Sirtuin 1 (SIRT1) Content and Angiotensin II Receptor Type I (AT1) Expression in Human Umbilical Vein Endothelial Cells (HUVECs) in Response to Resveratrol: Pregnancy Induced Hypertension (PIH) vs Normotensive pregnancy (NTP)

Abstract

Oxidative stress and endothelial dysfunction within uteroplacental unit are inherent components initiating PIH. The normal decrease of vascular angiotensin II sensitivity is lost in PIH. The polyphenol stilbene compound resveratrol (3,5,4′‐trihydroxy‐trans‐stilbene) boosts endothelium‐dependent vasorelaxation enhancing endothelial nitrix oxide synthase (eNOS) production. In fact, resveratrol acts as a secondary regulator influencing more complex biological response that includes the sirtuin system. SIRT1 is highly expressed in endothelial cells and activated/modulated by resveratrol has been shown to target eNOS for deacetylation resulting in enhanced NO‐dependent vascular relaxation. Moreover, anti‐hypertensive effects of resveratrol may be a consequence of the angiotensin II receptor type I (AT1) modulation by SIRT1. The aim of the study was to examine comparatively the effect of resveratrol on SIRT level in HUVECs isolated after PIH vs. NTP. In addition, AT1 expressions were compared. HUVECs were isolated immediately after cesarean section delivery from PIH (N = 24) and NTP (N = 24) patients (group I and group II, respectively). The umbilical cord segments was subjected to collagenase digestion and the HUVECs were cultured in vitro under normoxia. After achieving the confluence, HUVECs were exposed to resveratrol (50, 100 and 250 μM) administered into the culture media in the respective subgroups A, B and C during the 7 day period. SIRT1 levels were determined in HUVECs culture lysates obtained in the days 1,3 and 7, using ELISA. After termination of the cultures AT1 were immunostained in formalin fixed and paraffin embedded sections. To estimate the mean expression of AT1, quantitative immunohostochemistry was applied. The initial AT1 expression was estimated in the respective controls. After 3 and 7 days of the culture, in both groups the mean SIRT1 levels were significantly (p < 0.05) higher in the subgroups B and C, compared to the initial levels at day 1. However, the mean SIRT1 levels in group I were 4.6‐fold and 2.4‐fold lower (the subgroups B and C, respectively) than observed in normotensive group II. The initial expression of AT1 was significantly higher in group I and amounted to 170% of the average value in the normotensive group II. The mean expression of AT1 was significantly (p < 0.05) downregulated in group I (the subgroups B and C), while in group II was nearly unaffected. These results may suggest potential beneficial effect of SIRT1 activation by resveratrol with regard to antihypertensive therapy in PIH.Support or Funding InformationWUM grant: 2M2‐W1‐17This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.