scholarly journals Low-Grade Systemic Inflammation Causes Endothelial Dysfunction in Patients with Hashimoto’s Thyroiditis

2006 ◽  
Vol 91 (12) ◽  
pp. 5076-5082 ◽  
Author(s):  
Stefano Taddei ◽  
Nadia Caraccio ◽  
Agostino Virdis ◽  
Angela Dardano ◽  
Daniele Versari ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Vitamin C ◽  
Systemic Inflammation ◽  
Antioxidant Vitamin ◽  
Low Grade ◽  
Reactive Protein ◽  
Cox 2 ◽  
Oxide Synthase ◽  
Low Grade Inflammation

Abstract Objective: The objective of this study was to assess whether low-grade systemic inflammation might contribute to the pathogenesis of endothelial dysfunction in patients with subclinical hypothyroidism (sHT) and autoimmune thyroiditis. Background: sHT patients are characterized by peripheral endothelial dysfunction and low-grade inflammation. Methods: In 53 sHT and 45 healthy subjects, we studied the forearm blood flow (strain-gauge plethysmography) response to intrabrachial acetylcholine (Ach) (0.15–15 μg/min·dl) with and without local vascular COX inhibition by intrabrachial indomethacin (50 μg/min·dl) or nitric oxide synthase blockade by N-mono methyl arginine (l-NMMA) (100 μg/min·dl) or the antioxidant vitamin C (8 mg/min·dl). The protocol was repeated 2 h after systemic nonselective COX inhibition (100 mg indomethacin) or selective COX-2 blockade (200 mg celecoxib) oral administrations. Results: sHT patients showed higher C-reactive protein and IL-6 values. In controls, vasodilation to Ach was blunted by l-NMMA and unchanged by vitamin C. In contrast, in sHT, the response to Ach, reduced in comparison with controls, was resistant to l-NMMA and normalized by vitamin C. In these patients, systemic but not local indomethacin normalized vasodilation to Ach and the inhibition of l-NMMA on Ach. Similar results were obtained with celecoxib. When retested after indomethacin administration, vitamin C no longer succeeded in improving vasodilation to Ach in sHT patients. Response to sodium nitroprusside was unchanged by indomethacin or celecoxib. Conclusions: In sHT patients, low-grade chronic inflammation causes endothelial dysfunction and impaired nitric oxide availability by a COX-2-dependent pathway leading to increased production of oxidative stress.

Abstract 068: Ghrelin Restores Nitric Oxide Availability In The Forearm Microcirculation Of Essential Hypertensive Patients

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Agostino Virdis ◽  
Emiliano Duranti ◽  
Umberto Dell'Agnello ◽  
Gianni Lorenzini ◽  
Stefano Taddei
Keyword(s):  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Inhibitory Effect ◽  
Antioxidant Vitamin ◽  
Low Grade ◽  
Hypertensive Patients ◽  
Plasma Antioxidant Capacity ◽  
Normotensive Subjects ◽  
Plasma Antioxidant ◽  
Vit C

