Hydroxytyrosol Prevents Vascular Intimal Hyperplasia in Vascular in Vitro and ex vivo Saphenous Vein Ring Culture Models by Modulating the Akt and Nrf2/HO-1 Pathways.

Hydroxytyrosol Prevents Vascular Intimal Hyperplasia in Vascular in Vitro and ex vivo Saphenous Vein Ring Culture Models by Modulating the Akt and Nrf2/HO-1 Pathways. | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 28 July 2025 V1 Latest version Share on Hydroxytyrosol Prevents Vascular Intimal Hyperplasia in Vascular in Vitro and ex vivo Saphenous Vein Ring Culture Models by Modulating the Akt and Nrf2/HO-1 Pathways. Authors : Ubashini Vijakumaran , Muhammad Dain Yazid , Eva Jover , Nur Ayub Md Ali , Hairulfaizi Haron , Muhammad Ishamuddin Ismail , Mohd Ramzisham Abdul Rahman , and Nadiah Sulaiman 0000-0002-3965-1850 [email protected] Authors Info & Affiliations https://doi.org/10.22541/au.175370787.72074962/v1 182 views 72 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Background : Venous intimal hyperplasia (VIH) contributes to luminal vascular thickening, which compromises the long-term patency of coronary artery bypass grafting (CABG) grafts and negatively impacts the outcomes of percutaneous coronary intervention. Antiproliferative drugs that impair endothelial cell (EC) function can exacerbate VIH. Additionally, endothelial dysfunction leads to an imbalance in reactive oxygen species, further inducing excessive vascular remodelling. Hydroxytyrosol (HT), an olive oil derivative, has been proved to exert antioxidant, anti-inflammatory, and antiproliferative effects. We hypothesize that HT could inhibit smooth muscle cell (SMC) proliferation without compromising EC homeostasis, thus emerging as an adjuvant solution to prevent intimal hyperplasia in patients undergoing CABG. Methods & Results : Dose-response experiments of HT were conducted in vitro on ECs and PDGF-BB-stimulated SMCs. In vitro , HT at concentrations ranging from 40 μM to 320 μM, significantly inhibited PDGF-induced SMC proliferation, migration, and chemotaxis via downregulating Akt pathway. In contrast, HT concentrations below 50 μM preserved EC viability, proliferation, and migration. Additionally, HT activated the Nrf2/HO-1 antioxidant pathway in both cell types. Therefore, HT at 50uM was then tested in an ex vivo human saphenous vein (hSV) ring culture. In the ex vivo hSV model, a significant increase in cellular proliferation was observed from day 0 to day 21. HT treatment reduced intimal thickness by 44% and SMC proliferation by 53% (p=0.004), likely due to the inhibition of Akt and vimentin, along with the HO-1 activation. Conclusions : Our findings underscore the therapeutic potential of HT in preventing intimal hyperplasia as per its balanced effects on regulating the biological function of vessel resident cells. Further research is warranted to evaluate HT’s effect on reendothelialization, particularly using 3D disease models or animal studies. Supplementary Material File (main text.docx) Download 6.16 MB Information & Authors Information Version history V1 Version 1 28 July 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Authors Affiliations Ubashini Vijakumaran Universiti Kebangsaan Malaysia Fakulti Perubatan View all articles by this author Muhammad Dain Yazid Universiti Kebangsaan Malaysia Fakulti Perubatan View all articles by this author Eva Jover Instituto de Investigacion Sanitaria de Navarra View all articles by this author Nur Ayub Md Ali Hospital Canselor Tuanku Muhriz UKM View all articles by this author Hairulfaizi Haron Hospital Canselor Tuanku Muhriz UKM View all articles by this author Muhammad Ishamuddin Ismail Hospital Canselor Tuanku Muhriz UKM View all articles by this author Mohd Ramzisham Abdul Rahman Hospital Canselor Tuanku Muhriz UKM View all articles by this author Nadiah Sulaiman 0000-0002-3965-1850 [email protected] Universiti Kebangsaan Malaysia Fakulti Perubatan View all articles by this author Metrics & Citations Metrics Article Usage 182 views 72 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Ubashini Vijakumaran, Muhammad Dain Yazid, Eva Jover, et al. Hydroxytyrosol Prevents Vascular Intimal Hyperplasia in Vascular in Vitro and ex vivo Saphenous Vein Ring Culture Models by Modulating the Akt and Nrf2/HO-1 Pathways.. Authorea . 28 July 2025. DOI: https://doi.org/10.22541/au.175370787.72074962/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . 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