New and classical methods to compare oxidative stress levels and parameters of vascular function in rat models of hypertension, diabetes and nitrate tolerance

Essential thrombocythemia (ET) is a BCR-ABL1-negative myeloproliferative neoplasm associated with thrombotic and haemorrhagic complications. Reactive oxygen species (ROS) overexpression induces a growth advantage to JAK2V617F-positive clones and, in association with a higher number of immature platelets, leukocytosis, and additional cardiovascular risk factors, leads to an increased risk for thrombotic events. We evaluated oxidative stress by measuring ROS levels and the total antioxidant capacity (TAC) in 62 ET patients and investigated the relationship between oxidative stress, JAK2V617F mutational status and the development of thrombotic events. We found higher oxidative stress levels in JAK2V617F-positive vs. JAK2V617F-negative ET cases with no significant differences between homozygous and heterozygous genotypes. Increased ROS levels and thrombotic events were more frequent in ET patients with old age at diagnosis, higher haematocrit levels or leukocytosis.

Download Full-text

Coptisine Attenuates Diabetes—Associated Endothelial Dysfunction through Inhibition of Endoplasmic Reticulum Stress and Oxidative Stress

Molecules ◽

10.3390/molecules26144210 ◽

2021 ◽

Vol 26 (14) ◽

pp. 4210

Author(s):

Yan Zhou ◽

Chunxiu Zhou ◽

Xutao Zhang ◽

Chi Teng Vong ◽

Yitao Wang ◽

...

Keyword(s):

Oxidative Stress ◽

Risk Factors ◽

Endoplasmic Reticulum ◽

Er Stress ◽

Vascular Function ◽

Inflammatory Responses ◽

Therapeutic Potential ◽

Ex Vivo ◽

Diabetic Mice ◽

And Oxidative Stress

Coptisine is the major bioactive protoberberine alkaloid found in Rhizoma Coptidis. Coptisine reduces inflammatory responses and improves glucose tolerance; nevertheless, whether coptisine has vasoprotective effect in diabetes is not fully characterized. Conduit arteries including aortas and carotid arteries were obtained from male C57BL/6J mice for ex vivo treatment with risk factors (high glucose or tunicamycin) and coptisine. Some arterial rings were obtained from diabetic mice, which were induced by high-fat diet (45% kcal% fat) feeding for 6 weeks combined with a low-dose intraperitoneal injection of streptozotocin (120 mg/kg). Functional studies showed that coptisine protected endothelium-dependent relaxation in aortas against risk factors and from diabetic mice. Coptisine increased phosphorylations of AMPK and eNOS and downregulated the endoplasmic reticulum (ER) stress markers as determined by Western blotting. Coptisine elevates NO bioavailability and decreases reactive oxygen species level. The results indicate that coptisine improves vascular function in diabetes through suppression of ER stress and oxidative stress, implying the therapeutic potential of coptisine to treat diabetic vasculopathy.

Download Full-text

GLP-1 Analog Liraglutide Improves Vascular Function in Polymicrobial Sepsis by Reduction of Oxidative Stress and Inflammation

Antioxidants ◽

10.3390/antiox10081175 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1175

Author(s):

Johanna Helmstädter ◽

Karin Keppeler ◽

Franziska Aust ◽

Leonie Küster ◽

Katie Frenis ◽

...

Keyword(s):

Oxidative Stress ◽

Vascular Function ◽

Vascular Inflammation ◽

Cecal Ligation ◽

Isometric Tension ◽

Polymicrobial Sepsis ◽

Dot Blot ◽

Markers Of Inflammation ◽

Anti Inflammatory ◽

And Oxidative Stress

Sepsis causes high mortality in the setting of septic shock. LEADER and other trials revealed cardioprotective and anti-inflammatory properties of glucagon-like peptide-1 (GLP-1) analogs like liraglutide (Lira). We previously demonstrated improved survival in lipopolysaccharide (LPS)-induced endotoxemia by inhibition of GLP-1 degradation. Here we investigate the effects of Lira in the polymicrobial sepsis model of cecal ligation and puncture (CLP). C57BL/6J mice were intraperitoneally injected with Lira (200 µg/kg/d; 3 days) and sepsis induced by CLP after one day of GLP-1 analog treatment. Survival and body temperature were monitored. Aortic vascular function (isometric tension recording), protein expression (immunohistochemistry and dot blot) and gene expression (qRT-PCR) were determined. Endothelium-dependent relaxation in the aorta was impaired by CLP and correlated with markers of inflammation (e.g., interleukin 6 and inducible nitric oxide synthase) and oxidative stress (e.g., 3-nitrotyrosine) was higher in septic mice, all of which was almost completely normalized by Lira therapy. We demonstrate that the GLP-1 analog Lira ameliorates sepsis-induced endothelial dysfunction by the reduction of vascular inflammation and oxidative stress. Accordingly, the findings suggest that the antioxidant and anti-inflammatory effects of GLP-1 analogs may be a valuable tool to protect the cardiovascular system from dysbalanced inflammation in polymicrobial sepsis.

Download Full-text

Effects of heat-not-burn compared to combustible cigarettes on coronary flow, myocardial work index and vascular function

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jeaa356.098 ◽

2021 ◽

Vol 22 (Supplement_1) ◽

Author(s):

I Ikonomidis ◽

K Katogiannis ◽

D Vlastos ◽

G Kostelli ◽

K Kourea ◽

...

