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Article

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

1
Aston Medical Research Institute, Aston Medical School, Birmingham B4 7ET, UK
2
Mirzyme Therapeutics, Innovation Birmingham Campus, Faraday Wharf, Holt Street, Birmingham B7 4BB, UK
3
King Fahad Center for Medical Research, King Abdulaziz University, Jeddah 21589, Saudi Arabia
4
Department of Pharmaceutical Science, University of Milan, 20122 Milan, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Antioxidants 2020, 9(7), 598; https://doi.org/10.3390/antiox9070598
Received: 29 May 2020 / Revised: 2 July 2020 / Accepted: 6 July 2020 / Published: 9 July 2020
(This article belongs to the Special Issue Pharmacological and Clinical Significance of Heme Oxygenase-1)
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. View Full-Text
Keywords: heme oxygenase-1; sFlt-1; preeclampsia; mitochondria; antioxidants; hydrogen sulfide heme oxygenase-1; sFlt-1; preeclampsia; mitochondria; antioxidants; hydrogen sulfide
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MDPI and ACS Style

Sanchez-Aranguren, L.C.; Rezai, H.; Ahmad, S.; Alzahrani, F.A.; Sparatore, A.; Wang, K.; Ahmed, A. MZe786 Rescues Cardiac Mitochondrial Activity in High sFlt-1 and Low HO-1 Environment. Antioxidants 2020, 9, 598. https://doi.org/10.3390/antiox9070598

AMA Style

Sanchez-Aranguren LC, Rezai H, Ahmad S, Alzahrani FA, Sparatore A, Wang K, Ahmed A. MZe786 Rescues Cardiac Mitochondrial Activity in High sFlt-1 and Low HO-1 Environment. Antioxidants. 2020; 9(7):598. https://doi.org/10.3390/antiox9070598

Chicago/Turabian Style

Sanchez-Aranguren, Lissette C., Homira Rezai, Shakil Ahmad, Faisal A. Alzahrani, Anna Sparatore, Keqing Wang, and Asif Ahmed. 2020. "MZe786 Rescues Cardiac Mitochondrial Activity in High sFlt-1 and Low HO-1 Environment" Antioxidants 9, no. 7: 598. https://doi.org/10.3390/antiox9070598

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