Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK.
Cells. 2022 Aug 11;11(16):2494. doi: 10.3390/cells11162494.
Vascular diseases account for a significant number of deaths worldwide, with cardiovascular diseases remaining the leading cause of mortality. This ongoing, ever-increasing burden has made the need for an effective treatment strategy a global priority. Recent advances in regenerative medicine, largely the derivation and use of induced pluripotent stem cell (iPSC) technologies as disease models, have provided powerful tools to study the different cell types that comprise the vascular system, allowing for a greater understanding of the molecular mechanisms behind vascular health. iPSC disease models consequently offer an exciting strategy to deepen our understanding of disease as well as develop new therapeutic avenues with clinical translation. Both transcriptional and post-transcriptional mechanisms are widely accepted to have fundamental roles in orchestrating responses to vascular damage. Recently, iPSC technologies have increased our understanding of RNA-binding proteins (RBPs) in controlling gene expression and cellular functions, providing an insight into the onset and progression of vascular dysfunction. Revelations of such roles within vascular disease states have therefore allowed for a greater clarification of disease mechanisms, aiding the development of novel therapeutic interventions. Here, we discuss newly discovered roles of RBPs within the cardio-vasculature aided by iPSC technologies, as well as examine their therapeutic potential, with a particular focus on the Quaking family of isoforms.
血管疾病在全球范围内造成了大量的死亡，心血管疾病仍然是主要的死亡原因。这种持续不断、日益增加的负担使得需要一种有效的治疗策略成为全球的优先事项。再生医学的最新进展，主要是诱导多能干细胞（iPSC）技术作为疾病模型的衍生和应用，为研究构成血管系统的不同细胞类型提供了强大的工具，使我们能够更好地了解血管健康背后的分子机制。因此，iPSC 疾病模型为我们提供了一种令人兴奋的策略，可以加深我们对疾病的理解，并开发具有临床转化的新治疗途径。转录和转录后机制都被广泛认为在协调对血管损伤的反应中起着基本作用。最近，iPSC 技术提高了我们对 RNA 结合蛋白（RBP）在控制基因表达和细胞功能中的作用的理解，深入了解了血管功能障碍的发生和进展。因此，在血管疾病状态下发现这些作用，使我们能够更好地阐明疾病机制，从而为新的治疗干预措施的发展提供帮助。在这里，我们讨论了 iPSC 技术辅助下心血管系统中 RBP 的新发现作用，并研究了它们的治疗潜力，特别关注 Quaking 家族同工型。
