Supraphysiological Role of Melatonin Over Vascular Dysfunction of Pregnancy, a New Therapeutic Agent?

Hypertension can be induced by the disruption of factors in blood pressure regulation. This includes several systems such as Neurohumoral, Renin-angiotensin-aldosterone, the Circadian clock, and melatonin production, which can induce elevation and non-dipping blood pressure. Melatonin has a supraphysiological role as a chronobiotic agent and modulates vascular system processes via pro/antiangiogenic factors, inflammation, the immune system, and oxidative stress regulation. An elevation of melatonin production is observed during pregnancy, modulating the placenta and fetus’s physiological functions. Their impairment production can induce temporal desynchronization of cell proliferation, differentiation, or invasion from trophoblast cells results in vascular insufficiencies, elevating the risk of poor fetal/placental development. Several genes are associated with vascular disease and hypertension during pregnancy via impaired inflammatory response, hypoxia, and oxidative stress, such as cytokines/chemokines IL-1β, IL-6, IL-8, and impairment expression in endothelial cells/VSMCs of HIF1α and eNOS genes. Pathological placentas showed differentially expressed genes (DEG), including vascular genes as CITED2, VEGF, PL-II, PIGF, sFLT-1, and sENG, oncogene JUNB, scaffolding protein CUL7, GPER1, and the pathways of SIRT/AMPK and MAPK/ERK. Additionally, we observed modification of subunits of NADPH oxidase and extracellular matrix elements, i.e., Glypican and Heparanase and KCa channel. Mothers with a low level of melatonin showed low production of proangiogenic factor VEGF, increasing the risk of preeclampsia, premature birth, and abortion. In contrast, melatonin supplementation can reduce systolic pressure, prevent oxidative stress, induce the activation of the antioxidants system, and lessen proteinuria and serum level of sFlt-1. Moreover, melatonin can repair the endothelial damage from preeclampsia at the placenta level, increasing PIGF, Nrf-2, HO-1 production and reducing critical markers of vascular injury during the pregnancy. Melatonin also restores the umbilical and uterine blood flow after oxidative stress and inhibits vascular inflammation and VCAM-1, Activin-A, and sEng production. The beneficial effects of melatonin over pathological pregnancies can be partially observed in normal pregnancies, suggesting the dual role of/over placental physiology could contribute to protection and have therapeutic applications in vascular pathologies of pregnancies in the future.

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The Role of NFκB in Healthy and Preeclamptic Placenta: Trophoblasts in the Spotlight

International Journal of Molecular Sciences ◽

10.3390/ijms21051775 ◽

2020 ◽

Vol 21 (5) ◽

pp. 1775 ◽

Cited By ~ 8

Author(s):

Brooke Armistead ◽

Leena Kadam ◽

Sascha Drewlo ◽

Hamid-Reza Kohan-Ghadr

Keyword(s):

Oxidative Stress ◽

Fetal Growth ◽

Fetal Growth Restriction ◽

Growth And Development ◽

Protein Family ◽

Growth Restriction ◽

Placental Development ◽

Critical Organ ◽

And Oxidative Stress

The NFκB protein family regulates numerous pathways within the cell—including inflammation, hypoxia, angiogenesis and oxidative stress—all of which are implicated in placental development. The placenta is a critical organ that develops during pregnancy that primarily functions to supply and transport the nutrients required for fetal growth and development. Abnormal placental development can be observed in numerous disorders during pregnancy, including fetal growth restriction, miscarriage, and preeclampsia (PE). NFκB is highly expressed in the placentas of women with PE, however its contributions to the syndrome are not fully understood. In this review we discuss the molecular actions and related pathways of NFκB in the placenta and highlight areas of research that need attention

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Rosiglitazone Decreases Blood Pressure in Female Dahl Rats: Role of Nitric Oxide and Oxidative Stress

The FASEB Journal ◽

10.1096/fasebj.22.1_supplement.941.16 ◽

2008 ◽

Vol 22 (S1) ◽

Author(s):

Julio C. Sartori‐Valinotti ◽

Michael J. Ryan ◽

Huimin Zhang ◽

Jane F. Reckelhoff

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Blood Pressure ◽

And Oxidative Stress

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Clinical Experience with Ivabradine in Acute Heart Failure

Cardiology ◽

10.1159/000444845 ◽

2016 ◽

Vol 134 (3) ◽

pp. 372-374 ◽

Cited By ~ 10

Author(s):

Marina Pascual Izco ◽

Gonzalo Luis Alonso Salinas ◽

Marcelo Sanmartín Fernández ◽

Hugo Del Castillo Carnevalli ◽

Manuel Jiménez Mena ◽

...

