Defining the molecular mechanisms underpinning inflammatory regulation of the vasculature

定义支持脉管系统炎症调节的分子机制

• 批准号: 2884861
• 金额: --
• 依托单位: University of Aberdeen
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2884861
• 关键词: Defining; molecular; mechanisms; underpinning; inflammatory

This project will investigate the utility of novel anti-inflammatory compounds in the regulation of the cardiovascular system. Cardiovascular disease (CVD) remains the leading cause of death worldwide, number 1 in Scotland and it is now widely accepted that chronic inflammation is a major driver of disease progression. Previous attempts to inhibit the inflammatory response have resulted in an increased susceptibility to infection. Hence, understanding the molecular mechanisms underlying inflammation regulation and its contribution to CVD is therefore critical to well-being and for the development of more effective therapies.Specifically, this study will investigate the molecular processes engaged by activation of the 'highly druggable' formyl peptide receptor 2 (FPR2). Research has shown FPR2 is essential in controlling the switch from pro-inflammation to pro-resolution signalling to enable tissue healing and, as such, has been proposed as a potential candidate for the development of novel therapeutics targeting chronic inflammation. Excitingly, our recent work has uncovered new insight, indicating endocytic trafficking of FPR2 is critical for the resolution of inflammation. We have discovered disruption of FPR2 trafficking increased cellular apoptosis; reported as a key requirement for resolution. This finding provides a novel molecular target for understanding inflammation and the development of therapeutics. Finally, the consequences of FPR2 stimulation is ligand-specific and can determine whether signalling is beneficial or detrimental. However, the molecular mechanisms defining these opposing physiological outcomes are poorly understood. This study will elucidate these processes.

该项目将研究新型抗炎化合物在调节心血管系统中的效用。心血管疾病 (CVD) 仍然是全球主要死亡原因，在苏格兰排名第一，现在人们普遍认为慢性炎症是疾病进展的主要驱动因素。先前抑制炎症反应的尝试导致感染易感性增加。因此，了解炎症调节的分子机制及其对 CVD 的贡献对于健康和开发更有效的疗法至关重要。具体来说，这项研究将研究“高度可成药”甲酰基肽激活所涉及的分子过程。受体 2 (FPR2)。研究表明，FPR2 对于控制从促炎症信号转为促消退信号传导以实现组织愈合至关重要，因此，FPR2 已被提议作为开发针对慢性炎症的新型疗法的潜在候选者。令人兴奋的是，我们最近的工作发现了新的见解，表明 FPR2 的内吞运输对于炎症的解决至关重要。我们发现 FPR2 运输的破坏会增加细胞凋亡；报告为解决方案的关键要求。这一发现为理解炎症和治疗方法的开发提供了一个新的分子靶点。最后，FPR2 刺激的后果是配体特异性的，可以确定信号传导是有益还是有害。然而，人们对定义这些相反的生理结果的分子机制知之甚少。这项研究将阐明这些过程。