Science, Math & Technology, Singapore University of Technology & Design, Singapore 487372, Singapore; Genome Institute of Singapore (GIS), Agency for Science Technology and Research (A*STAR), 60 Biopolis Street, Genome, Singapore 138672, Singapore.
Science, Math & Technology, Singapore University of Technology & Design, Singapore 487372, Singapore; A*STAR Skin Research Labs (A*SRL), Skin Research Institute of Singapore (SRIS), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, #06-06 Immunos, Singapore 138648, Singapore.
Biochem Pharmacol. 2024 Nov;229:116507. doi: 10.1016/j.bcp.2024.116507. Epub 2024 Aug 23.
Diabetes mellitus is a metabolic disease with an escalating global prevalence. Despite the abundance and relative efficacies of current therapeutic approaches, they primarily focus on attaining the intended glycaemic targets, but patients ultimately still suffer from various diabetes-associated complications such as retinopathy, nephropathy, cardiomyopathy, and atherosclerosis. There is a need to explore innovative and effective diabetic treatment strategies that not only address the condition itself but also combat its complications. One promising option is the reproductive hormone relaxin, an endogenous ligand of the RXFP1 receptor. Relaxin is known to exert beneficial actions on the cardiovascular system through its vasoprotective, anti-inflammatory and anti-fibrotic effects. Nevertheless, the native relaxin peptide exhibits a short biological half-life, limiting its therapeutic potential. Recently, several relaxin mimetics and innovative delivery technologies have been developed to extend its biological half-life and efficacy. The current review provides a comprehensive landscape of the cardiovascular effects of relaxin, focusing on its potential therapeutic applications in managing complications associated with diabetes. The latest advancements in the development of relaxin mimetics and delivery methods for the treatment of cardiometabolic disorders are also discussed.
糖尿病是一种代谢性疾病，其全球患病率正在不断上升。尽管目前有大量且相对有效的治疗方法，但这些方法主要侧重于实现预期的血糖目标，但患者最终仍会遭受各种与糖尿病相关的并发症，如视网膜病变、肾病、心肌病和动脉粥样硬化。因此，需要探索创新且有效的糖尿病治疗策略，不仅要解决疾病本身，还要应对其并发症。一种有前途的选择是生殖激素松弛素，它是 RXFP1 受体的内源性配体。松弛素通过其血管保护、抗炎和抗纤维化作用对心血管系统发挥有益作用。然而，天然松弛素肽的生物半衰期较短，限制了其治疗潜力。最近，已经开发出几种松弛素类似物和创新的输送技术来延长其生物半衰期和功效。本综述全面介绍了松弛素的心血管作用，重点讨论了其在治疗与糖尿病相关的并发症方面的潜在治疗应用。还讨论了松弛素类似物的最新进展和用于治疗心脏代谢疾病的输送方法。
