scholarly journals Vascular Dysfunction in Preeclampsia

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3055
Author(s):  
Megan A. Opichka ◽  
Matthew W. Rappelt ◽  
David D. Gutterman ◽  
Justin L. Grobe ◽  
Jennifer J. McIntosh
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Vascular Dysfunction ◽  
Treatment Options ◽  
Cardiovascular Disorder ◽  
Endothelial Damage ◽  
Spiral Artery ◽  
Mitochondrial Stress ◽  
Inflammatory State ◽  
Life Threatening

Preeclampsia is a life-threatening pregnancy-associated cardiovascular disorder characterized by hypertension and proteinuria at 20 weeks of gestation. Though its exact underlying cause is not precisely defined and likely heterogenous, a plethora of research indicates that in some women with preeclampsia, both maternal and placental vascular dysfunction plays a role in the pathogenesis and can persist into the postpartum period. Potential abnormalities include impaired placentation, incomplete spiral artery remodeling, and endothelial damage, which are further propagated by immune factors, mitochondrial stress, and an imbalance of pro- and antiangiogenic substances. While the field has progressed, current gaps in knowledge include detailed initial molecular mechanisms and effective treatment options. Newfound evidence indicates that vasopressin is an early mediator and biomarker of the disorder, and promising future therapeutic avenues include mitigating mitochondrial dysfunction, excess oxidative stress, and the resulting inflammatory state. In this review, we provide a detailed overview of vascular defects present during preeclampsia and connect well-established notions to newer discoveries at the molecular, cellular, and whole-organism levels.

scholarly journals Could metabolomics drive the fate of COVID-19 pandemic? A narrative review on lights and shadows

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Michele Mussap ◽  
Vassilios Fanos
Keyword(s):  
Molecular Mechanisms ◽  
Vascular Dysfunction ◽  
Asymptomatic Infection ◽  
Multiple Organ ◽  
Therapeutic Interventions ◽  
Patient Specific ◽  
Wide Range ◽  
Life Threatening ◽  
The Individual ◽  
Host Metabolism

Abstract Human Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection activates a complex interaction host/virus, leading to the reprogramming of the host metabolism aimed at the energy supply for viral replication. Alterations of the host metabolic homeostasis strongly influence the immune response to SARS-CoV-2, forming the basis of a wide range of outcomes, from the asymptomatic infection to the onset of COVID-19 and up to life-threatening acute respiratory distress syndrome, vascular dysfunction, multiple organ failure, and death. Deciphering the molecular mechanisms associated with the individual susceptibility to SARS-CoV-2 infection calls for a system biology approach; this strategy can address multiple goals, including which patients will respond effectively to the therapeutic treatment. The power of metabolomics lies in the ability to recognize endogenous and exogenous metabolites within a biological sample, measuring their concentration, and identifying perturbations of biochemical pathways associated with qualitative and quantitative metabolic changes. Over the last year, a limited number of metabolomics- and lipidomics-based clinical studies in COVID-19 patients have been published and are discussed in this review. Remarkable alterations in the lipid and amino acid metabolism depict the molecular phenotype of subjects infected by SARS-CoV-2; notably, structural and functional data on the lipids-virus interaction may open new perspectives on targeted therapeutic interventions. Several limitations affect most metabolomics-based studies, slowing the routine application of metabolomics. However, moving metabolomics from bench to bedside cannot imply the mere determination of a given metabolite panel; rather, slotting metabolomics into clinical practice requires the conversion of metabolic patient-specific data into actionable clinical applications.

scholarly journals Inhibition of Protein Kinase Cβ Does Not Improve Endothelial Function in Type 2 Diabetes

2010 ◽  
Vol 95 (8) ◽  
pp. 3783-3787 ◽  
Author(s):  
Joshua A. Beckman ◽  
Allison B. Goldfine ◽  
Alison Goldin ◽  
Adnan Prsic ◽  
Sora Kim ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Type 2 Diabetes ◽  
Healthy Subjects ◽  
Vascular Dysfunction ◽  
Endothelial Damage ◽  
Markers Of Inflammation ◽  
Resistance Vessels ◽  
Healthy Control ◽  
And Oxidative Stress

