7 The effect of glutaredoxin-1 in western diet induced cardiovascular pathophysiology: an assessment of sexual dimorphism in a mouse model. (22nd March 2023)

• Record Type: Journal Article
• Authors: Relan, Yahika; Kerr, Jennifer; McNeilly, Alison D; Murdoch, Colin E
• Is Part Of: Heart. Volume 109(2023)Supplement 2
• Page Start: A2
• Page End: A3
• Publication Date: 2023-03-22
• Subjects: Heart -- Diseases -- Treatment -- Periodicals; Cardiology -- Periodicals; 616.12
• DOI: 10.1136/heartjnl-SCF-2023.7
• Languages: English
• ISSNs: 1355-6037

Abstract

Abstract : Western diets, characterised by a high fat/high sucrose (HFHS) content, are associated with increased cardiac oxidative stress and cardiovascular diseases (CVDs). Increased post-translational modifications (oxPTM) like S-glutathionylation are correlated with the aetiology of CVD. Glutaredoxin-1 (Grx1) reverses S-glutathionylation and is overexpressed in CVDs. However, the role of Grx1 in HFHS-induced obesity and hypertension is unknown. This project aims to investigate potential sexual dimorphisms in the effect of HFHS diet-induced weight gain and cardiovascular pathophysiology in glutaredoxin-1 (Grx1Tg/+) overexpressing male and female mice. Grx1Tg/+ (TG) and wild-type (WT) littermates (Female and Male, 8-12 weeks) were exposed to a normal chow (NC) or HFHS diet for 10 weeks. Bodyweights were taken weekly and EchoMRI was conducted before and after diet exposure. After 10 weeks, LV pressure-volume loop and blood pressure were obtained by inserting a catheter into the LV under anaesthesia. In male and female WT mice, HFHS-diet increased bodyweight over 10-weeks. Interestingly, HFHS induced weight gain was attenuated in TG mice, accompanied with a decrease in% fat mass. HFHS-diet increased diastolic and mean blood pressure (BP). However, no significant increase in BP was observed in TG mice. In female TG mice, HFHS-diet reduced end diastolic volume stroke-volume and cardiac output compared to WT hearts. Heart-rates remained the same between all groups Overexpression of Grx1 attenuated weight-gain and% fat mass in male and female TG and hypertension in female TG. Additionally, it induced HFHS-diet induced cardiac remodelling in female TG.