Keyword(s):

Oxidative Stress ◽

Heart Failure ◽

Blood Pressure ◽

Randomized Trials ◽

Beta Blockers ◽

Treatment Results ◽

Absolute Reduction ◽

Attractive Option ◽

And Oxidative Stress

Objective: Ivabradine has been shown to improve symptoms and to reduce rehospitalization and mortality in patients with severe chronic heart failure (HF). Its indication in acute HF is not clear. Acute HF patients could also benefit from HR reduction, as myocardial consumption and oxidative stress are related to tachycardia. Moreover, beta-blockers are contraindicated in cardiogenic shock and should not be initiated with congestive signs. Accordingly, we evaluated the role of ivabradine in acute HF patients. Methods: This was a retrospective analysis of 29 consecutive patients treated for acute HF in the Cardiac ICU, and for whom ivabradine was initiated during hospitalization between January 2011 and January 2014. All patients were in sinus rhythm and had a heart rate (HR) >70 bpm. Catecholamine use was necessary in 16 patients (57.1%) during the hospitalization, in 14 (87.5%) of these before ivabradine treatment. Results: Systolic blood pressure showed no variation during the first 24 h of ivabradine administration or at discharge. HR showed an absolute reduction of 10 bpm at 6 h (p < 0.001), 11 bpm at 24 h (p = 0.004) and 19 bpm (p < 0.001) at discharge. No episodes of significant bradycardia or hypotension were recorded after starting the drug. Conclusions: HR reduction with ivabradine in acute HF is well tolerated. It represents an attractive option, especially when there is excessive catecholamine-related tachycardia; this should be appropriately evaluated in randomized trials.

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ROLE OF RENIN-ANGIOTENSIN SYSTEM AND OXIDATIVE STRESS AND INFLAMMATION TO THE BLOOD PRESSURE CONTROL IN YOUNG SUBJECTS

Kidney Research and Clinical Practice ◽

10.1016/j.krcp.2012.04.542 ◽

2012 ◽

Vol 31 (2) ◽

pp. A72

Author(s):

Emiko Sato ◽

Takefumi Mori ◽

Yoshimi Yoneki ◽

Ikuko Ooba ◽

Mizuho Tanno ◽

...

Keyword(s):

Oxidative Stress ◽

Blood Pressure ◽

Blood Pressure Control ◽

Renin Angiotensin System ◽

Pressure Control ◽

Angiotensin System ◽

Renin Angiotensin ◽

Young Subjects ◽

And Oxidative Stress

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Role of caveolin 1 in AT1a receptor-mediated uptake of angiotensin II in the proximal tubule of the kidney

AJP Renal Physiology ◽

10.1152/ajprenal.00199.2014 ◽

2014 ◽

Vol 307 (8) ◽

pp. F949-F961 ◽

Cited By ~ 14

Author(s):

Xiao C. Li ◽

Victor Gu ◽

Elise Miguel-Qin ◽

Jia L. Zhuo

Keyword(s):

Blood Pressure ◽

Proximal Tubule ◽

Systolic Pressure ◽

Scaffolding Protein ◽

Ang Ii ◽

Caveolin 1 ◽

At1a Receptor ◽

Blood Pressure Responses ◽

Si Rna

Caveolin 1 (CAV-1) functions not only as a constitutive scaffolding protein of caveolae but also as a vesicular transporter and signaling regulator. In the present study, we tested the hypothesis that CAV-1 knockout (CAV-1 KO) inhibits ANG II type 1 [AT1 (AT1a)] receptor-mediated uptake of ANG II in the proximal tubule and attenuates blood pressure responses in ANG II-induced hypertension. To determine the role of CAV-1 in mediating the uptake of FITC-labeled ANG II, wild-type (WT) mouse proximal convoluted tubule cells were transfected with CAV-1 small interfering (si)RNA for 48 h before AT1 receptor-mediated uptake of FITC-labeled ANG II was studied. CAV-1 siRNA knocked down CAV-1 expression by >90% ( P < 0.01) and inhibited FITC-labeled ANG II uptake by >50% ( P < 0.01). Moreover, CAV-1 siRNA attenuated ANG II-induced activation of MAPK ERK1/2 and Na+/H+ exchanger 3 expression, respectively ( P < 0.01). To determine whether CAV-1 regulates ANG II uptake in the proximal tubule, Alexa 488-labeled ANG II was infused into anesthetized WT and CAV-1 KO mice for 60 min (20 ng/min iv). Imaging analysis revealed that Alexa 488-labeled ANG II uptake was decreased by >50% in CAV-1 KO mice ( P < 0.01). Furthermore, Val5-ANG II was infused into WT and CAV-1 KO mice for 2 wk (1.5 mg·kg−1·day−1 ip). Basal systolic pressure was higher, whereas blood pressure and renal excretory and signaling responses to ANG II were attenuated, in CAV-1 KO mice ( P < 0.01). We concluded that CAV-1 plays an important role in AT1 receptor-mediated uptake of ANG II in the proximal tubule and modulates blood pressure and renal responses to ANG II.

