<p>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.</p> Graphical Abstract <p></p>

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Class III Phosphatidylinositol-3 Kinase/Vacuolar Protein Sorting 34 in Cardiovascular Health and Disease

  • Yuanjun Shen,
  • Jason P. Gleghorn

摘要

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.

Graphical Abstract