Objective: Essential hypertensive patients (EH) are characterized by endothelial dysfunction caused by a reduced nitric oxide (NO) availability due to reactive oxygen species excess and low-grade inflammatory condition. Ghrelin is a recently identified growth hormone-releasing peptide, with recognized cardiovascular actions. Possible effects on endothelial dysfunction have been never investigated in EH. In this study we evaluated whether exogenous ghrelin can improve endothelial dysfunction in the forearm microcirculation of untreated mild-moderate EH. Methods: In 9 EH (51.8±8.1 yrs) and 9 normotensive subjects (NS, 50.5±3.5 yrs), we studied the forearm blood flow (FBF, strain-gauge plethysmography) response to intrabrachial acetylcholine (ACh, 0.15-15 mg/100 ml/min) with and without NO synthase blockade by L-NMMA (100 μg/100 ml/min), or the antioxidant vitamin (Vit) C (8 mg/100 ml/min). The protocol was repeated under exogenous ghrelin intra-arterial infusion (200 ng/min, 30’ pre-infusion). Results: In NS, maximal vasodilation (VD) to ACh (480±20%) was inhibited by L-NMMA (292±22, -39±7%; P<0.001) and unchanged by Vit C (482±34%). Ghrelin failed to modify these vascular responses. In EH, VD to ACh was blunted vs NS (337±45%; P<0.001) and resistant to L-NMMA (313±32, -7±3%). Vit C increased the response to ACh (509±57%; P<0.01 vs ACh alone) and restored the inhibiting effect of L-NMMA (332±42, -34±8%; P<0.001). Ghrelin, while not modifying the basal FBF, it increased (P<0.001) the VD to ACh (448±55%) and restored the inhibitory effect of L-NMMA on ACh (355±43, -20±6%; P<0.001). Vit C only slightly improved VD to ACh under ghrelin infusion (486±45%). In EH ghrelin significantly (P<0.05) decreased plasma venous malodialdehyde (from 6.9±1.5 to 5.2±1.0 μmol/L), lipoperoxides (from 9.1±1.9 to 6.6±2.3 μmol/L) and IL-6 (from 11.1±0.6 to 9.3±1.0 pg/mL) and increased plasma antioxidant capacity (from 407±109 to 630±97 mmol/L). Response to sodium nitroprusside was similar between EH and NS and not affected by ghrelin. Conclusions: Exogenous ghrelin is able to ameliorate endothelial dysfunction by restoring NO availability in the forearm microcirculation of EH, an effect probably determined by antioxidant and/or anti-inflammatory activities.

The Inflammation Network in the Pathogenesis of Erectile Dysfunction: Attractive Potential Therapeutic Targets

2020 ◽  
Vol 26 (32) ◽  
pp. 3955-3972
Author(s):  
Ecem Kaya-Sezginer ◽  
Serap Gur
Keyword(s):  
Erectile Dysfunction ◽  
Endothelial Dysfunction ◽  
Metabolic Diseases ◽  
Inflammatory Marker ◽  
Attractive Potential ◽  
Common Denominator ◽  
Low Grade ◽  
Antiinflammatory Drugs ◽  
Male Population ◽  
Low Grade Inflammation

Background: Erectile dysfunction (ED) is an evolving health problem in the aging male population. Chronic low-grade inflammation is a critical component of ED pathogenesis and a probable intermediate stage of endothelial dysfunction, especially in metabolic diseases, with the inclusion of obesity, metabolic syndrome, and diabetes. Objective: This review will present an overview of preclinical and clinical data regarding common inflammatory mechanisms involved in the pathogenesis of ED associated with metabolic diseases and the effect of antiinflammatory drugs on ED. Methods: A literature search of existing pre-clinical and clinical studies was performed on databases [Pubmed (MEDLINE), Scopus, and Embase] from January 2000 to October 2019. Results: Low-grade inflammation is a possible pathological role in endothelial dysfunction as a consequence of ED and other related metabolic diseases. Increased inflammation and endothelial/prothrombotic markers can be associated with the presence and degree of ED. Pharmacological therapy and modification of lifestyle and risk factors may have a significant role in the recovery of erectile response through reduction of inflammatory marker levels. Conclusion: Inflammation is the least common denominator in the pathology of ED and metabolic disorders. The inflammatory process of ED includes a shift in the complex interactions of cytokines, chemokines, and adhesion molecules. These data have established that anti-inflammatory agents could be used as a therapeutic opportunity in the prevention and treatment of ED. Further research on inflammation-related mechanisms underlying ED and the effect of therapeutic strategies aimed at reducing inflammation is required for a better understanding of the pathogenesis and successful management of ED.

scholarly journals Endothelial dysfunction and body mass index: is there a role for plasma peroxynitrite?