Keyword(s):

Oxidative Stress ◽

Platelet Activation ◽

Vascular Function ◽

Coronary Flow ◽

Arterial Compliance ◽

Chronic Phase ◽

Protein Carbonyls ◽

Flow Reserve ◽

Work Index ◽

Chronic Study

Abstract Funding Acknowledgements Type of funding sources: None. Aim/Introduction: Heat-not-burn cigarette (HNBC) constitutes a non-combustible smoke product. Purpose We compare the effects of heat-not-burn and conventional cigarettes on coronary flow, myocardial and vascular function, platelet activation and oxidative stress. Methods We compared the effects of HNBC to those of tobacco cigarette (TCig), on arterial stiffness, oxidative stress, and platelet activation, acutely and after 1 month of switching to HNBC, as well as on endothelial, myocardial, and coronary function after 1 month of switching to HNBC. In the acute study, 50 smokers were randomized into smoking a single Tcig or an HNBC and after 60 minutes were crossed over to the alternate smoking (HNBC or Tcig). For the chronic phase, 75 smokers were examined. Of those, 50 were switched to HNBC and 25 continued Tcig for 1 month. Pulse wave velocity (PWV) and biomarkers [malondialdehyde (MDA), protein carbonyls (PC), and thromboxane B2 (TXB2)] were assessed in the acute and chronic study. Myocardial deformation [global longitundinal strain (GLS), myocardial work index (GWI) and wasted myocardial work (GWW)], coronary flow reserve (CFR) by Doppler echocardiography, total arterial compliance (TAC), and flow-mediated dilation (FMD) were additionally assessed in the chronic study. Results Compared to baseline, TCig smoking acutely increased exhaled CO, PWV, MDA, and TxB2 (p < 0.05), while no changes were observed after HNBC. Compared to resuming Tcig smoking, switching to HNBC for 1 month improved CO (mean change: -55% vs -2.4%), FMD ( +55% vs +15%), CFR (+46% vs +4%), TAC (+9% vs -0.5%), GLS (+6% vs +1%), GWW (-19% vs +0.5%), MDA (-19% vs 1 %), and TxB2 (-12% vs 4%) (p < 0.05 for all comparisons). Conclusions HNBCs exert a less detrimental effect on vascular, cardiac and platelet function than combustible tobacco.

Download Full-text

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

Beni-Suef University Journal of Basic and Applied Sciences ◽

10.1186/s43088-020-00092-6 ◽

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.

Download Full-text

Age-Related Macular Degeneration: Role of Oxidative Stress and Blood Vessels

International Journal of Molecular Sciences ◽

10.3390/ijms22031296 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1296

Author(s):

Yue Ruan ◽

Subao Jiang ◽

Adrian Gericke

Keyword(s):

Oxidative Stress ◽

Macular Degeneration ◽

Vascular Function ◽

Vascular Dysfunction ◽

Therapeutic Strategies ◽

Vision Impairment ◽

Age Related Macular Degeneration ◽

Oxygen Species ◽

Age Related

Age-related macular degeneration (AMD) is a common irreversible ocular disease characterized by vision impairment among older people. Many risk factors are related to AMD and interact with each other in its pathogenesis. Notably, oxidative stress and choroidal vascular dysfunction were suggested to be critically involved in AMD pathogenesis. In this review, we give an overview on the factors contributing to the pathophysiology of this multifactorial disease and discuss the role of reactive oxygen species and vascular function in more detail. Moreover, we give an overview on therapeutic strategies for patients suffering from AMD.

Download Full-text

Nitric oxide synthase 3 deficiency limits adverse ventricular remodeling after pressure overload in insulin resistance

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00744.2010 ◽

2011 ◽

Vol 301 (5) ◽

pp. H2093-H2101 ◽

Cited By ~ 5

Author(s):

Baptiste Kurtz ◽

Helene B. Thibault ◽

Michael J. Raher ◽

John R. Popovich ◽

Sharon Cawley ◽

...

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Insulin Resistance ◽

Mitochondrial Respiration ◽

Pressure Overload ◽

Lv Remodeling ◽

Stress Levels ◽

Nitric Oxide Synthase 3 ◽

And Function ◽

Oxide Synthase

Insulin resistance (IR) and systemic hypertension are independently associated with heart failure. We reported previously that nitric oxide synthase 3 (NOS3) has a beneficial effect on left ventricular (LV) remodeling and function after pressure-overload in mice. The aim of our study was to investigate the interaction of IR and NOS3 in pressure-overload-induced LV remodeling and dysfunction. Wild-type (WT) and NOS3-deficient (NOS3−/−) mice were fed either a standard diet (SD) or a high-fat diet (HFD) to induce IR. After 9 days of diet, mice underwent transverse aortic constriction (TAC). LV structure and function were assessed serially using echocardiography. Cardiomyocytes were isolated, and levels of oxidative stress were evaluated using 2′,7′-dichlorodihydrofluorescein diacetate. Cardiac mitochondria were isolated, and mitochondrial respiration and ATP production were measured. TAC induced LV remodeling and dysfunction in all mice. The TAC-induced decrease in LV function was greater in SD-fed NOS3−/− mice than in SD-fed WT mice. In contrast, HFD-fed NOS3−/− developed less LV remodeling and dysfunction and had better survival than did HFD-fed WT mice. Seven days after TAC, oxidative stress levels were lower in cardiomyocytes from HFD-fed NOS3−/− than in those from HFD-fed WT. Nω-nitro-l-arginine methyl ester and mitochondrial inhibitors (rotenone and 2-thenoyltrifluoroacetone) decreased oxidative stress levels in cardiomyocytes from HFD-fed WT mice. Mitochondrial respiration was altered in NOS3−/− mice but did not worsen after HFD and TAC. In contrast with its protective role in SD, NOS3 increases LV adverse remodeling after pressure overload in HFD-fed, insulin resistant mice. Interactions between NOS3 and mitochondria may be responsible for increased oxidative stress levels in HFD-fed WT mice hearts.

Download Full-text