1752-P: Investigating Cardiovascular Protective Molecular Mechanisms Associated with Liraglutide

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Introduction and Objective: Cardiovascular diseases and obesity pose significant global health challenges. Liraglutide, a GLP-1 receptor agonist, has demonstrated potential synergistic effects in weight management and promoting vascular health. This study aims to investigate the molecular mechanisms involved in vascular smooth muscle cells (VSMCs) and human umbilical vein endothelial cells (HUVECs) proliferation on treatment with GLP-1RA. Methods: Mechanistic studies were conducted on HUVECs and VSMCs treated with high glucose and liraglutide. RNA and proteins were extracted 48 hours post-treatment. Proliferative pathways were selected for further investigation. Gene and protein expression changes were analysed using qPCR and Western Blot, respectively. Cytotoxicity of each treatment was determined using cell counting kit 8. Statistical analyses were performed using one-way ANOVA combined with a non-parametric approach and Dunn's post-hoc multiple comparisons test. Results: Literature screening showed proliferation in HUVEC and VSMCs depends on Akt, MAPK/Erk, VEGF and MTOR pathways. The gene expression of AKT1(mTOR), PLA2G4A (MAPK and VEGF pathway), was decreased in the HUVECs and VSMC treated with liraglutide (p<0.05). Whilst the gene expression of PTPN3 (MAPK pathway) was increased in HUVECs and decreased in VSMC treated with liraglutide (p<0.05). Cell cytotoxicity assay results show that the cell death is lower in VSMC treated with liraglutide compared to the high glucose and control groups. Conclusion: This study demonstrates that the proliferation rate of VSMC and HUVECs is lower in the presence of liraglutide. Thereby indicting that the cardiovascular protective effect of liraglutide. These findings highlight GLP1RA s as promising therapeutic avenues for advancing cardiovascular and metabolic health treatment. Disclosure A. Duggirala: None. A. Wisniewska: None. A. Murphy: None. G. Tripathi: None.

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