MZe786 Rescues Cardiac Mitochondrial Activity in High sFlt-1 and Low HO-1 Environment

Abstract

Hypertensive disorder in pregnancy is a major cause of maternal and perinatal mortality worldwide. Women who have had preeclampsia are at three to four times higher risk in later life of developing high blood pressure and heart disease. Soluble Flt-1 (sFlt-1) is elevated in preeclampsia and may remain high postpartum in women with a history of preeclampsia. Heme oxygenase-1 (Hmox1/HO-1) exerts protective effects against oxidative stimuli and is compromised in the placenta of pregnant women with preeclampsia. We hypothesized that sFlt-1 inhibits cardiac mitochondrial activity in HO-1 deficient mice. HO-1 haplo-insufficient mice (Hmox1+/−) were injected with adenovirus encoding sFlt-1 (Ad-sFlt-1) or control virus (Ad-CMV). Subsequently, they were treated daily with either placebo or MZe786 for six days, when the heart tissue was harvested to assess cardiac mitochondrial activity. Here, we show that the loss of HO-1 disturbed cardiac mitochondrial respiration and reduced mitochondrial biogenesis. The overexpression of sFlt-1 resulted in the inhibition of the cardiac mitochondrial activity in Hmox1+/− mice. The present study demonstrates that the hydrogen sulfide (H2S) releasing molecule, MZe786, rescues mitochondrial activity by stimulating cardiac mitochondrial biogenesis and antioxidant defense in Hmox1−/− mice and in Hmox1+/− mice exposed to a high sFlt-1 environment.

Publication DOI: https://doi.org/10.3390/antiox9070598
Divisions: College of Health & Life Sciences > Aston Medical School
College of Health & Life Sciences > Aston Medical School > Translational Medicine Research Group (TMRG)
College of Health & Life Sciences > School of Biosciences
College of Health & Life Sciences > School of Biosciences > Cellular and Molecular Biomedicine
Additional Information: © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Uncontrolled Keywords: Antioxidants,Heme oxygenase-1,Hydrogen sulfide,Mitochondria,Preeclampsia,SFlt-1,Biochemistry,Physiology,Molecular Biology,Clinical Biochemistry,Cell Biology
Full Text Link:
Related URLs: https://www.mdp ... 76-3921/9/7/598 (Publisher URL)
http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2020-07-09
Accepted Date: 2020-07-06
Authors: Sanchez-aranguren, Lissette Carolina (ORCID Profile 0000-0002-4663-5752)
Rezai, Homira
Ahmad, Shakil (ORCID Profile 0000-0002-9294-0475)
Alzahrani, Faisal A.
Sparatore, Anna
Wang, Keqing (ORCID Profile 0000-0001-6239-6344)
Ahmed, Asif (ORCID Profile 0000-0002-8755-8546)

Download

[img]

Version: Published Version

License: Creative Commons Attribution

| Preview

Export / Share Citation


Statistics

Additional statistics for this record