10 Glutaredoxin-1 overexpression induces hypertensive pregnancy and maternal cardiac fibrosis. (22nd March 2023)

• Record Type: Journal Article
• Authors: Kerr, Jennifer; Lermant, Agathe; Murdoch, Colin E
• Is Part Of: Heart. Volume 109(2023)Supplement 2
• Page Start: A3
• Page End: A4
• Publication Date: 2023-03-22
• Subjects: Heart -- Diseases -- Treatment -- Periodicals; Cardiology -- Periodicals; 616.12
• DOI: 10.1136/heartjnl-SCF-2023.10
• Languages: English
• ISSNs: 1355-6037

Abstract

Abstract : Elevation of oxidative stress is explicitly linked to hypertensive pregnancies with high levels measurable in the maternal circulation. Hypertensive pregnancies lead to life-long risk of cardiac dysfunction, yet the underpinning molecular pathway are unknown. Oxidative stress modify proteins via oxidative post-translational modifications (ox-PTMs) which can regulate intracellular signalling by either potentiating or inhibiting protein activity. One of these, S-glutathionylation is a common oxPTM reversed by glutaredoxin (Glrx). We aimed to investigate the role of Glrx in a murine model of pregnancy combining physiological in vivo cardiac dynamics with histological assessment of maternal organs, to identify how perturbation of redox signalling can lead to cause pregnancy-induced cardiovascular complications. Mice overexpressing Glrx(Glrx-TG) and littermate controls (WT) underwent timed pregnancy. Left-ventricle (LV) pressure-volume (PV) loops was measured on day 18.5 by catheter inserted into LV. Pregnancy outcome and maternal organ pathology was conducted. At day 18.5 of pregnancy Glrx-TG mice had higher aortic blood pressure, with more incidents of fetal reabsorptions compared to WT. End-systolic pressure assessed from PV-loops showed a trend for increase in TG vs WT, although there was no overall effect on cardiac ejection fraction or stroke-volume. Interestingly, TG LV appeared to have higher contractility (End-systolic PV relationship). TG mice had an increase in cardiomyocyte size with no change in capillary density. Moreover, there was a significant increase in cardiac and renal fibrosis in Glrx-TG mothers. Further studies will be needed to identify the redox sensitive molecular pathways, that are altered by Glrx overexpression in the maternal cardiovascular system.