{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T13:37:17Z","timestamp":1780925837442,"version":"3.54.1"},"reference-count":64,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,5,16]],"date-time":"2023-05-16T00:00:00Z","timestamp":1684195200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Nanyang Technological University Internal","award":["702"],"award-info":[{"award-number":["702"]}]},{"name":"Nanyang Technological University Internal","award":["MOE2016703 T3-1-003"],"award-info":[{"award-number":["MOE2016703 T3-1-003"]}]},{"name":"AcRF Tier 3","award":["702"],"award-info":[{"award-number":["702"]}]},{"name":"AcRF Tier 3","award":["MOE2016703 T3-1-003"],"award-info":[{"award-number":["MOE2016703 T3-1-003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Hypoxia-induced vascular endothelial dysfunction (VED) is a significant contributor to several severe human diseases, including heart disease, stroke, dementia, and cancer. However, current treatment options for VED are limited due to the lack of understanding of the underlying disease mechanisms and therapeutic leads. We recently discovered a heat-stable microprotein in ginseng, called ginsentide TP1, that has been shown to reduce vascular dysfunction in cardiovascular disease models. In this study, we use a combination of functional assays and quantitative pulsed SILAC proteomics to identify new proteins synthesized in hypoxia and to show that ginsentide TP1 provides protection for human endothelial cells against hypoxia and ER stress. Consistent with the reported findings, we also found that hypoxia activates various pathways related to endothelium activation and monocyte adhesion, which in turn, impairs nitric oxide (NO) synthase activity, reduces the bioavailability of NO, and increases the production of reactive oxygen species that contribute to VED. Additionally, hypoxia triggers endoplasmic reticulum stress and initiates apoptotic signaling pathways associated with cardiovascular pathology. Treatment with ginsentide TP1 reduced surface adhesion molecule expression, prevented activation of the endothelium and leukocyte adhesion, restored protein hemostasis, and reduced ER stress to protect against hypoxia-induced cell death. Ginsentide TP1 also restored NO signaling and bioavailability, reduced oxidative stress, and protected endothelial cells from endothelium dysfunction. In conclusion, this study shows that the molecular pathogenesis of VED induced by hypoxia can be mitigated by treatment with ginsentide TP1, which could be one of the key bioactive compounds responsible for the \u201ccure-all\u201d effect of ginseng. This research may lead to the development of new therapies for cardiovascular disorders.<\/jats:p>","DOI":"10.3390\/cells12101401","type":"journal-article","created":{"date-parts":[[2023,5,17]],"date-time":"2023-05-17T01:52:41Z","timestamp":1684288361000},"page":"1401","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Ginsentide TP1 Protects Hypoxia-Induced Dysfunction and ER Stress-Linked Apoptosis"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2309-8771","authenticated-orcid":false,"given":"Bamaprasad","family":"Dutta","sequence":"first","affiliation":[{"name":"School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2220-8297","authenticated-orcid":false,"given":"Shining","family":"Loo","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore"},{"name":"Academy of Pharmacy, Xi\u2019an Jiaotong-Liverpool University, Suzhou 215123, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2155-6887","authenticated-orcid":false,"given":"Antony","family":"Kam","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore"},{"name":"Department of Biological Sciences, Xi\u2019an Jiaotong-Liverpool University, Suzhou 215123, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siu Kwan","family":"Sze","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore"},{"name":"Department of Health Sciences, Brock University, Niagara Region, St. Catharines, ON L2S 3A1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4433-198X","authenticated-orcid":false,"given":"James P.","family":"Tam","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.smrv.2014.06.003","article-title":"Does obstructive sleep apnea cause endothelial dysfunction? 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