An alternative renin isoform is cardioprotective by modulating mitochondrial metabolism. Issue 12 (24th September 2018)

• Record Type: Journal Article
• Authors: Wanka, Heike; Lutze, Philipp; Staar, Doreen; Grunow, Bianka; Peters, Barbara S.; Peters, Jörg
• Is Part Of: Journal of cellular and molecular medicine. Volume 22:Issue 12(2018)
• Page Start: 5991
• Page End: 6001
• Publication Date: 2018-09-24
• Subjects: aerobic glycolysis -- cytosolic renin -- exon(1A‐9)renin -- exon‐b renin -- H9c2 cells -- heart -- mitochondrial spare capacity -- Warburg effect; Cytology; Medicine; Molecular Biology; Cytologie -- Périodiques; Médecine -- Périodiques; Biologie moléculaire -- Périodiques; Cytology -- Periodicals; Medicine -- Periodicals; Molecular biology -- Periodicals; 611.01805
• DOI: 10.1111/jcmm.13872
• Languages: English
• ISSNs: 1582-1838

Abstract

Abstract: The renin‐angiotensin system promotes oxidative stress, apoptosis, necrosis, fibrosis, and thus heart failure. Secretory renin plays a central role in these processes, initiating the generation of angiotensins. Nevertheless, alternative renin transcripts exist, which code for a cytosolically localized renin isoform (cyto‐renin) that is cardioprotective. We tested the hypothesis that the protective effects are associated with a beneficial switch of metabolic and mitochondrial functions. To assess H9c2 cell mitochondrial parameters, we used the Seahorse XF analyser. Cardiac H9c2 cells overexpressing cyto‐renin exhibited enhanced nonmitochondrial oxygen consumption, lactate accumulation, and LDH activity, reflecting a switch to more aerobic glycolysis known as Warburg effect. Additionally, mitochondrial spare capacity and cell respiratory control ratio were enhanced, indicating an increased potential to tolerate stress conditions. Renin knockdown induced opposite effects on mitochondrial functions without influencing metabolic parameters. Thus, the protective effects of cyto‐renin are associated with an altered bioenergetic profile and an enhanced stress tolerance, which are favourable under ischaemic conditions. Therefore, cyto‐renin is a promising new target for the prevention of ischaemia‐induced myocardial damage.