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Faculty Opinions recommendation of High-intensity interval training beneficial effects on body mass, blood pressure, and oxidative stress in diet-induced obesity in ovariectomized mice.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.726692682.793522525 ◽

2016 ◽

Author(s):

Jerome Fleg

Keyword(s):

Oxidative Stress ◽

Blood Pressure ◽

High Intensity ◽

Interval Training ◽

High Intensity Interval Training ◽

Beneficial Effects ◽

Diet Induced Obesity ◽

Ovariectomized Mice ◽

High Intensity Interval ◽

And Oxidative Stress

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Inhibition of microRNA-155 Alleviates Neurological Dysfunction Following Transient Global Ischemia and Contribution of Neuroinflammation and Oxidative Stress in the Hippocampus

Current Pharmaceutical Design ◽

10.2174/1381612825666190926162229 ◽

2020 ◽

Vol 25 (40) ◽

pp. 4310-4317 ◽

Cited By ~ 4

Author(s):

Lichao Sun ◽

Shouqin Ji ◽

Jihong Xing

Keyword(s):

Oxidative Stress ◽

Brain Edema ◽

Severity Score ◽

Global Ischemia ◽

Signal Pathways ◽

Neurological Severity Score ◽

Tnf Α ◽

Transient Global Ischemia ◽

And Oxidative Stress

Background/Aims: Central pro-inflammatory cytokine (PIC) signal is involved in neurological deficits after transient global ischemia induced by cardiac arrest (CA). The present study was to examine the role of microRNA- 155 (miR-155) in regulating IL-1β, IL-6 and TNF-α in the hippocampus of rats with induction of CA. We further examined the levels of products of oxidative stress 8-isoprostaglandin F2α (8-iso PGF2α, indication of oxidative stress); and 8-hydroxy-2’-deoxyguanosine (8-OHdG, indication of protein oxidation) after cerebral inhibition of miR-155. Methods: CA was induced by asphyxia and followed by cardiopulmonary resuscitation in rats. ELISA and western blot analysis were used to determine the levels of PICs and products of oxidative stress; and the protein expression of NADPH oxidase (NOXs) in the hippocampus. In addition, neurological severity score and brain edema were examined to assess neurological functions. Results: We observed amplification of IL-1β, IL-6 and TNF-α along with 8-iso PGF2α and 8-OHdG in the hippocampus of CA rats. Cerebral administration of miR-155 inhibitor diminished upregulation of PICs in the hippocampus. This also attenuated products of oxidative stress and upregulation of NOX4. Notably, inhibition of miR-155 improved neurological severity score and brain edema and this was linked to signal pathways of PIC and oxidative stress. Conclusion: We showed the significant role of blocking miR-155 signal in improving the neurological function in CA rats likely via inhibition of signal pathways of neuroinflammation and oxidative stress, suggesting that miR-155 may be a target in preventing and/or alleviating development of the impaired neurological functions during CA-evoked global cerebral ischemia.

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LncRNA SNHG12 Improves Cerebral Ischemic-reperfusion Injury by Activating SIRT1/FOXO3a Pathway through I nhibition of Autophagy and Oxidative Stress

Current Neurovascular Research ◽

10.2174/1567202617666200727142019 ◽

2020 ◽

Vol 17 (4) ◽

pp. 394-401

Author(s):

Yuanhua Wu ◽

Yuan Huang ◽

Jing Cai ◽

Donglan Zhang ◽

Shixi Liu ◽

...

Keyword(s):

Oxidative Stress ◽

Molecular Mechanisms ◽

Ischemia Reperfusion ◽

Critical Role ◽

Cell Activity ◽

Ht22 Cells ◽

Cerebral Ischemic ◽

Cerebral Ischemic Reperfusion ◽

And Oxidative Stress

Background: Ischemia/reperfusion (I/R) injury involves complex biological processes and molecular mechanisms such as autophagy. Oxidative stress plays a critical role in the pathogenesis of I/R injury. LncRNAs are the regulatory factor of cerebral I/R injury. Methods: This study constructs cerebral I/R model to investigate role of autophagy and oxidative stress in cerebral I/R injury and the underline regulatory mechanism of SIRT1/ FOXO3a pathway. In this study, lncRNA SNHG12 and FOXO3a expression was up-regulated and SIRT1 expression was down-regulated in HT22 cells of I/R model. Results: Overexpression of lncRNA SNHG12 significantly increased the cell viability and inhibited cerebral ischemicreperfusion injury induced by I/Rthrough inhibition of autophagy. In addition, the transfected p-SIRT1 significantly suppressed the release of LDH and SOD compared with cells co-transfected with SIRT1 and FOXO3a group and cells induced by I/R and transfected with p-SNHG12 group and overexpression of cells co-transfected with SIRT1 and FOXO3 further decreased the I/R induced release of ROS and MDA. Conclusion: In conclusion, lncRNA SNHG12 increased cell activity and inhibited oxidative stress through inhibition of SIRT1/FOXO3a signaling-mediated autophagy in HT22 cells of I/R model. This study might provide new potential therapeutic targets for further investigating the mechanisms in cerebral I/R injury and provide.

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