Ginseng in vascular dysfunction: A review of therapeutic potentials and molecular mechanisms

2022 ◽  
Author(s):  
He Zhang ◽  
Cheng Hu ◽  
Jiaojiao Xue ◽  
Di Jin ◽  
Lulu Tian ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Vascular Dysfunction

scholarly journals A systems biology model of junctional localization and downstream signaling of the Ang–Tie signaling pathway

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yu Zhang ◽  
Christopher D. Kontos ◽  
Brian H. Annex ◽  
Aleksander S. Popel
Keyword(s):  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Vascular Dysfunction ◽  
Reaction Network ◽  
Vascular Growth ◽  
Downstream Signaling ◽  
Signaling Axis ◽  
Agonistic Activity ◽  
Molecular Regulatory Mechanisms

AbstractThe Ang–Tie signaling pathway is an important vascular signaling pathway regulating vascular growth and stability. Dysregulation in the pathway is associated with vascular dysfunction and numerous diseases that involve abnormal vascular permeability and endothelial cell inflammation. The understanding of the molecular mechanisms of the Ang–Tie pathway has been limited due to the complex reaction network formed by the ligands, receptors, and molecular regulatory mechanisms. In this study, we developed a mechanistic computational model of the Ang–Tie signaling pathway validated against experimental data. The model captures and reproduces the experimentally observed junctional localization and downstream signaling of the Ang–Tie signaling axis, as well as the time-dependent role of receptor Tie1. The model predicts that Tie1 modulates Tie2’s response to the context-dependent agonist Ang2 by junctional interactions. Furthermore, modulation of Tie1’s junctional localization, inhibition of Tie2 extracellular domain cleavage, and inhibition of VE-PTP are identified as potential molecular strategies for potentiating Ang2’s agonistic activity and rescuing Tie2 signaling in inflammatory endothelial cells.

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 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 New and Old Mechanisms Associated with Hypertension in the Elderly

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Petra J. Mateos-Cáceres ◽  
Jose J. Zamorano-León ◽  
Pablo Rodríguez-Sierra ◽  
Carlos Macaya ◽  
Antonio J. López-Farré
Keyword(s):  
Molecular Mechanisms ◽  
Scientific Literature ◽  
Vascular Dysfunction ◽  
The Elderly ◽  
Hypertension Treatment ◽  
Epigenetic Factors ◽  
Active Metabolites ◽  
Circulating Microparticles ◽  
Cellular Apoptosis ◽  
Different Origin

Hypertension is a widely prevalent and important risk factor for cardiovascular diseases that increase with aging. The hallmark of hypertension in the elderly is increased vascular dysfunction. However, the molecular mechanisms by which increased blood pressure leads to vascular injury and impaired endothelial function are not well defined. In the present paper, we will analyze several mechanisms described in the scientific literature involved in hypertension in the elderly as endothelial dysfunction, increased oxygen delivery to tissues, inflammation, cellular apoptosis, and increased concentration of active metabolites. Also, we will focus on new molecular mechanisms involved in hypertension such as telomeres shortening, progenitor cells, circulating microparticles, and epigenetic factors that have appeared as possible causes of hypertension in the elderly. These molecular mechanisms may elucidate different origin for hypertension in the elderly and provide us with new targets for hypertension treatment.

Vascular injury in diabetic db/db mice is ameliorated by atorvastatin: role of Rac1/2-sensitive Nox-dependent pathways

2014 ◽  
Vol 128 (7) ◽  
pp. 411-423 ◽  
Author(s):  
Thiago Bruder-Nascimento ◽  
Glaucia E. Callera ◽  
Augusto C. Montezano ◽  
Ying He ◽  
Tayze T. Antunes ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Vascular Injury ◽  
Molecular Mechanisms ◽  
Vascular Dysfunction

Our data identify putative molecular mechanisms involving Rac1/2-sensitive, NADPH oxidase (Nox)-dependent pathways, whereby statins may protect against vascular dysfunction in diabetes.

