Shen Yuanjun, Gleghorn Jason P
Departments of Biomedical Engineering, University of Delaware, Newark, DE, USA.
School of Pharmacy and Pharmceutical Sciences, Binghamton University, Johnson City, NY, USA.
J Cardiovasc Transl Res. 2025 Apr;18(2):392-407. doi: 10.1007/s12265-024-10581-z. Epub 2025 Jan 16.
Phosphatidylinositol-3 kinases (PI3Ks) play a critical role in maintaining cardiovascular health and the development of cardiovascular diseases (CVDs). Specifically, vacuolar Protein Sorting 34 (VPS34) or PIK3C3, the only member of Class III PI3K, plays an important role in CVD progression. The main function of VPS34 is inducing the production of phosphatidylinositol 3-phosphate, which, together with other essential structural and regulatory proteins in forming VPS34 complexes, further regulates the mammalian target of rapamycin activation, autophagy, and endocytosis. VPS34 is found to have crucial functions in the cardiovascular system, including dictating the proliferation and survival of vascular smooth muscle cells and cardiomyocytes and the formation of thrombosis. This review aims to summarize our current knowledge and recent advances in understanding the function and regulation of VPS34 in cardiovascular health and disease. We also discuss the current development of VPS34 inhibitors and their potential to treat CVDs.
磷脂酰肌醇-3激酶（PI3Ks）在维持心血管健康及心血管疾病（CVDs）的发展过程中发挥着关键作用。具体而言，III类PI3K的唯一成员——液泡蛋白分选34（VPS34）或PIK3C3，在CVD进展中起重要作用。VPS34的主要功能是诱导磷脂酰肌醇3-磷酸的产生，其与其他重要的结构和调节蛋白一起形成VPS34复合物，进一步调节雷帕霉素哺乳动物靶点的激活、自噬和内吞作用。研究发现VPS34在心血管系统中具有关键功能，包括决定血管平滑肌细胞和心肌细胞的增殖与存活以及血栓形成。本综述旨在总结我们目前对VPS34在心血管健康和疾病中的功能及调节的认识和最新进展。我们还讨论了VPS34抑制剂的当前研发情况及其治疗CVDs的潜力。
