scholarly journals Roles of Inflammation, Oxidative Stress, and Vascular Dysfunction in Hypertension

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Quynh N. Dinh ◽  
Grant R. Drummond ◽  
Christopher G. Sobey ◽  
Sophocles Chrissobolis
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Potential Benefit ◽  
Animal Studies ◽  
Vascular Dysfunction ◽  
Inflammatory Cascade ◽  
Inflammatory Drugs ◽  
Sympathetic Nervous ◽  
Anti Inflammatory ◽  
Key Steps

Hypertension is a complex condition and is the most common cardiovascular risk factor, contributing to widespread morbidity and mortality. Approximately 90% of hypertension cases are classified as essential hypertension, where the precise cause is unknown. Hypertension is associated with inflammation; however, whether inflammation is a cause or effect of hypertension is not well understood. The purpose of this review is to describe evidence from human and animal studies that inflammation leads to the development of hypertension, as well as the evidence for involvement of oxidative stress and endothelial dysfunction—both thought to be key steps in the development of hypertension. Other potential proinflammatory conditions that contribute to hypertension—such as activation of the sympathetic nervous system, aging, and elevated aldosterone—are also discussed. Finally, we consider the potential benefit of anti-inflammatory drugs and statins for antihypertensive therapy. The evidence reviewed suggests that inflammation can lead to the development of hypertension and that oxidative stress and endothelial dysfunction are involved in the inflammatory cascade. Aging and aldosterone may also both be involved in inflammation and hypertension. Hence, in the absence of serious side effects, anti-inflammatory drugs could potentially be used to treat hypertension in the future.

scholarly journals A Review on the Effects of Melatonin on Fetal Protection during Pregnancy with Intrauterine Inflammation

2020 ◽  
Vol 24 (4) ◽  
pp. 196-203
Author(s):  
Jang Mee Kim ◽  
Ji Yeon Lee
Keyword(s):  
Oxidative Stress ◽  
Pregnant Women ◽  
Animal Studies ◽  
Protective Effects ◽  
Fetal Protection ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
The Brain ◽  
Fetal Inflammatory Response

Intrauterine inflammation is defined as the inflammation of the chorion, amnion, and placenta. Untreated inflammation increases the risk of fetal inflammatory response syndrome, which may result in multiorgan diseases involving the brain, cardiovascular system, lung, eye, and intestine. Therefore, controlling inflammation is critical in pregnant women to reduce the risk of diseases. However, there are no safe and effective anti-inflammatory drugs for administration during pregnancy. Although the primary function of melatonin is to control circadian rhythms, it has protective effects against cellular insults occurring from hypoxia, oxidative stress, and inflammation. While animal studies support the effective and safe role of melatonin in improving pregnancy-related morbidities, it leaves plenty of opportunities for clinical studies investigating its anti-inflammatory, antioxidant, and protective effects against insults induced by intrauterine inflammation. Therefore, it will be worthwhile to investigate antenatal supplementation of melatonin in pregnant women with intrauterine inflammation to reduce the incidence of associated comorbidities.

Abstract MP30: Circulating Sars-cov-2 Spike Protein 1 Causes Microarteriolar Oxidative Stress, Endothelial Dysfunction And Enhanced Thromboxane And Endothelin Contractility That Are Prevented By Spironolactone.

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Dan Wang ◽  
Christopher S Wilcox
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
Fluorescence Microscopy ◽  
Vascular Dysfunction ◽  
Microvascular Complications ◽  
Spike Protein ◽  
Ros Generation ◽  
Intravenous Injections ◽  
Novel Model