Molecular mechanisms of maternal vascular dysfunction in preeclampsia

2015 ◽  
Vol 21 (2) ◽  
pp. 88-97 ◽  
Author(s):  
Styliani Goulopoulou ◽  
Sandra T. Davidge
Keyword(s):  
Molecular Mechanisms ◽  
Vascular Dysfunction

scholarly journals Advanced in Molecular Mechanisms of Atherosclerosis: From Lipids to Inflammation

2018 ◽  
Vol 10 (2) ◽  
pp. 104-22 ◽  
Author(s):  
Anna Meiliana ◽  
Nurrani Mustika Dewi ◽  
Andi Wijaya
Keyword(s):  
Vascular Disease ◽  
Blood Vessels ◽  
Molecular Mechanisms ◽  
Vascular Dysfunction ◽  
In Vivo Studies ◽  
Disease States ◽  
Fibrous Cap ◽  
Plaque Disruption

BACKGROUND: Atherosclerosis is a leading cause of vascular disease worldwide. During the past several decades, landmark discoveries in the field of vascular biology have evolved our understanding of the biology of blood vessels and the pathobiology of local and systemic vascular disease states and have led to novel disease-modifying therapies for patients. This review is made to understand the molecular mechanism of atherosclerosis for these future therapies.CONTENT: Advances in molecular biology and -omics technologies have facilitated in vitro and in vivo studies which revealed that blood vessels regulate their own redox milieu, metabolism, mechanical environment, and phenotype, in part, through complex interactions between cellular components of the blood vessel wall and circulating factors. Dysregulation of these carefully orchestrated homeostatic interactions has also been implicated as the mechanism by which risk factors for cardiopulmonary vascular disease lead to vascular dysfunction, structural remodeling and, ultimately, adverse clinical events.SUMMARY: Atherosclerosis is a heterogeneous disease, despite a common initiating event of apoB-lipoproteins. Despite of acute thrombotic complications, an adequate resolution response is mounted, where efferocytosis prevents plaque necrosis and a reparative scarring response (the fibrous cap) prevents plaque disruption. However, a small percentage of developing atherosclerotic lesions cannot maintain an adequate resolution response, which leading to the formation of clinically dangerous plaques that can trigger acute lumenal thrombosis and tissue ischemiaand infarction.KEYWORDS: atherosclerosis, oxidative stress, inflammation, efferocytosis, foam cells, thrombosis

Context-Dependent Regulation of Nrf2/ARE Axis on Vascular Cell Function during Hyperglycemic Condition

2020 ◽  
Vol 16 (8) ◽  
pp. 797-806 ◽  
Author(s):  
Tharmarajan Ramprasath ◽  
Allen John Freddy ◽  
Ganesan Velmurugan ◽  
Dhanendra Tomar ◽  
Balakrishnan Rekha ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
High Glucose ◽  
Molecular Mechanisms ◽  
Cell Function ◽  
Vascular Dysfunction ◽  
Redox Balance ◽  
Antioxidant Response ◽  
Antioxidant Genes ◽  
Increased Risk ◽  
Context Dependent

: Diabetes mellitus is associated with an increased risk of micro and macrovascular complications. During hyperglycemic conditions, endothelial cells and vascular smooth muscle cells are exquisitely sensitive to high glucose. This high glucose-induced sustained reactive oxygen species production leads to redox imbalance, which is associated with endothelial dysfunction and vascular wall remodeling. Nrf2, a redox-regulated transcription factor plays a key role in the antioxidant response element (ARE)-mediated expression of antioxidant genes. Although accumulating data indicate the molecular mechanisms underpinning the Nrf2 regulated redox balance, understanding the influence of the Nrf2/ARE axis during hyperglycemic condition on vascular cells is paramount. This review focuses on the context-dependent role of Nrf2/ARE signaling on vascular endothelial and smooth muscle cell function during hyperglycemic conditions. This review also highlights improving the Nrf2 system in vascular tissues, which could be a potential therapeutic strategy for vascular dysfunction.

