Class III Phosphatidylinositol-3 Kinase/Vacuolar Protein Sorting 34 in Cardiovascular Health and Disease
Yuanjun Shen1,2, Jason P Gleghorn3,4
1Departments of Biomedical Engineering, University of Delaware, Newark, DE, USA. yjshen@udel.edu.
Insights
Vacuolar protein sorting 34 (VPS34), a key enzyme in cardiovascular health, is crucial for cell survival and thrombosis. Understanding VPS34
Area of Science:
- Cardiovascular Biology
- Molecular Biology
- Biochemistry
Background:
- Phosphatidylinositol-3 kinases (PI3Ks) are vital in cardiovascular health and disease.
- Vacuolar protein sorting 34 (VPS34), the sole Class III PI3K, significantly impacts cardiovascular disease (CVD) progression.
- VPS34 regulates phosphatidylinositol 3-phosphate production, influencing mTOR signaling, autophagy, and endocytosis.
Purpose of the Study:
- To review current knowledge on VPS34 function and regulation in cardiovascular health and disease.
- To highlight recent advancements in understanding VPS34's role in the cardiovascular system.
- To discuss the therapeutic potential of VPS34 inhibitors for treating CVDs.
Main Methods:
- Literature review of scientific articles on VPS34 and cardiovascular systems.
- Analysis of VPS34's molecular functions, including its role in cell proliferation, survival, and thrombosis.
- Examination of current research on VPS34 inhibitors and their clinical applications.
Main Results:
- VPS34 is essential for vascular smooth muscle cell and cardiomyocyte proliferation and survival.
- VPS34 plays a critical role in the formation of thrombosis.
- VPS34's involvement in autophagy and endocytosis is crucial for cardiovascular homeostasis.
Conclusions:
- VPS34 is a key regulator of cardiovascular function and a potential therapeutic target for CVDs.
- Further research into VPS34 regulation and inhibition is warranted for developing novel CVD treatments.
- Targeting VPS34 may offer a promising strategy for managing cardiovascular diseases.
Abstract:
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.
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