scholarly journals Red Blood Cell Peroxynitrite Causes Endothelial Dysfunction in Type 2 Diabetes Mellitus via Arginase

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1712 ◽  
Author(s):  
Ali Mahdi ◽  
John Tengbom ◽  
Michael Alvarsson ◽  
Bernhard Wernly ◽  
Zhichao Zhou ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Arginase Activity ◽  
Oxygen Species ◽  
Wild Type ◽  
Arginase I

We recently showed that red blood cells (RBCs) from patients with type 2 diabetes mellitus (T2DM-RBCs) induce endothelial dysfunction through a mechanism involving arginase I and reactive oxygen species. Peroxynitrite is known to activate arginase in endothelial cells. Whether peroxynitrite regulates arginase activity in RBCs, and whether it is involved in the cross-talk between RBCs and the vasculature in T2DM, is unclear and elusive. The present study was designed to test the hypothesis that endothelial dysfunction induced by T2DM-RBCs is driven by peroxynitrite and upregulation of arginase. RBCs were isolated from patients with T2DM and healthy age matched controls. RBCs were co-incubated with aortae isolated from wild type rats for 18 h in the absence and presence of peroxynitrite scavenger FeTTPS. Evaluation of endothelial function in organ chambers by cumulative addition of acetylcholine as well as measurement of RBC and vessel arginase activity was performed. In another set of experiments, RBCs isolated from healthy subjects (Healthy RBCs) were incubated with the peroxynitrite donor SIN-1 with subsequent evaluation of endothelial function and arginase activity. T2DM-RBCs, but not Healthy RBCs, induced impairment in endothelial function, which was fully reversed by scavenging of RBC but not vascular peroxynitrite with FeTPPS. Arginase activity was up-regulated by the peroxynitrite donor SIN-1 in Healthy RBCs, an effect that was inhibited by FeTTPS. Healthy RBCs co-incubated with aortae in the presence of SIN-1 caused impairment of endothelial function, which was inhibited by FeTTPS or the arginase inhibitor ABH. T2DM-RBCs induced up-regulation of vascular arginase, an effect that was fully inhibited by FeTTPS. Collectively, our data indicate that RBCs impair endothelial function in T2DM via an effect that is driven by a peroxynitrite-mediated increase in arginase activity. This mechanism may be targeted in patients with T2DM for improvement in endothelial function.

scholarly journals The Ratio of Oxidized Lipoprotein(a) to Native Lipoprotein(a) and the Endothelial Function in Patients with Type 2 Diabetes Mellitus

2019 ◽  
Vol 20 (19) ◽  
pp. 4909 ◽  
Author(s):  
Kazuhiko Kotani ◽  
Shingo Yamada ◽  
Hirokazu Takahashi ◽  
Yoshitaka Iwazu ◽  
Toshiyuki Yamada
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Enzyme Linked Immunosorbent Assay ◽  
Lipoprotein A ◽  
Oxidized Lipoprotein ◽  
The Mean

The ratio of oxidized lipoprotein(a) to native lipoprotein(a) (oxLp(a)/Lp(a)) may be a reasonable index for assessing endothelial dysfunction in type 2 diabetes mellitus (T2DM). The present study investigated whether the oxLp(a)/Lp(a) level is correlated with the endothelial function using the Endo-PATTM, a newly developed device, in patients with T2DM. A total of 63 patients with T2DM (mean age: 59 years old) were enrolled in the study. The patients’ serum Lp(a) and oxLp(a) levels were measured using an enzyme-linked immunosorbent assay. The reactive hyperemia index (RHI) level was measured using an Endo-PATTM 2000. A correlation analysis between the measured variables was conducted. Among the patients, the mean hemoglobin A1c was 7.8%. The median level of oxLp(a)/Lp(a) was 0.28 (interquartile range: 0.07–0.54), and the mean RHI was 1.8 (standard deviation: 0.4). In a multiple linear regression analysis, the oxLp(a)/Lp(a) level was an independent, significant, and inverse variable for the RHI level (β = −0.26, p < 0.05), along with male gender. A high oxLp(a)/Lp(a) level may reflect endothelial dysfunction, as assessed by the Endo-PATTM, in patients with T2DM. Further studies are warranted to confirm the observed findings.

scholarly journals GLP-1 Agonists Liraglutide Improved Vascular Endothelial Function in Type 2 Diabetes Rats

2020 ◽  
Vol 2 (2) ◽  
pp. 46-55
Author(s):  
Li X ◽  
Wu W ◽  
Wang Y ◽  
Zhang X ◽  
Feng X ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Mesenteric Arteries ◽  
Vascular Endothelial ◽  
Vascular Endothelial Dysfunction ◽  
Vascular Endothelial Function