Context: Antagonism of protein kinase Cβ (PKCβ) restores endothelial function in experimental models of diabetes and prevents vascular dysfunction in response to hyperglycemia in healthy humans. Objective: We tested the hypothesis that PKCβ antagonism would improve vascular function in subjects with type 2 diabetes compared with healthy control subjects. Design: The effect of PKCβ was evaluated in a randomized, placebo-controlled, double-blinded crossover trial. Setting: The study was performed in the outpatient setting of a university medical center. Participants: Thirteen subjects with type 2 diabetes without evidence of cardiovascular disease and 15 healthy control subjects were recruited via newspaper advertisement. Intervention: Subjects underwent a randomized, double-blind, crossover, placebo-controlled trial of the selective PKCβ antagonist ruboxistaurin mesylate. Subjects received each treatment for 14 d. Main Outcome Measure: Endothelium-dependent and endothelium-independent vasodilation of forearm resistance vessels was measured with mercury-in-silastic, strain-gauge plethysmography during intraarterial administration of methacholine chloride and verapamil, respectively. Markers of inflammation, fibrinolysis, endothelial damage, and oxidative stress were measured after each treatment. Results: Endothelium-dependent vasodilation of forearm resistance vessels was attenuated in diabetic subjects when compared with healthy subjects (P = 0.001). Endothelium-independent vasodilation did not differ between groups (P value not significant). Ruboxistaurin did not significantly change endothelium-dependent or endothelium-independent vasodilation or blood-based markers of inflammation, fibrinolysis, endothelial damage, and oxidative stress in either diabetic or healthy subjects. Conclusion: Endothelial dysfunction of forearm resistance vessels was not improved by 2 wk of selective PKCβ inhibition in patients with diabetes. These results suggest that PKCβ does not contribute significantly to vascular dysfunction in otherwise healthy patients with type 2 diabetes.

scholarly journals The effects of real and simulated microgravity on cellular mitochondrial function

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Hong Phuong Nguyen ◽  
Phuong Hoa Tran ◽  
Kyu-Sung Kim ◽  
Su-Geun Yang
Keyword(s):  
Oxidative Stress ◽  
Respiratory Chain ◽  
Metabolic Pathways ◽  
Molecular Mechanisms ◽  
Simulated Microgravity ◽  
Space Shuttle ◽  
Parabolic Flight ◽  
Space Station ◽  
Microgravity Environment ◽  
Mitochondrial Stress

AbstractAstronauts returning from space shuttle missions or the International Space Station have been diagnosed with various health problems such as bone demineralization, muscle atrophy, cardiovascular deconditioning, and vestibular and sensory imbalance including visual acuity, altered metabolic and nutritional status, and immune system dysregulation. These health issues are associated with oxidative stress caused by a microgravity environment. Mitochondria are a source of reactive oxygen species (ROS). However, the molecular mechanisms through which mitochondria produce ROS in a microgravity environment remain unclear. Therefore, this review aimed to explore the mechanism through which microgravity induces oxidative damage in mitochondria by evaluating the expression of genes and proteins, as well as relevant metabolic pathways. In general, microgravity-induced ROS reduce mitochondrial volume by mainly affecting the efficiency of the respiratory chain and metabolic pathways. The impaired respiratory chain is thought to generate ROS through premature electron leakage in the electron transport chain. The imbalance between ROS production and antioxidant defense in mitochondria is the main cause of mitochondrial stress and damage, which leads to mitochondrial dysfunction. Moreover, we discuss the effects of antioxidants against oxidative stress caused by the microgravity environment space microgravity in together with simulated microgravity (i.e., spaceflight or ground-based spaceflight analogs: parabolic flight, centrifugal force, drop towers, etc.). Further studies should be taken to explore the effects of microgravity on mitochondrial stress-related diseases, especially for the development of new therapeutic drugs that can help increase the health of astronauts on long space missions.