Abstract P341: Osteoprotegerin-induced ROS Production and Redox Signalling is Exacerbated in Hypertension and Involves Syndecan-1 and TRPM2 Activation

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Augusto C Montezano ◽  
Ross Hepburn ◽  
Delyth Graham ◽  
Rhian M Touyz
Keyword(s):  
Vascular Function ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Vascular Dysfunction ◽  
Ros Generation ◽  
Ros Production ◽  
Redox Signalling ◽  
Wky Rats ◽  
Amplex Red ◽  
Src Activation

Osteoprotegerin (OPG) levels are increased in metabolic diseases, and are a biomarker of vascular dysfunction and cardiovascular risk. Mechanisms related to OPG-induced vascular dysfunction and its role in hypertension are not fully understood, but we previously demonstrated that OPG induces vascular dysfunction through ROS-dependent mechanisms. Here we assessed the molecular mechanisms whereby OPG regulates ROS and vascular function, with a focus on syndecan-1. VSMCs from normotensive (WKY) and hypertensive (SHRSP) rats were stimulated with OPG (50 ng/mL). ROS production was measured by lucigenin, amplex red and ELISA. In VSMCs from WKY rats, OPG increased ROS generation (158±15% vs veh, p<0.05). This effect was blocked by the syndecan-1 inhibitor (synstatin) and by removal of syndecan-1 sulfate proteoglycans side chains, chondroitinase and heparinase. OPG also increased H 2 O 2 (2 fold) and ONOO - (1.5 fold) levels in VSMCs (p<0.05). H 2 O 2 further stimulates ROS levels and redox signalling through activation of TRPM2, a redox-sensitive Ca 2+ channel. TRPM2 inhibitors, 8-bromo-ADPR (8Br) and N-(p-amylcinnamoyl)anthranilic acid (ACA), did not block OPG-induced ROS generation in VSMCs from WKY rats. Syndecan-1 activation leads to FAK and c-Src activation, which are redox-sensitive signalling proteins. FAK, but not c-Src, activation (117±2%, p<0.05) was observed after OPG stimulation of WKY VSMCs. In VSMCS from SHRSP rats, OPG effects on ROS generation were exacerbated (230±40%, p<0.05) and inhibited by synstatin, 8Br and ACA. OPG also increased FAK (118±2) and c-Src (113±1) activation (p<0.05) in VSMCs from SHRSP rats. In conclusion, OPG regulation of oxidative stress is increased in hypertension and involves not only syndecan-1, but also TRPM2 channels, which may lead to activation of redox-sensitive proteins and vascular damage.

scholarly journals 30 YEARS OF THE MINERALOCORTICOID RECEPTOR: The role of the mineralocorticoid receptor in the vasculature

2017 ◽  
Vol 234 (1) ◽  
pp. T67-T82 ◽  
Author(s):  
Jennifer J DuPont ◽  
Iris Z Jaffe
Keyword(s):  
Blood Pressure ◽  
Vascular Function ◽  
Mineralocorticoid Receptor ◽  
Molecular Mechanisms ◽  
Vascular Dysfunction ◽  
Vascular Inflammation ◽  
Kidney Injury ◽  
Vascular Pathology ◽  
The Impact

Since the mineralocorticoid receptor (MR) was cloned 30 years ago, it has become clear that MR is expressed in extra-renal tissues, including the cardiovascular system, where it is expressed in all cells of the vasculature. Understanding the role of MR in the vasculature has been of particular interest as clinical trials show that MR antagonism improves cardiovascular outcomes out of proportion to changes in blood pressure. The last 30 years of research have demonstrated that MR is a functional hormone-activated transcription factor in vascular smooth muscle cells and endothelial cells. This review summarizes advances in our understanding of the role of vascular MR in regulating blood pressure and vascular function, and its contribution to vascular disease. Specifically, vascular MR contributes directly to blood pressure control and to vascular dysfunction and remodeling in response to hypertension, obesity and vascular injury. The literature is summarized with respect to the role of vascular MR in conditions including: pulmonary hypertension; cerebral vascular remodeling and stroke; vascular inflammation, atherosclerosis and myocardial infarction; acute kidney injury; and vascular pathology in the eye. Considerations regarding the impact of age and sex on the function of vascular MR are also described. Further investigation of the precise molecular mechanisms by which MR contributes to these processes will aid in the identification of novel therapeutic targets to reduce cardiovascular disease (CVD)-related morbidity and mortality.

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