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Theresa Chikopela ◽  
Douglas C. Heimburger ◽  
Longa Kaluba ◽  
Pharaoh Hamambulu ◽  
Newton Simfukwe ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Body Mass ◽  
Vascular Function ◽  
Aortic Ring ◽  
Normal Weight ◽  
Oxide Synthase ◽  
Weight Groups

Abstract Background Endothelial function is dependent on the balance between vasoconstrictive and vasodilatory substances. The endothelium ability to produce nitric oxide is one of the most crucial mechanisms in regulating vascular tone. An increase in inducible nitric oxide synthase contributes to endothelial dysfunction in overweight persons, while oxidative stress contributes to the conversion of nitric oxide to peroxynitrite (measured as nitrotyrosine in vivo) in underweight persons. The objective of this study was to elucidate the interaction of body composition and oxidative stress on vascular function and peroxynitrite. This was done through an experimental design with three weight groups (underweight, normal weight and overweight), with four treatment arms in each. Plasma nitrotyrosine levels were measured 15–20 h post lipopolysaccharide (LPS) treatment, as were aortic ring tension changes. Acetylcholine (ACh) and sodium nitroprusside (SNP) challenges were used to observe endothelial-dependent and endothelial-independent vascular relaxation after pre-constriction of aortic rings with phenylephrine. Results Nitrotyrosine levels in saline-treated rats were similar among the weight groups. There was a significant increase in nitrotyrosine levels between saline-treated rats and those treated with the highest lipopolysaccharide doses in each of the weight groups. In response to ACh challenge, Rmax (percentage reduction in aortic tension) was lowest in overweight rats (112%). In response to SNP, there was an insignificantly lower Rmax in the underweight rats (106%) compared to the normal weight rats (112%). Overweight rats had a significant decrease in Rmax (83%) in response to SNP, signifying involvement of a more chronic process in tension reduction changes. A lower Rmax accompanied an increase in peroxynitrite after acetylcholine challenge in all weight groups. Conclusions Endothelial dysfunction, observed as an impairment in the ability to reduce tension, is associated with increased plasma peroxynitrite levels across the spectrum of body mass. In higher-BMI rats, an additional role is played by vascular smooth muscle in the causation of endothelial dysfunction.

scholarly journals Endothelial PPAR-γ provides vascular protection from IL-1β-induced oxidative stress

2016 ◽  
Vol 310 (1) ◽  
pp. H39-H48 ◽  
Author(s):  
Masashi Mukohda ◽  
Madeliene Stump ◽  
Pimonrat Ketsawatsomkron ◽  
Chunyan Hu ◽  
Frederick W. Quelle ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Nitric Oxide Synthase ◽  
Transgenic Mice ◽  
Stress Responses ◽  
Endothelial Nitric Oxide Synthase ◽  
Ppar Γ ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Loss of peroxisome proliferator-activated receptor (PPAR)-γ function in the vascular endothelium enhances atherosclerosis and NF-κB target gene expression in high-fat diet-fed apolipoprotein E-deficient mice. The mechanisms by which endothelial PPAR-γ regulates inflammatory responses and protects against atherosclerosis remain unclear. To assess functional interactions between PPAR-γ and inflammation, we used a model of IL-1β-induced aortic dysfunction in transgenic mice with endothelium-specific overexpression of either wild-type (E-WT) or dominant negative PPAR-γ (E-V290M). IL-1β dose dependently decreased IκB-α, increased phospho-p65, and increased luciferase activity in the aorta of NF-κB-LUC transgenic mice. IL-1β also dose dependently reduced endothelial-dependent relaxation by ACh. The loss of ACh responsiveness was partially improved by pretreatment of the vessels with the PPAR-γ agonist rosiglitazone or in E-WT. Conversely, IL-1β-induced endothelial dysfunction was worsened in the aorta from E-V290M mice. Although IL-1β increased the expression of NF-κB target genes, NF-κB p65 inhibitor did not alleviate endothelial dysfunction induced by IL-1β. Tempol, a SOD mimetic, partially restored ACh responsiveness in the IL-1β-treated aorta. Notably, tempol only modestly improved protection in the E-WT aorta but had an increased protective effect in the E-V290M aorta compared with the aorta from nontransgenic mice, suggesting that PPAR-γ-mediated protection involves antioxidant effects. IL-1β increased ROS and decreased the phospho-endothelial nitric oxide synthase (Ser1177)-to-endothelial nitric oxide synthase ratio in the nontransgenic aorta. These effects were completely abolished in the aorta with endothelial overexpression of WT PPAR-γ but were worsened in the aorta with E-V290M even in the absence of IL-1β. We conclude that PPAR-γ protects against IL-1β-mediated endothelial dysfunction through a reduction of oxidative stress responses but not by blunting IL-1β-mediated NF-κB activity.