scholarly journals Oxidative stress and endoplasmic reticulum (ER) stress in the development of neonatal hypoxic–ischaemic brain injury

2017 ◽  
Vol 45 (5) ◽  
pp. 1067-1076 ◽  
Author(s):  
Claire Thornton ◽  
Ana A. Baburamani ◽  
Anton Kichev ◽  
Henrik Hagberg
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Brain Injury ◽  
Molecular Mechanisms ◽  
Treatment Options ◽  
Neuronal Cell Death ◽  
Birth Asphyxia ◽  
Neuronal Cell ◽  
Term Neonates ◽  
Ischaemic Brain

Birth asphyxia in term neonates affects 1–2/1000 live births and results in the development of hypoxic–ischaemic encephalopathy with devastating life-long consequences. The majority of neuronal cell death occurs with a delay, providing the potential of a treatment window within which to act. Currently, treatment options are limited to therapeutic hypothermia which is not universally successful. To identify new interventions, we need to understand the molecular mechanisms underlying the injury. Here, we provide an overview of the contribution of both oxidative stress and endoplasmic reticulum stress in the development of neonatal brain injury and identify current preclinical therapeutic strategies.

scholarly journals The Role of Na/K-ATPase Signaling in Oxidative Stress Related to Aging: Implications in Obesity and Cardiovascular Disease

2018 ◽  
Vol 19 (7) ◽  
pp. 2139 ◽  
Author(s):  
David Bartlett ◽  
Richard Miller ◽  
Scott Thiesfeldt ◽  
Hari Lakhani ◽  
Joseph Shapiro ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Disease ◽  
Patient Outcomes ◽  
Molecular Mechanisms ◽  
Treatment Options ◽  
Cellular Mechanisms ◽  
General Decline ◽  
Pumping Function ◽  
Improve Patient

Aging has been associated with a series of pathophysiological processes causing general decline in the overall health of the afflicted population. The cumulative line of evidence suggests an important role of oxidative stress in the development and progression of the aging process and metabolic abnormalities, exacerbating adipocyte dysfunction, cardiovascular diseases, and associated complications at the same time. In recent years, robust have established the implication of Na/K-ATPase signaling in causing oxidative stress and alterations in cellular mechanisms, in addition to its distinct pumping function. Understanding the underlying molecular mechanisms and exploring the possible sources of pro-oxidants may allow for developing therapeutic targets in these processes and formulate novel intervention strategies for patients susceptible to aging and associated complications, such as obesity and cardiovascular disease. The attenuation of oxidative stress with targeted treatment options can improve patient outcomes and significantly reduce economic burden.

scholarly journals Nitric Oxide, Oxidative Stress, andp66ShcInterplay in Diabetic Endothelial Dysfunction

2014 ◽  
Vol 2014 ◽  
pp. 1-16 ◽  
Author(s):  
Alessandra Magenta ◽  
Simona Greco ◽  
Maurizio C. Capogrossi ◽  
Carlo Gaetano ◽  
Fabio Martelli
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Molecular Mechanisms ◽  
Vascular Dysfunction ◽  
Diabetic Patients ◽  
Oxygen Species ◽  
Complex Interplay ◽  
Cell Dysfunction ◽  
Intracellular Ros ◽  
No Bioavailability

Increased oxidative stress and reduced nitric oxide (NO) bioavailability play a causal role in endothelial cell dysfunction occurring in the vasculature of diabetic patients. In this review, we summarized the molecular mechanisms underpinning diabetic endothelial and vascular dysfunction. In particular, we focused our attention on the complex interplay existing among NO, reactive oxygen species (ROS), and one crucial regulator of intracellular ROS production,p66Shcprotein.

