Programmed cell death 5 suppresses AKT-mediated cytoprotection of endothelium

Seung Hyun Lee, Jaesung Seo, Soo Yeon Park, Mi Hyeon Jeong, Hyo Kyoung Choi, Chan Joo Lee, Mi Jeong Kim, Garam Guk, Soo Yeon Lee, Hyewon Park, Jae Wook Jeong, Chang Hoon Ha, Sungha Park, Ho Geun Yoon

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5 Citations (Scopus)

Abstract

Programmed cell death 5 (PDCD5) has been associated with human cancers as a regulator of cell death; however, the role of PDCD5 in the endothelium has not been revealed. Thus, we investigated whether PDCD5 regulates protein kinase B (PKB/AKT)-endothelial nitric oxide synthase (eNOS)–dependent signal transduction in the endothelium and affects atherosclerosis. Endothelial-specific PDCD5 knockout mice showed significantly reduced vascular remodeling compared with wild-type (WT) mice after partial carotid ligation. WT PDCD5 competitively inhibited interaction between histone deacetylase 3 (HDAC3) and AKT, but PDCD5L6R, an HDAC3-binding–deficient mutant, did not. Knockdown of PDCD5 accelerated HDAC3–AKT interaction, AKT and eNOS phosphorylation, and nitric oxide (NO) production in human umbilical vein endothelial cells. Moreover, we found that serum PDCD5 levels reflect endothelial NO production and are correlated with diabetes mellitus, high-density lipoprotein cholesterol, and coronary calcium in human samples obtained from the cardiovascular high-risk cohort. Therefore, we conclude that PDCD5 is associated with endothelial dysfunction and may be a novel therapeutic target in atherosclerosis.

Original languageEnglish
Pages (from-to)4672-4677
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number18
DOIs
Publication statusPublished - 2018 May 1

All Science Journal Classification (ASJC) codes

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    Lee, S. H., Seo, J., Park, S. Y., Jeong, M. H., Choi, H. K., Lee, C. J., Kim, M. J., Guk, G., Lee, S. Y., Park, H., Jeong, J. W., Ha, C. H., Park, S., & Yoon, H. G. (2018). Programmed cell death 5 suppresses AKT-mediated cytoprotection of endothelium. Proceedings of the National Academy of Sciences of the United States of America, 115(18), 4672-4677. https://doi.org/10.1073/pnas.1712918115