Role of aspirin‐triggered lipoxin A4, aspirin, and salicylic acid in the modulation of the oxidative and inflammatory responses induced by plasma from women with pre‐eclampsia

Gil-Villa, Aura María; Alvarez, Angela M.; Velásquez-Berrío, Manuela; Rojas‐López, Mauricio; J, Ángela P. Cadavid

doi:10.1111/aji.13207

Cited by 16 publications

(13 citation statements)

References 77 publications

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“…Importantly, aspirin-acetylated COX2 may generate lipoxins from arachidonic acid [ 234 ], or “aspirin-triggered lipoxins” (ATLs or lipoxin-A4). These ATLs are potent anti-inflammatory mediators able to decrease oxidative stress and inflammation evoked by the plasma of women affected with PE [ 235 ]. ATLs could also stimulate the release of NO, by activating both eNOS and iNOS [ 235 ].…”

Section: Therapeutic Perspectives Targeting Oxidative Stress and No/ementioning

confidence: 99%

“…These ATLs are potent anti-inflammatory mediators able to decrease oxidative stress and inflammation evoked by the plasma of women affected with PE [ 235 ]. ATLs could also stimulate the release of NO, by activating both eNOS and iNOS [ 235 ]. In addition, aspirin is able to acetylate and stimulates the enzymatic activity of eNOS, and promotes a release of NO from endothelial cells [ 236 ].…”

Section: Therapeutic Perspectives Targeting Oxidative Stress and No/ementioning

confidence: 99%

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Role of oxidative stress in the dysfunction of the placental endothelial nitric oxide synthase in preeclampsia

et al. 2021

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Preeclampsia (PE) is a multifactorial pregnancy disease, characterized by new-onset gestational hypertension with (or without) proteinuria or end-organ failure, exclusively observed in humans. It is a leading cause of maternal morbidity affecting 3–7% of pregnant women worldwide. PE pathophysiology could result from abnormal placentation due to a defective trophoblastic invasion and an impaired remodeling of uterine spiral arteries, leading to a poor adaptation of utero-placental circulation. This would be associated with hypoxia/reoxygenation phenomena, oxygen gradient fluctuations, altered antioxidant capacity, oxidative stress, and reduced nitric oxide (NO) bioavailability. This results in part from the reaction of NO with the radical anion superoxide (O 2 •− ), which produces peroxynitrite ONOO - , a powerful pro-oxidant and inflammatory agent. Another mechanism is the progressive inhibition of the placental endothelial nitric oxide synthase (eNOS) by oxidative stress, which results in eNOS uncoupling via several events such as a depletion of the eNOS substrate L-arginine due to increased arginase activity, an oxidation of the eNOS cofactor tetrahydrobiopterin (BH4), or eNOS post-translational modifications (for instance by S -glutathionylation). The uncoupling of eNOS triggers a switch of its activity from a NO-producing enzyme to a NADPH oxidase-like system generating O 2 •− , thereby potentiating ROS production and oxidative stress. Moreover, in PE placentas, eNOS could be post-translationally modified by lipid peroxidation-derived aldehydes such as 4-oxononenal (ONE) a highly bioreactive agent, able to inhibit eNOS activity and NO production. This review summarizes the dysfunction of placental eNOS evoked by oxidative stress and lipid peroxidation products, and the potential consequences on PE pathogenesis.

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Section: Therapeutic Perspectives Targeting Oxidative Stress and No/ementioning

confidence: 99%

Section: Therapeutic Perspectives Targeting Oxidative Stress and No/ementioning

confidence: 99%

Role of oxidative stress in the dysfunction of the placental endothelial nitric oxide synthase in preeclampsia

et al. 2021

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“…Apart from its conventional antithrombotic activity, aspirin has a modest ability of scavenging superoxide and it also contributes to the release of NO from the endothelium, which might result from the direct acetylation of eNOS [ 164 ]. Aspirin-triggered lipoxins inhibit the NADPH oxidase-mediated generation of ROS and nitrotyrosine in the endothelial cells [ 165 , 166 ]. Heparin has also been reported to reduce the plasma level of peroxides and increase the activity of SOD and catalase in red blood cells [ 167 ].…”