Abstract P097: Molecular Mechanisms of VEGFR Inhibition-induced Endothelial Cell Damage

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Francisco J Rios ◽  
Augusto C Montezano ◽  
Lucas Van Der Mey ◽  
Heather Y Small ◽  
Carmine Savoia ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Mrna Expression ◽  
Vascular Function ◽  
Molecular Mechanisms ◽  
Cell Damage ◽  
Vascular Dysfunction ◽  
Endothelial Damage ◽  
Mrna Levels ◽  
Ang Ii ◽  
Vegf Inhibitors

VEGF/VEGFR inhibitors, used as anti-angiogenic drugs to treat cancer, induce severe hypertension. Molecular mechanisms whereby VEGF inhibitors cause hypertension are unclear, but nitric oxide (NO) and oxidative stress may be involved. We questioned whether reactive oxygen species (ROS) and Ang II, important regulators of vascular function in hypertension, also play a role in VEGF inhibitor-induced vascular dysfunction. Human microvascular endothelial cells (HMECs) were stimulated with vatalanib (VAT-VEGFR inhibitor) and gefitinib (GEF-EGFR inhibitor) in the absence/presence of Ang II. Activation of eNOS and MAPKs were assessed by immunoblotting. Antioxidant enzyme mRNA was analysed by qPCR. Microparticle levels were measured by flow cytometry. Endothelial microparticles, biomarkers of endothelial damage, tend to increase in subjects treated with VEGFR inhibitors. Phosphorylation of eNOS activation site (Ser1177) (28.3% ± 7.1) was decreased by VAT, while no changes were observed after exposure of HMECs to GEF (p<0.05). VAT decreased mRNA expression of Nox4 (0.5 ± 0.2) and H2O2-regulating antioxidants enzymes such as catalase (0.4 ± 0.1) and glutathione peroxidase (0.4 ± 0.1), while increased mRNA levels of Nox5 (3.35±1.1) (p<0.05 vs. veh). Ang II stimulation increased eNOS (171.2% ± 17.4) and ERK1/2 (177.5% ± 38.5) activation (p<0.05); all effects were blocked only by GEF. Inhibition of VEGFR also blocked Ang II effects on SOD1 (1.33 ± 0.1), HO-1 (1.6 ± 0.3) and NQO1 (1.6 ± 0.3) mRNA levels (p<0.05). In addition, Ang II increased Nox4 mRNA expression through VEGFR-dependent mechanisms. VEGFR1/2 and AT2R, but not AT1R, were expressed in HMEC. Ang II effects on eNOS phosphorylation were inhibited by PD123319 (AT2R antagonist) but not by losartan (AT1R antagonist). In conclusion, our data identify novel mechanisms whereby AngII, possibly through AT2R-dependent VEGFR transactivation, regulates eNOS activation, MAPK signalling and H2O2-related antioxidant enzymes. In addition to changes in NO availability, VEGFR inhibition may interfere with the redox status of endothelial cells, leading to vascular dysfunction and hypertension.

scholarly journals Noise-Induced Vascular Dysfunction, Oxidative Stress, and Inflammation Are Improved by Pharmacological Modulation of the NRF2/HO-1 Axis

Antioxidants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 625
Author(s):  
Maria Teresa Bayo Jimenez ◽  
Katie Frenis ◽  
Swenja Kröller-Schön ◽  
Marin Kuntic ◽  
Paul Stamm ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Sound Pressure Level ◽  
Vascular Function ◽  
Sound Pressure ◽  
Molecular Mechanisms ◽  
Noise Exposure ◽  
Vascular Dysfunction ◽  
Pressure Level ◽  
Aircraft Noise ◽  
Heme Oxygenase 1

