MZe786, a hydrogen sulfide-releasing aspirin prevents preeclampsia in heme oxygenase-1 haplodeficient pregnancy under high soluble flt-1 environment

Homira Rezai, Shakil Ahmad, Faisal A. Alzahrani, Lissette Sanchez-Aranguren, Irundika HK. Dias, Swati Agrawal, Anna Sparatore, Keqing Wang, Asif Ahmed

Research output: Contribution to journalArticlepeer-review

Abstract

Preeclampsia affects one in twelve of the 130 million pregnancies a year. The lack of an effective therapeutic to prevent or treat it is responsible for an annual global cost burden of 100 billion US dollars. Preeclampsia also affects these women later in life as it is a recognised risk factor for cardiovascular disease, stroke and vascular dementia. Our laboratory demonstrated that preeclampsia is associated with high soluble fms-like tyrosine kinase 1 (sFlt-1) and low heme oxygenase-1 (HO1/Hmox1) expression. Here we sought to determine the therapeutic value of a novel H 2S-releasing aspirin (MZe786) in HO-1 haploid deficient (Hmox1 +/−) pregnant mice in a high sFlt-1 environment. Pregnant Hmox1 +/− mice were injected with adenovirus encoding sFlt-1 or control virus at gestation day E11.5. Subsequently, Hmox1 +/− dams were treated daily with a number of treatment regimens until E17.5, when maternal and fetal outcomes were assessed. Here we show that HO-1 compromised mice in a high sFlt-1 environment during pregnancy exhibit severe preeclampsia signs and a reduction in antioxidant genes. MZe786 ameliorates preeclampsia by reducing hypertension and renal damage possibly by stimulating antioxidant genes. MZe786 also improved fetal outcome in comparison with aspirin alone and appears to be a better therapeutic agent at preventing preeclampsia than aspirin alone.

Original languageEnglish
Article number101768
JournalRedox Biology
Volume38
Early online date24 Oct 2020
DOIs
Publication statusPublished - Jan 2021

Bibliographical note

© 2020 The Author(s). Creative Commons Attribution 4.0 International (CC BY 4.0)

Funding: This work was supported by grants from the Medical Research Council (G0700288) to AA and grant (FP-52-42) from the Deanship of Scientific Affairs, King Abdulaziz University, Jeddah, Saudi Arabia to FAA and AA

Keywords

  • Heme oxygenase-1
  • Hydrogen sulfide
  • Hypertension
  • Preeclampsia
  • sFlt-1

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