Introduction and hypothesis: Following bodily entry, the SARS-CoV-2 virus undergoes pulmonary replication with release of circulating viral spike protein 1 (SP1) into the bloodstream. Uptake of SP1 by endothelial cells might provoke vascular dysfunction and thrombosis. We hypothesized that spironolactone could prevent microvascular complications from circulating SP1 in COVID-19. Methods: male C57Bl/6 mice received spironolactone (100 mg · kg -1 · d -1 PO x 3d) or vehicle and intravenous injections of recombinant full-length human SP1 (10 μg per mouse) or vehicle. They were euthanized after 3 days. Mesenteric resistant arterioles (n=4 per group) were dissected and mounted on isometric myographs. Acetylcholine-induced EDRF responses and L-NAME-inhibitable NO generation (DAF-FM fluorescence) were studied in pre-constricted vessels and contraction to endothelin 1 (ET1) or thromboxane (U-46, 619) and ET1-induced ROS (PEG-SOD inhibitable ethidium: dihydroethidium fluorescence) were studied by fluorescence microscopy in other vessels. Results: SP1 reduced acetylcholine-induced EDRF (17 ± 3 vs 27 ± 5 % mean ± sem; P < 0.05) and NO generation (0.21 ± 0.03 vs 0.36 ± 0.04, F 1 /F 0 ; P < 0.05) while increasing contraction to ET1 (10 -7 mol·l -1 : 124 ± 13 vs 89 ± 4 %; P < 0.05) and U-46, 619 (10 -6 mol·l -1 :114± 5 vs 87± 6 %; P < 0.05) and ET1-induced ROS generation(0.30± 0.08 vs 0.09± 0.03; P < 0.05). Spironolactone did not modify any of these responses in vessels from normal mice but prevented all the effects of SP1. Conclusion: these preliminary studies provide a novel model to study COVID-19 vasculopathy. They indicate that spironolactone can provide protection from microvascular oxidative stress, endothelial dysfunction and enhanced contractility and might thereby moderate COVID-19 complications.

scholarly journals Kidney dysfunction in the low-birth weight murine adult: implications of oxidative stress

2018 ◽  
Vol 315 (3) ◽  
pp. F583-F594 ◽  
Author(s):  
Wasan Abdulmahdi ◽  
May M. Rabadi ◽  
Edson Jules ◽  
Yara Marghani ◽  
Noor Marji ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Birth Weight ◽  
Endothelial Dysfunction ◽  
Low Birth Weight ◽  
Vascular Dysfunction ◽  
Vascular Density ◽  
Immunofluorescence Analysis ◽  
Doppler Flowmetry ◽  
Maternal Undernutrition ◽  
Nephron Endowment

Maternal undernutrition (MUN) during pregnancy leads to low-birth weight (LBW) neonates that have a reduced kidney nephron endowment and higher morbidity as adults. Using a severe combined caloric and protein-restricted mouse model of MUN to generate LBW mice, we examined the progression of renal insufficiency in LBW adults. Through 6 mo of age, LBW males experienced greater albuminuria (ELISA analysis), a more rapid onset of glomerular hypertrophy, and a worse survival rate than LBW females. In contrast, both sexes experienced a comparable progressive decline in renal vascular density (immunofluorescence analysis), renal blood flow (Laser-Doppler flowmetry analysis), glomerular filtration rate (FITC-sinistrin clearance analysis), and a progressive increase in systemic blood pressure (measured via tail-cuff method). Isolated aortas from both LBW sexes demonstrated reduced vasodilation in response to ACh, indicative of reduced nitric oxide bioavailability and endothelial dysfunction. ELISA and immunofluorescence analysis revealed a significant increase of circulating reactive oxygen species and NADPH oxidase type 4 (NOX4) expression in both LBW sexes, although these increases were more pronounced in males. Although more effective in males, chronic tempol treatment did improve all observed pathologies in both sexes of LBW mice. Chronic NOX4 inhibition with GKT137831 was more effective than tempol in preventing pathologies in LBW males. In conclusion, despite some minor differences, LBW female and male adults have a reduced nephron endowment comparable with progressive renal and vascular dysfunction, which is associated with increased oxidative stress and subsequent endothelial dysfunction. Tempol treatment and/or NOX4 inhibition attenuates renal and vascular dysfunction in LBW adults.

scholarly journals Recent Advances in Liposomal-Based Anti-Inflammatory Therapy

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1004
Author(s):  
Carla van Alem ◽  
Josbert Metselaar ◽  
Cees van Kooten ◽  
Joris Rotmans
Keyword(s):  
Animal Studies ◽  
Inflammatory Diseases ◽  
Vascular Inflammation ◽  
Systemic Exposure ◽  
Target Cells ◽  
Liposomal Formulations ◽  
Current Review ◽  
Target Sites ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