Section: Antioxidant Therapies In Pementioning

confidence: 99%

Oxidative Stress and Preeclampsia-Associated Prothrombotic State

et al. 2020

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Preeclampsia (PE) is a common obstetric disease characterized by hypertension, proteinuria, and multi-system dysfunction. It endangers both maternal and fetal health. Although hemostasis is critical for preventing bleeding complications during pregnancy, delivery, and post-partum, PE patients often develop a severe prothrombotic state, potentially resulting in life-threatening thrombosis and thromboembolism. The cause of this thrombotic complication is multi-factorial, involving endothelial cells, platelets, adhesive ligands, coagulation, and fibrinolysis. Increasing evidence has shown that hemostatic cells and factors undergo oxidative modifications during the systemic inflammation found in PE patients. However, it is largely unknown how these oxidative modifications of hemostasis contribute to development of the PE-associated prothrombotic state. This knowledge gap has significantly hindered the development of predictive markers, preventive measures, and therapeutic agents to protect women during pregnancy. Here we summarize reports in the literature regarding the effects of oxidative stress and antioxidants on systemic hemostasis, with emphasis on the condition of PE.

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“…Human umbilical vein endothelial cells (HUVEC) were isolated from umbilical cords obtained from uncomplicated pregnancies based on a modified protocol by Jaffe et al (1973) and as previously described (Velásquez et al, 2019;Gil-Villa et al, 2020). In brief, umbilical veins were perfused with 100 µg/ml type I collagenase (Invitrogen, Waltham, MA, United States) and incubated for 20 min at 37 • C. Cells were recovered, and after centrifugation (50 g for 5 min), they were seeded in the endothelial cell growth medium (Promocell, Heidelberg, Germany) supplemented with 2% fetal bovine serum (FBS, Gibco, Waltham, MA, United States), 100 U/ml penicillin (Sigma Aldrich, Missouri, United States), 50 µg/ml gentamicin (Genfar, Bogotá, Colombia), and 0.25 µg/ml amphotericin B (Vitalis, Bogotá, Colombia).…”

Section: Cell Culturementioning

confidence: 99%

Antiphospholipid Antibodies From Women With Pregnancy Morbidity and Vascular Thrombosis Induce Endothelial Mitochondrial Dysfunction, mTOR Activation, and Autophagy

et al. 2021

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Antiphospholipid syndrome (APS) is an autoimmune disease characterized by thrombosis and pregnancy morbidity (PM) obstetric events together with persistent high titers of circulating antiphospholipid antibodies (aPL). Several mechanisms that explain the development of thrombosis and PM in APS include the association of aPL with alterations in the coagulation cascade and inflammatory events. Other mechanisms disturbing cellular homeostases, such as mitochondrial dysfunction, autophagy, and cell proliferation, have been described in other autoimmune diseases. Therefore, the objective of this study was to investigate the impact of aPL from different patient populations on endothelial cell mitochondrial function, activation of the mammalian target of rapamycin (mTOR) and autophagy pathways, and cellular growth. Using an in vitro model, human umbilical vein endothelial cells (HUVECs) were treated with polyclonal immunoglobulin G (IgG) purified from the serum of women with both PM and vascular thrombosis (PM/VT), with VT only (VT), or with PM and non-criteria aPL (seronegative-obstetric APS, SN-OAPS). We included IgG from women with PM without aPL (PM/aPL-) and healthy women with previous uncomplicated pregnancies (normal human serum, NHS) as control groups. Mitochondrial function, mTOR activation, autophagy, and cell proliferation were evaluated by Western blotting, flow cytometry, and functional assays. IgG from women with PM/VT increased HUVEC mitochondrial hyperpolarization and activation of the mTOR and autophagic pathways, while IgG from patients with VT induced endothelial autophagy and cell proliferation in the absence of elevated mTOR activity or mitochondrial dysfunction. IgG from the SN-OAPS patient group had no effect on any of these HUVEC responses. In conclusion, aPL from women with PM and vascular events induce cellular stress evidenced by mitochondrial hyperpolarization and increased activation of the mTOR and autophagic pathways which may play a role in the pathogenesis of obstetric APS.

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Role of aspirin‐triggered lipoxin A4, aspirin, and salicylic acid in the modulation of the oxidative and inflammatory responses induced by plasma from women with pre‐eclampsia

Cited by 16 publications

References 77 publications

Role of oxidative stress in the dysfunction of the placental endothelial nitric oxide synthase in preeclampsia

Role of oxidative stress in the dysfunction of the placental endothelial nitric oxide synthase in preeclampsia

Oxidative Stress and Preeclampsia-Associated Prothrombotic State

Antiphospholipid Antibodies From Women With Pregnancy Morbidity and Vascular Thrombosis Induce Endothelial Mitochondrial Dysfunction, mTOR Activation, and Autophagy

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