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Select item 44498351.

Bioactive Factors in Uteroplacental and Systemic Circulation Link Placental Ischemia to Generalized Vascular Dysfunction in Hypertensive Pregnancy and Preeclampsia

Dania A. Shah, Raouf A. Khalil

Biochem Pharmacol. Author manuscript; available in PMC 2016 Jun 15.

Published in final edited form as: Biochem Pharmacol. 2015 Jun 15; 95(4): 211–226. Published online 2015 Apr 24. doi: 10.1016/j.bcp.2015.04.012

PMCID:: PMC4449835

Abstract Article PDF–613K

Select item 72600052.

RNA interference therapeutics targeting angiotensinogen ameliorate preeclamptic phenotype in rodent models

Nadine Haase, Donald J. Foster, Mark W. Cunningham, Julia Bercher, Tuyen Nguyen, Svetlana Shulga-Morskaya, Stuart Milstein, Sarfraz Shaikh, Jeff Rollins, Michaela Golic, Florian Herse, Kristin Kräker, Ivo Bendix, Meray Serdar, Hanna Napieczynska, Arnd Heuser, Alexandra Gellhaus, Kristin Thiele, Gerd Wallukat, Dominik N. Müller, Babbette LaMarca, Ralf Dechend

J Clin Invest. 2020 Jun 1; 130(6): 2928–2942. Published online 2020 Apr 27. doi: 10.1172/JCI99417

PMCID:: PMC7260005

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Select item 75092723.

Vascular mechanisms and molecular targets in hypertensive pregnancy and preeclampsia

Hongmei Qu, Raouf A. Khalil

Am J Physiol Heart Circ Physiol. 2020 Sep 1; 319(3): H661–H681. Published online 2020 Aug 7. doi: 10.1152/ajpheart.00202.2020

PMCID:: PMC7509272

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Select item 57054644.

Angiogenic Imbalance and Diminished Matrix Metalloproteinase-2 and -9 Underlie Regional Decreases in Uteroplacental Vascularization and Feto-placental Growth in Hypertensive Pregnancy

Carlos A. Dias-Junior, Juanjuan Chen, Ning Cui, Charles L. Chiang, Minglin Zhu, Zongli Ren, Jose S. Possomato-Vieira, Raouf A. Khalil

Biochem Pharmacol. Author manuscript; available in PMC 2018 Dec 15.

Published in final edited form as: Biochem Pharmacol. 2017 Dec 15; 146: 101–116. Published online 2017 Sep 11. doi: 10.1016/j.bcp.2017.09.005

PMCID:: PMC5705464

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Select item 48671115.

Placental growth factor reduces blood pressure in a uteroplacental ischemia model of preeclampsia in non-human primates

Angela Makris, Kristen R Yeung, Shirlene M Lim, Neroli Sunderland, Scott Heffernan, John F Thompson, Jim Iliopoulos, Murray C Killingsworth, Jim Yong, Bei Xu, Robert F Ogle, Ravi Thadhani, S. Ananth Karumanchi, Annemarie Hennessy

Hypertension. Author manuscript; available in PMC 2016 Dec 1.

Published in final edited form as: Hypertension. 2016 Jun; 67(6): 1263–1272. Published online 2016 Apr 18. doi: 10.1161/HYPERTENSIONAHA.116.07286

PMCID:: PMC4867111

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Placental growth factor reverses decreased vascular and uteroplacental MMP-2 and MMP-9 and increased MMP-1 and MMP-7 and collagen types I and IV in hypertensive pregnancy

Zongli Ren, Ning Cui, Minglin Zhu, Raouf A. Khalil

Am J Physiol Heart Circ Physiol. 2018 Jul 1; 315(1): H33–H47. Published online 2018 Mar 23. doi: 10.1152/ajpheart.00045.2018

PMCID:: PMC6087780

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Select item 85335927.