Liposomes can be seen as ideal carriers for anti-inflammatory drugs as their ability to (passively) target sites of inflammation and release their content to inflammatory target cells enables them to increase local efficacy with only limited systemic exposure and adverse effects. Nonetheless, few liposomal formulations seem to reach the clinic. The current review provides an overview of the more recent innovations in liposomal treatment of rheumatoid arthritis, psoriasis, vascular inflammation, and transplantation. Cutting edge developments include the liposomal delivery of gene and RNA therapeutics and the use of hybrid systems where several liposomal bilayer features, or several drugs, are combined in a single formulation. The majority of the articles reviewed here focus on preclinical animal studies where proof-of-principle of an improved efficacy–safety ratio is observed when using liposomal formulations. A few clinical studies are included as well, which brings us to a discussion about the challenges of clinical translation of liposomal nanomedicines in the field of inflammatory diseases.

Differential effects of non-steroidal anti-inflammatory drugs on mitochondrial dysfunction during oxidative stress

2009 ◽  
Vol 490 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Nirupama Lal ◽  
Jitendra Kumar ◽  
Warren E. Erdahl ◽  
Douglas R. Pfeiffer ◽  
Martha. E. Gadd ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Differential Effects ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

Protective Effects of Pomegranate in Endothelial Dysfunction

2020 ◽  
Vol 26 (30) ◽  
pp. 3684-3699 ◽  
Author(s):  
Nathalie T.B. Delgado ◽  
Wender N. Rouver ◽  
Roger L. dos Santos
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Diseases ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Common Factor ◽  
Blood Lipid ◽  
Punica Granatum ◽  
Protective Effects ◽  
Beneficial Effects ◽  
Anti Inflammatory

Background: Punica granatum L. is an infructescence native of occidental Asia and Mediterranean Europe, popularly referred to as pomegranate. It has been used in ethnomedicine for several applications, including the treatment of obesity, inflammation, diabetes, and the regulation of blood lipid parameters. Thus, pomegranate has been linked to the treatment of cardiovascular diseases that have endothelial dysfunction as a common factor acting mainly against oxidative stress due to its high polyphenol content. Its biocomponents have antihypertensive, antiatherogenic, antihyperglycemic, and anti-inflammatory properties, which promote cardiovascular protection through the improvement of endothelial function. Methods: Different electronic databases were searched in a non-systematic way to uncover the literature of interest. Conclusion: This review article presents updated information on the role of pomegranate in the context of endothelial dysfunction and cardiovascular diseases. We have shown that pomegranate, or rather its components (e.g., tannins, flavonoids, phytoestrogens, anthocyanins, alkaloids, etc.), have beneficial effects on the cardiovascular system, improving parameters such as oxidative stress and the enzymatic antioxidant system, reducing reactive oxygen species formation and acting in an anti-inflammatory way. Thus, this review may contribute to a better understanding of pomegranate's beneficial actions on endothelial function and possibly to the development of strategies associated with conventional treatments of cardiovascular diseases.

Evaluation of Therapeutic Effects of Quercetin Against Achilles Tendinopathy in Rats via Oxidative Stress, Inflammation, Apoptosis, Autophagy, and Metalloproteinases

2021 ◽  
pp. 036354652110598
Author(s):  
Halil Sezgin Semis ◽  
Cihan Gur ◽  
Mustafa Ileriturk ◽  
Fatih Mehmet Kandemir ◽  
Ozgur Kaynar
Keyword(s):  
Oxidative Stress ◽  
Achilles Tendinopathy ◽  
Therapeutic Effects ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Alternative Treatment Option ◽  
Markers Of Oxidative Stress ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
The One