Vascular oxidative stress, inflammation, and subsequent endothelial dysfunction are consequences of traditional cardiovascular risk factors, all of which contribute to cardiovascular disease. Environmental stressors, such as traffic noise and air pollution, may also facilitate the development and progression of cardiovascular and metabolic diseases. In our previous studies, we investigated the influence of aircraft noise exposure on molecular mechanisms, identifying oxidative stress and inflammation as central players in mediating vascular function. The present study investigates the role of heme oxygenase-1 (HO-1) as an antioxidant response preventing vascular consequences following exposure to aircraft noise. C57BL/6J mice were treated with the HO-1 inducer hemin (25 mg/kg i.p.) or the NRF2 activator dimethyl fumarate (DMF, 20 mg/kg p.o.). During therapy, the animals were exposed to noise at a maximum sound pressure level of 85 dB(A) and a mean sound pressure level of 72 dB(A). Our data showed a marked protective effect of both treatments on animals exposed to noise for 4 days by normalization of arterial hypertension and vascular dysfunction in the noise-exposed groups. We observed a partial normalization of noise-triggered oxidative stress and inflammation by hemin and DMF therapy, which was associated with HO-1 induction. The present study identifies possible new targets for the mitigation of the adverse health effects caused by environmental noise exposure. Since natural dietary constituents can achieve HO-1 and NRF2 induction, these pathways represent promising targets for preventive measures.

scholarly journals Molecular and Clinical Aspects of Chronic Manifestations in Chagas Disease: A State-of-the-Art Review

Pathogens ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1493
Author(s):  
Germán J. Medina-Rincón ◽  
Sebastián Gallo-Bernal ◽  
Paula A. Jiménez ◽  
Lissa Cruz-Saavedra ◽  
Juan David Ramírez ◽  
...  
Keyword(s):  
Chagas Disease ◽  
Molecular Mechanisms ◽  
Treatment Options ◽  
Diagnosis And Treatment ◽  
Clinical Aspects ◽  
Chronic Complications ◽  
Life Threatening ◽  
Host Parasite ◽  
Prompt Diagnosis ◽  
Disease Present

Chronic manifestations of Chagas disease present as disabling and life-threatening conditions affecting mainly the cardiovascular and gastrointestinal systems. Although meaningful research has outlined the different molecular mechanisms underlying Trypanosoma cruzi’s infection and the host-parasite interactions that follow, prompt diagnosis and treatment remain a challenge, particularly in developing countries and also in those where the disease is considered non-endemic. This review intends to present an up-to-date review of the parasite’s life cycle, genetic diversity, virulence factors, and infective mechanisms, as well as the epidemiology, clinical presentation, diagnosis, and treatment options of the main chronic complications of Chagas disease.

scholarly journals Oxidative Stress, Mitochondrial Function and Adaptation to Exercise: New Perspectives in Nutrition

Life ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1269
Author(s):  
Nancy Vargas-Mendoza ◽  
Marcelo Angeles-Valencia ◽  
Ángel Morales-González ◽  
Eduardo Osiris Madrigal-Santillán ◽  
Mauricio Morales-Martínez ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Free Radicals ◽  
Molecular Mechanisms ◽  
Nuclear Genome ◽  
Oxygen Species ◽  
Mitochondrial Stress ◽  
Stressful Environments ◽  
Mitochondrial Adaptation ◽  
Adaptation To Exercise

Cells have the ability to adapt to stressful environments as a part of their evolution. Physical exercise induces an increase of a demand for energy that must be met by mitochondria as the main (ATP) provider. However, this process leads to the increase of free radicals and the so-called reactive oxygen species (ROS), which are necessary for the maintenance of cell signaling and homeostasis. In addition, mitochondrial biogenesis is influenced by exercise in continuous crosstalk between the mitochondria and the nuclear genome. Excessive workloads may induce severe mitochondrial stress, resulting in oxidative damage. In this regard, the objective of this work was to provide a general overview of the molecular mechanisms involved in mitochondrial adaptation during exercise and to understand if some nutrients such as antioxidants may be implicated in blunt adaptation and/or an impact on the performance of exercise by different means.

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