ArticleBiochemical pharmacology2021
TNFα blockade reverses vascular and uteroplacental matrix metalloproteinases imbalance and collagen accumulation in hypertensive pregnant rats.
Article in Biochemical pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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10 citing papers in PubMed, 1 synthesis or guideline pooled it, 10 citations in OpenAlex.
- Reduced uterine perfusion pressure as a model for preeclampsia and fetal growth restriction in murine: a systematic review and meta-analysis.American journal of physiology. Heart and circulatory physiology · 2024Pooled it
- Aberrant Uteroplacental and Vascular Signaling and Remodeling by Matrix Metalloproteinases in Pregnancy-Related Hypertension and Preeclampsia.Biomolecules · 2026Review
- Caspase-3/GSDME-Mediated Trophoblast Pyroptosis and Reciprocal Macrophage Polarization Contribute to Inflammation in Early-Onset Preeclampsia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Analysis of immune-related biomarkers in amniotic fluid embolism by sequencing data and bioinformatics.BMC pregnancy and childbirth · 2025Article
- Comprehensive identification of immune-related biomarkers and therapeutic targets in preeclampsia: integrative bioinformatics and experimental validation.BMC pregnancy and childbirth · 2025Article
- Extracellular matrix gene set and microRNA network in intestinal ischemia-reperfusion injury: Insights from RNA sequencing for diagnosis and therapy.World journal of gastrointestinal surgery · 2025Review
- Increased uterine arterial tone, stiffness and remodeling with augmented matrix metalloproteinase-1 and -7 in uteroplacental ischemia-induced hypertensive pregnancy.Biochemical pharmacology · 2024Article
- Preeclampsia at term: evidence of disease heterogeneity based on the profile of circulating cytokines and angiogenic factors.American journal of obstetrics and gynecology · 2024Article
- Regulation of vascular angiotensin II type 1 and type 2 receptor and angiotensin-(1-7)/MasR signaling in normal and hypertensive pregnancy.Biochemical pharmacology · 2024Review
- Sodium Nitrite Attenuates Reduced Activity of Vascular Matrix Metalloproteinase-2 and Vascular Hyper-Reactivity and Increased Systolic Blood Pressure Induced by the Placental Ischemia Model of Preeclampsia in Anesthetized Rats.International journal of molecular sciences · 2023Article
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Authors and funding
4 authors at 1 institution in 1 country.
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Abstract
Preeclampsia is a pregnancy-related disorder of maternal hypertension-in-pregnancy (HTN-Preg) and often fetal growth restriction (FGR). Placental ischemia could be an initiating event leading to inadequate vascular and uteroplacental remodeling and HTN-Preg; however, the molecular targets are unclear. To test the hypothesis that placental ischemia-induced release of proinflammatory cytokines target vascular and uteroplacental matrix metalloproteinases (MMPs), we tested if infusing TNFα (200 ng/kg/day) in day-14 pregnant (Preg) rats causes MMP imbalance and collagen accumulation, and if infusing TNFα decoy receptor Etanercept (0.4 mg/kg/day) in HTN-Preg rats with reduced uteroplacental perfusion pressure (RUPP) reverses MMP imbalance and collagen accumulation. On gestational day-19, blood pressure (BP) was higher in Preg + TNFα and RUPP vs Preg rats, and restored in RUPP + Etanercept rats. Gelatin zymography and Western blots revealed decreases in MMP-2 and MMP-9 and increases in MMP-1 and MMP-7 in aorta, uterus and placenta of Preg + TNFα and RUPP, that were reversed in RUPP + Etanercept rats. Collagen-I and IV were abundant in Preg + TNFα and RUPP, and were decreased in RUPP + Etanercept rats. The litter size, uterine, placenta, and pup weight were markedly reduced in RUPP, insignificantly reduced in Preg + TNFα, and slightly improved in RUPP + Etanercept rats. Thus TNFα blockade reverses the decreases in vascular and uteroplacental MMP-2 and MMP-9, and the increases in MMP-1, MMP-7 and accumulation of collagen-I and IV induced by placental ischemia and TNFα in HTN-Preg rats. Targeting TNFα using cytokine antagonists, or MMPs using MMP modulators could rectify MMP imbalance and collagen accumulation, restore vascular and uteroplacental remodeling, and improve BP in HTN-Preg and preeclampsia.
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