Background: Achilles tendinopathy, seen in athletes and manual labor workers, is an inflammatory condition characterized by chronic tendon pain. Owing to the toxicity that develops in various organs attributed to the use of anti–inflammatory drugs, there is a need for new therapeutic agents. Purpose: In the present study, the effects of quercetin (Que), the one that attracted the most attention of researchers studying this group of flavonoids, were investigated against collagenase–induced tendinopathy. Study Design: Controlled laboratory study. Methods: A total of 35 Sprague-Dawley rats were used in the study. Tendinopathy was created by injecting a single dose of collagenase (10 μL; 10 mg/mL) into the tendons of rats. Thirty minutes after the injection, Que was administered at doses of 25 or 50 mg/kg. Que administration was carried out for 7 days. Animals underwent a motility test at the end of the study. In addition, markers of oxidative stress, inflammation, apoptosis, and autophagy, as well as the expression levels of matrix metalloproteinases (MMPs 2, 3, 9, and 13), ICAM-1, and STAT3, were measured in tendon tissues with biochemical, molecular, and Western blot techniques. Results: The results showed that oxidative stress, inflammation, apoptosis, and autophagy were triggered by the injection of collagenase. In addition, MMPs, ICAM-1, and STAT3 were activated to participate in the development of tendinopathy. Que was found to reduce ICAM-1 levels in tendon tissue. Moreover, Que showed antioxidant, anti–inflammatory, antiapoptotic, and antiautophagic effects on tendons against tendinopathy. More important, Que suppressed the expression of MMPs in the tendon tissues. Conclusion: Que has protective properties against collagenase–induced tendon damage in rats. Clinical Relevance: We believe that with further study, Que may be shown to be an alternative treatment option for athletes or others who experience tendon injuries.

Abstract 14746: Dynamic SIRTUIN1-modulated Lysine Acetylation of P66shc Governs Vascular Endothelial Oxidative Stress and Dysfunction of Diabetes

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Santosh Kumar ◽  
Young Rae Kim ◽  
Ajit Vikram ◽  
Asma Naqvi ◽  
Ajay Kumar ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
High Glucose ◽  
Vascular Dysfunction ◽  
Stress Protein ◽  
Lysine Acetylation ◽  
Vascular Endothelial ◽  
Endothelium Dysfunction ◽  
Lysine Deacetylase ◽  
Oxidative Function

The SIRTUIN1 lysine deacetylase (SIRT1) ameliorates diabetic vascular dysfunction by epigenetically suppressing endothelial expression of the oxidative stress protein p66shc. However, whether SIRT1 modulates the oxidative function of p66shc by directly targeting it for lysine deacetylation is not known. Here we show that the oxidative function of p66shc is dynamically modulated by lysine acetylation. Mass spectroscopy identified lysine 81 in the unique CH2 domain of p66shc as the residue targeted by SIRT1. High glucose and SIRT1 knockdown stimulates acetylation of lysine 81 of endothelial p66shc. Compared to WT p66shc, non-acetylatable (K81R) p66shc is significantly handicapped in promoting endothelial hydrogen peroxide production stimulated by high glucose. Compared to WT p66shc, K81R p66shc is also less prone to serine 36 phosphorylation by high glucose, which is essential for the oxidative function of p66shc. Moreover, in contrast to WT p66shc which worsens endothelial dysfunction, expression of K81R p66shc does not impair endothelial function in wild type mice and rescues endothelium dysfunction of diabetic db+/db+ mouse aortas . These findings show that lysine 81 acetylation promotes the oxidative role of p66shc in hyperglycemic conditions, and is essential for p66shc-mediated endothelial dysfunction.

scholarly journals Suppression of Tumor Angiogenesis by Nonsteroidal Anti-Inflammatory Drugs: A New Function for Old Drugs

2001 ◽  
Vol 1 ◽  
pp. 808-811 ◽  
Author(s):  
Curzio Raegg ◽  
Olivier Dormond
Keyword(s):  
Tumor Angiogenesis ◽  
Animal Studies ◽  
Tumor Formation ◽  
Polyposis Coli ◽  
Epidemiological Evidence ◽  
Familial Adenomatous Polyposis Coli ◽  
Clinical Observations ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Old Drugs

There is solid epidemiological evidence demonstrating that the regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) reduces the risk of developing colorectal cancer, and to a lesser extent gastric and esophageal cancers[1]. Importantly, NSAIDs suppress colon polyp formation and progression in patients diagnosed with familial adenomatous polyposis coli (APC)[2]. In many animal studies, NSAIDs have been shown to prevent tumor formation and slow tumor progression, thus confirming and extending the clinical observations[3,4,5]. Recent findings have demonstrated that NSAIDs inhibit angiogenesis, suggesting that the tumor suppressive activity of these drugs may be due, at least in part, to their ability to inhibit tumor angiogenesis[6]. The study of the mechanism by which NSAIDs suppress tumor angiogenesis, is matter of intense research.

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