Role of the Uteroplacental Renin–Angiotensin System in Placental Development and Function, and Its Implication in the Preeclampsia Pathogenesis

Lucile Yart, Edith Roset Bahmanyar, Marie Cohen, Begoña Martinez de Tejada

Biomedicines. 2021 Oct; 9(10): 1332. Published online 2021 Sep 27. doi: 10.3390/biomedicines9101332

PMCID:: PMC8533592

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Increased vascular and uteroplacental matrix metalloproteinase-1 and -7 levels and collagen type I deposition in hypertension in pregnancy: role of TNF-α

Wei Li, Ning Cui, Marc Q. Mazzuca, Karina M. Mata, Raouf A. Khalil

Am J Physiol Heart Circ Physiol. 2017 Sep 1; 313(3): H491–H507. Published online 2017 Jun 16. doi: 10.1152/ajpheart.00207.2017

PMCID:: PMC5625170

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TNFα Blockade Reverses Vascular and Uteroplacental Matrix Metalloproteinases Imbalance and Collagen Accumulation in Hypertensive Pregnant Rats

Zongli Ren, Ning Cui, Minglin Zhu, Raouf A. Khalil

Biochem Pharmacol. Author manuscript; available in PMC 2022 Nov 1.

Published in final edited form as: Biochem Pharmacol. 2021 Nov; 193: 114790. Published online 2021 Oct 1. doi: 10.1016/j.bcp.2021.114790

PMCID:: PMC8606001

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Matrix Metalloproteinases in Normal Pregnancy and Preeclampsia

Juanjuan Chen, Raouf A. Khalil

Prog Mol Biol Transl Sci. Author manuscript; available in PMC 2018 May 22.

Published in final edited form as: Prog Mol Biol Transl Sci. 2017; 148: 87–165. Published online 2017 May 22. doi: 10.1016/bs.pmbts.2017.04.001

PMCID:: PMC5548443

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Defective Uteroplacental Vascular Remodeling in Preeclampsia: Key Molecular Factors Leading to Long Term Cardiovascular Disease

Kirim Hong, Soo Hyun Kim, Dong Hyun Cha, Hee Jin Park

Int J Mol Sci. 2021 Oct; 22(20): 11202. Published online 2021 Oct 18. doi: 10.3390/ijms222011202

PMCID:: PMC8539609

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The etiology of preeclampsia

Eunjung JUNG, Roberto ROMERO, Lami YEO, Nardhy GOMEZ-LOPEZ, Piya CHAEMSAITHONG, Adithep JAOVISIDHA, Offer EREZ

Am J Obstet Gynecol. Author manuscript; available in PMC 2023 Feb 1.

Published in final edited form as: Am J Obstet Gynecol. 2022 Feb; 226(2 Suppl): S844–S866. doi: 10.1016/j.ajog.2021.11.1356

PMCID:: PMC8988238

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Effect of Oxidative Stress on the Estrogen-NOS-NO-K_Ca Channel Pathway in Uteroplacental Dysfunction: Its Implication in Pregnancy Complications

Xiang-Qun Hu, Rui Song, Lubo Zhang

Oxid Med Cell Longev. 2019; 2019: 9194269. Published online 2019 Feb 10. doi: 10.1155/2019/9194269

PMCID:: PMC6387699

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Uteroplacental Circulation in Normal Pregnancy and Preeclampsia: Functional Adaptation and Maladaptation

Xiangqun Hu, Lubo Zhang

Int J Mol Sci. 2021 Aug; 22(16): 8622. Published online 2021 Aug 11. doi: 10.3390/ijms22168622

PMCID:: PMC8395300

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Select item 608814515.

Gestational Hypoxia and Developmental Plasticity

Charles A. Ducsay, Ravi Goyal, William J. Pearce, Sean Wilson, Xiang-Qun Hu, Lubo Zhang

Physiol Rev. 2018 Jul 1; 98(3): 1241–1334. Published online 2018 May 2. doi: 10.1152/physrev.00043.2017

PMCID:: PMC6088145

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MicroRNAs in Uteroplacental Vascular Dysfunction

Xiang-Qun Hu, Lubo Zhang

Cells. 2019 Nov; 8(11): 1344. Published online 2019 Oct 29. doi: 10.3390/cells8111344

PMCID:: PMC6912833

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Preeclampsia Link to Gestational Hypoxia

Wen Tong, Dino A. Giussani

J Dev Orig Health Dis. Author manuscript; available in PMC 2019 Jul 25.