scholarly journals Endothelial Dysfunction and Low-Grade Inflammation Are Associated With Greater Arterial Stiffness Over a 6-Year Period

Hypertension ◽  
2011 ◽  
Vol 58 (4) ◽  
pp. 588-595 ◽  
Author(s):  
Bas C. van Bussel ◽  
Fleur Schouten ◽  
Ronald M. Henry ◽  
Casper G. Schalkwijk ◽  
Michiel R. de Boer ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Arterial Stiffness ◽  
Low Grade ◽  
Low Grade Inflammation

Endothelial dysfunction and low-grade inflammation and the progression of retinopathy in Type 2 diabetes

2007 ◽  
Vol 24 (9) ◽  
pp. 969-976 ◽  
Author(s):  
A. M. W. Spijkerman ◽  
M.-A. Gall ◽  
L. Tarnow ◽  
J. W. R. Twisk ◽  
E. Lauritzen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Endothelial Dysfunction ◽  
Low Grade ◽  
Low Grade Inflammation

scholarly journals Potential pitfalls in analyzing structural uncoupling of eNOS: aging is not associated with increased enzyme monomerization

2019 ◽  
Vol 316 (1) ◽  
pp. H80-H88 ◽  
Author(s):  
Fumin Chang ◽  
Sheila Flavahan ◽  
Nicholas A. Flavahan
Keyword(s):  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Nitric Oxide Synthase ◽  
Endothelial Nitric Oxide Synthase ◽  
Normal Activity ◽  
Aortic Endothelial Cells ◽  
Relative Expression ◽  
Fischer 344 ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Homodimer formation is essential for the normal activity of endothelial nitric oxide synthase (eNOS). Structural uncoupling of eNOS, with generation of enzyme monomers, is thought to contribute to endothelial dysfunction in several vascular disorders, including aging. However, low-temperature SDS-PAGE of healthy arteries has revealed considerable variation between studies in the relative expression of eNOS dimers and monomers. While assessing structural uncoupling of eNOS in aging arteries, we identified methodological pitfalls that might contribute to such variation. Therefore, using human cultured aortic endothelial cells and aortas from young and aged Fischer-344 rats, we investigated optimal approaches for analyzing the expression of eNOS monomers and dimers. The results demonstrated that published differences in treatment of cell lysates can significantly impact the relative expression of several eNOS species, including denatured monomers, partially folded monomers, dimers, and higher-order oligomers. In aortas, experiments initially confirmed a large increase in eNOS monomers in aging arteries, consistent with structural uncoupling. However, these monomers were actually endogenous IgG, which, under these conditions, has mobility similar to eNOS monomers. Increased IgG levels in aged aortas likely reflect the aging-induced disruption of endothelial junctions and increased arterial penetration of IgG. After removal of the IgG signal, there were low levels of eNOS monomers in young arteries, which were not significantly different in aged arteries. Therefore, structural uncoupling of eNOS is not a prominent feature in young healthy arteries, and the process is not increased by aging. The study also identifies optimal approaches to analyze eNOS dimers and monomers. NEW & NOTEWORTHY Structural uncoupling of endothelial nitric oxide synthase (eNOS) is considered central to endothelial dysfunction. However, reported levels of eNOS dimers and monomers vary widely, even in healthy arteries. We demonstrate that sample processing can alter relative levels of eNOS species. Moreover, endothelial dysfunction in aging aortas results in IgG accumulation, which, because of similar mobility to eNOS monomers, could be misinterpreted as structural uncoupling. Indeed, enzyme monomerization is not prominent in young or aging arteries.

Sign in / Sign up

Export Citation Format

Share Document