Mitochondria Targeted Antioxidant Significantly Alleviates Preeclampsia Caused by 11β-HSD2 Dysfunction via OPA1 and MtDNA Maintenance

Long, Jing; Huang, Yan; Tang, Zhonghai; Shan, Yali; Ding, Feng; Wang, Wen-Qin; Liu, Juan; Huang, Ying; Gu, Hang; Guo, Dan; Yao, Ruojin; Ni, Xin

doi:10.3390/antiox11081505

Cited by 8 publications

(15 citation statements)

References 75 publications

(109 reference statements)

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“…[ 109 ]. In another study, MitoTEMPO improved placental mtDNA stability and mitochondrial dynamics in a PE-like rat model [ 161 ]. In cell culture, it reduced mitochondrial ROS production in HUVECs treated with plasma from PE patients.…”

Section: Potential For Mitochondrial Targeting Therapies In Preeclampsiamentioning

confidence: 99%

Placental Mitochondrial Function and Dysfunction in Preeclampsia

Jahan

Vasam

Green

et al. 2023

IJMS

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The placenta is a vital organ of pregnancy, regulating adaptation to pregnancy, gestational parent/fetal exchange, and ultimately, fetal development and growth. Not surprisingly, in cases of placental dysfunction—where aspects of placental development or function become compromised—adverse pregnancy outcomes can result. One common placenta-mediated disorder of pregnancy is preeclampsia (PE), a hypertensive disorder of pregnancy with a highly heterogeneous clinical presentation. The wide array of clinical characteristics observed in pregnant individuals and neonates of a PE pregnancy are likely the result of distinct forms of placental pathology underlying the PE diagnosis, explaining why no one common intervention has proven effective in the prevention or treatment of PE. The historical paradigm of placental pathology in PE highlights an important role for utero–placental malperfusion, placental hypoxia and oxidative stress, and a critical role for placental mitochondrial dysfunction in the pathogenesis and progression of the disease. In the current review, the evidence of placental mitochondrial dysfunction in the context of PE will be summarized, highlighting how altered mitochondrial function may be a common feature across distinct PE subtypes. Further, advances in this field of study and therapeutic targeting of mitochondria as a promising intervention for PE will be discussed.

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Section: Potential For Mitochondrial Targeting Therapies In Preeclampsiamentioning

confidence: 99%

Placental Mitochondrial Function and Dysfunction in Preeclampsia

Jahan

Vasam

Green

et al. 2023

IJMS

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“…MitoTEMPO (Sigma-Aldrich, St. Louis, MO, USA) was dissolved in saline. The dosage of DEX and mitoTEMPO was chosen based on our previous studies [13,27]. Blood pressure was measured in rats, as described previously [13,27].…”

Section: Animalsmentioning

confidence: 99%

“…The dosage of DEX and mitoTEMPO was chosen based on our previous studies [13,27]. Blood pressure was measured in rats, as described previously [13,27]. Placental blood flow was detected by Doppler ultrasonography on GD19.5.…”

Section: Animalsmentioning

confidence: 99%

“…As previously mentioned, the mean arterial pressure (MAP) of each dam was measured every two days GD9.5-17.5 using the tail-cuff system (BP-300A automatic noninvasive blood pressure measurement system, Techmen software Ltd., Chengdu, China) [13,27]. Systolic blood pressure (SBP) was measured by right carotid artery intubation in pregnant rats at GD20.5, and recorded by the computer collecting and disposing of the system of organic signals (BL-420N, Techmen software Ltd., Chengdu, China).…”

Section: Measurement Of Blood Pressurementioning

confidence: 99%

“…As previously mentioned, utero-placental blood flow was measured by Doppler ultrasonography (Vevo 2100, FuJiFilm, Tokyo, Japan) on GD19.5 [27]. First, the rats were placed in an airtight box and anesthetized with 5% isoflurane.…”

Section: Uteroplacental Blood Perfusion Measurementmentioning

confidence: 99%

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Mitochondrial ROS Accumulation Contributes to Maternal Hypertension and Impaired Remodeling of Spiral Artery but Not IUGR in a Rat PE Model Caused by Maternal Glucocorticoid Exposure

et al. 2023

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Increased maternal glucocorticoid levels have been implicated as a risk factor for preeclampsia (PE) development. We found that pregnant rats exposed to dexamethasone (DEX) showed hallmarks of PE features, impaired spiral artery (SA) remodeling, and elevated circulatory levels of sFlt1, sEng IL-1β, and TNFα. Abnormal mitochondrial morphology and mitochondrial dysfunction in placentas occurred in DEX rats. Omics showed that a large spectrum of placental signaling pathways, including oxidative phosphorylation (OXPHOS), energy metabolism, inflammation, and insulin-like growth factor (IGF) system were affected in DEX rats. MitoTEMPO, a mitochondria-targeted antioxidant, alleviated maternal hypertension and renal damage, and improved SA remodeling, uteroplacental blood flow, and the placental vasculature network. It reversed several pathways, including OXPHOS and glutathione pathways. Moreover, DEX-induced impaired functions of human extravillous trophoblasts were associated with excess ROS caused by mitochondrial dysfunction. However, scavenging excess ROS did not improve intrauterine growth retardation (IUGR), and elevated circulatory sFlt1, sEng, IL-1β, and TNFα levels in DEX rats. Our data indicate that excess mitochondrial ROS contributes to trophoblast dysfunction, impaired SA remodeling, reduced uteroplacental blood flow, and maternal hypertension in the DEX-induced PE model, while increased sFlt1 and sEng levels and IUGR might be associated with inflammation and an impaired energy metabolism and IGF system.

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