Published in final edited form as: J Dev Orig Health Dis. 2019 Jun; 10(3): 322–333. Published online 2019 Apr 10. doi: 10.1017/S204017441900014X

PMCID:: PMC6658216

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Ischemia-Modified Albumin: Origins and Clinical Implications

Alla Shevtsova, Iuliia Gordiienko, Viktoriia Tkachenko, Galyna Ushakova

Dis Markers. 2021; 2021: 9945424. Published online 2021 Jul 19. doi: 10.1155/2021/9945424

PMCID:: PMC8315882

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Mechanisms of Endothelial Dysfunction in Hypertensive Pregnancy and Preeclampsia

José S. Possomato-Vieira, Raouf A. Khalil

Adv Pharmacol. Author manuscript; available in PMC 2017 Jun 14.

Published in final edited form as: Adv Pharmacol. 2016; 77: 361–431. Published online 2016 Jun 14. doi: 10.1016/bs.apha.2016.04.008

PMCID:: PMC4965238

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Select item 795918920.

Preeclampsia: Linking Placental Ischemia with Maternal Endothelial and Vascular Dysfunction

Bhavisha A. Bakrania, Frank T. Spradley, Heather A. Drummond, Babbette LaMarca, Michael J. Ryan, Joey P. Granger

Compr Physiol. Author manuscript; available in PMC 2021 Mar 15.

Published in final edited form as: Compr Physiol. 2020 Dec 9; 11(1): 1315–1349. Published online 2020 Dec 9. doi: 10.1002/cphy.c200008

PMCID:: PMC7959189

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PMC Images search for uteroplacental ischemia

Fig. 2.

Risk factors, uteroplacental maladaptations, and placental ischemia. Predisposing genetic polymorphisms, demographic characteristics, obesity, sedentary lifestyle, high-sodium low-calcium diet, and environmental pollutants could cause maladaptations in the uteroplacental immune response, integrins and adhesion molecules, matrix metalloproteinases (MMPs), and microRNAs. The uteroplacental maladaptations in turn lead to defective placentation and placental ischemia/hypoxia. BMI, body mass index; HLA-C, -E, and -G, histocompatibility complex molecules; NK, natural killer.

Vascular mechanisms and molecular targets in hypertensive pregnancy and preeclampsia

Am J Physiol Heart Circ Physiol. 2020 Sep 1;319(3):H661-H681.
Figure 2:

Effects of Uteroplacental ischemia (UPI) on blood pressure a) systolic (SBP) and b) diastolic (DBP) blood pressure (mmHg) during sleep and c) systolic and d) diastolic blood pressure during awake periods and e) proteinuria (expressed as the spot urinary protein: urinary creatinine ratio) on protocol days 3, 6, 10 and 14 after uteroplacental ischemia. Data for the control (n=4, green line), treated (n=3, red line) and total group (n=7, black line) is demonstrated on each graph. * indicates a significant difference of the grouped result compared to baseline blood pressure p<0.001.

Placental growth factor reduces blood pressure in a uteroplacental ischemia model of preeclampsia in non-human primates

Hypertension. ;67(6):1263-1272.
FIGURE 2Mean arterial pressure in response to 17-OHPC in RUPP rat model

Mean arterial pressure in NP rats and RUPP rats ± 17-OHPC at day 19 of gestation P < .05 vs NP rats; P < .05 vs RUPP rats (asterisk).
NP, normal pregnant; RUPP, reduction of uteroplacental perfusion; 17-OHPC, 17-alpha-hydroxyprogesterone caproate.

Progesterone blunts vascular endothelial cell secretion of endothelin-1 in response to placental ischemia

Am J Obstet Gynecol. ;209(1):44.e1-44.e6.
Figure 5.hsiRNAsFLT1-2283/2519 treatment lowers sFLT1 serum levels and normalize blood pressure and proteinuria in NHP model of PE.

a. The timeline for uteroplacental ischemia induction (UPI) model of PE in pregnant baboon. Data collected for hsiRNA^sFLT1-2283/2519-treated UPI animals (n=3, mean ±SEM), PBS treated UPI animals (n=6, mean ±SEM), and controls (sham surgery, no UPI) (n=3, mean ±SEM) (***P<0.001, two-way ANOVA; UPI vs hsiRNA^sFLT1). b. sFLT1 serum concentration measured by ELISA c. Systolic blood pressure (BP, awake) plotted from telemetry recordings. d. Proteinuria presented as spot protein/creatinine ratio.

RNAi Modulation of Placental sFLT1 for the Treatment of Preeclampsia.

Nat Biotechnol. :10.1038/nbt.4297.