases caused by vascular remodelling. However, a detailed mechanism underlying how GLP-1 reverses vascular remodelling remains unclear. Here, Spontaneous hypertension rats (SHR) were used as an in vivo model of vascular remodelling. Treatment with a GLP-1 receptor (GLP-1R) agonist Liraglutide or dipeptidyl peptidase 4 (DPP4) inhibitor Alogliptin decreased systolic blood pressure (SBP), diastolic blood pressure (DBP), thickness of vascular wall, and overall collagen levels in SHR. In vitro vascular remodelling can be induced by exposing rat aortic smooth muscle cells (RASMC) to angiotensin II (Ang II); GLP-1 treatment attenuated AngII induction of RASMC proliferation, migration, and excessive extracellular matrix (ECM) degradation. Downregulation of matrix metalloproteinase 1 (MMP1) enhanced the inhibitory effects of GLP-1, and extracellular regulated protein kinase 1/2 (ERK1/2) and nuclear factor kappa-B (NF-κB) signalling participated in these processes. These results provide a new mechanistic understanding of key therapeutic strategies for the treatment of vascular remodelling-related diseases.

除了用作基于肠降血糖素的2型糖尿病（T2DM）治疗外，胰高血糖素样肽1（GLP-1）还可以逆转由血管重塑引起的心血管疾病。但是，尚不清楚GLP-1如何逆转血管重塑的详细机制。在这里，自发性高血压大鼠（SHR）被用作体内的血管重塑模型。使用GLP-1受体（GLP-1R）激动剂利拉鲁肽或二肽基肽酶4（DPP4）抑制剂阿格列汀治疗可降低收缩压（SBP），舒张压（DBP），血管壁厚度和SHR中的总体胶原蛋白水平。体外可以通过将大鼠主动脉平滑肌细胞（RASMC）暴露于血管紧张素II（Ang II）来诱导血管重塑；GLP-1处理减弱了AngII对RASMC增殖，迁移和过度的细胞外基质（ECM）降解的诱导。基质金属蛋白酶1（MMP1）的下调增强了GLP-1的抑制作用，而细胞外调节蛋白激酶1/2（ERK1 / 2）和核因子κB（NF-κB）信号传导参与了这些过程。这些结果为治疗血管重塑相关疾病的关键治疗策略提供了新的机制理解。