Objective: Liraglutide (LIRA), a Glucagon-like peptide-1 (GLP-1) receptor agonist, showed potential vascular protective effects with the mechanism remained incompletely understood. Therefore, this study aimed to investigate whether LIRA exerts its effect on vascular endothelial function in rats with type 2 diabetes mellitus (T2DM) via caveolin-1/ endothelial oxide synthase (eNOS) expression. Methods: T2DM rats were used as study subjects and randomly divided into four groups: 1) Veh group, 2) Veh+LIRA group, 3) T2DM group, and 4) T2DM+LIRA group. All rats received either saline or LIRA 0.2 mg/kg (by i.p. injection) per day for 4 weeks. After the model was successfully established, vascular endothelial function was determined the effect of vasodilator to mesenteric artery rings. Immunofluorescence and western blot were performed to understand the molecular mechanism. Cultured HUVECs with small interfering RNA (siRNA) under high glucose (HG), NO concentration, and western blot were performed to understand the molecular mechanism between LIRA and vascular endothelial function. Results: Based on our results, the LIRA reduced hyperglycemia and ameliorated vascular endothelial dysfunction in type 2 diabetic mice. LIRA activated eNOS phosphorylation, suppressing oxidative stress and enhancing endothelium-dependent vasorelaxation of mesenteric arteries. Besides, from its anti-oxidative capacity, LIRA activated eNOS to dilate the mesenteric arteries via the downregulation of Cav-1. Conclusion: LIRA ameliorates vascular endothelial dysfunction in rats with type 2 diabetes mellitus via anti-oxidative and activated eNOS by downregulated Cav-1.

scholarly journals EFFECT OF HIGH-INTENSITY EXERCISE ON ENDOTHELIAL FUNCTION IN PATIENTS WITH T2DM

2016 ◽  
Vol 22 (2) ◽  
pp. 126-130 ◽  
Author(s):  
Carlos Alberto da Silva ◽  
Francisco Sérgio Lopes Vasconcelos-Filho ◽  
Marcus Serafim ◽  
Edson Botura ◽  
Roberta Cristina da Rocha-e-Silva ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Type 2 Diabetes Mellitus ◽  
Endothelial Dysfunction ◽  
Physical Exercise ◽  
Endothelial Function ◽  
High Intensity ◽  
Before And After

Introduction: Diabetes mellitus is the most common metabolic disease worldwide. Endothelial dysfunction characteristic of these patients is one of the major risk factors for atherosclerosis. Early diagnosis of endothelial dysfunction is essential for the treatment especially of non-invasive manner, such as flow mediated dilation. Physical exercise is capable of generating beneficial adaptations may improve endothelial function. Objective: Identify the effect of physical exercise, using the clinical technique of ultrasound in the assessment of the endothelial function of patients with metabolic syndrome or type 2 diabetes mellitus. Methods: Thirty-one patients with type 2 diabetes mellitus or metabolic syndrome were studied, with a mean age (± SD) of 58±6 years, randomized into three groups. The training was performed for 50 minutes, four times a week. Before and after six weeks of training, subjects performed the endurance test and a study of the endothelial function of the brachial artery by high-resolution ultrasound. Results: After hyperemia, the percentage of arterial diameter was significantly higher for the high-intensity group (HI before = 2.52±2.85mm and after = 31.81±12.21mm; LI before = 3.23±3.52mm and after = 20.61±7.76mm; controls before = 3.56±2.33mm and after = 2.43±2.14mm; p<0.05). Conclusions: The high-intensity aerobic training improved the vasodilatation response-dependent endothelium, recorded by ultrasound, in patients with metabolic syndrome and type 2 diabetes.

scholarly journals Endothelial dysfunction and arterial wall stiffness: New targets in diabetic nephropathy

2017 ◽  
Vol 89 (10) ◽  
pp. 87-94
Author(s):  
I T Murkamilov ◽  
I S Sabirov ◽  
V V Fomin ◽  
F A Yusupov
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Type 2 Diabetes Mellitus ◽  
Endothelial Dysfunction ◽  
Kidney Disease ◽  
Endothelial Function ◽  
Arterial Wall ◽  
Wall Stiffness

In recent years, one of the promising areas in clinical medicine is the study of impaired ments in endothelial function and arterial wall stiffness, which can be referred to as one of the important predictors of cardiovascular events in patients with chronic kidney disease, including that of diabetic etiology. There is strong evidence that endothelial function and great artery stiffness may be used as reliable clinical and instrumental indicators to evaluate the efficiency of therapeutic measures and the rate of progression of cardiovascular disorders in type 2 diabetes mellitus. The article presents data on the role of endothelial dysfunction and arterial wall stiffness in the progression of chronic kidney disease in type 2 diabetes mellitus and discusses the possibility of their correction with pharmacological agents.

Role of Vitamin C in Endothelial Dysfunction in Patients with Type 2 Diabetes Mellitus Introduction

2020 ◽  
Vol 11 (2) ◽  
pp. 1701
Author(s):  
Nermien Abd El Rahman Ibraheim ◽  
Fatema El Zahraa Sayed Bukhary ◽  
Yehia Zakareia Mahmoud ◽  
Mahmoud Ragab Mohamed ◽  
Salama Rabei Abdel-Rahim
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Endothelial Dysfunction ◽  
Vitamin C

scholarly journals GTP Cyclohydrolase I Gene Polymorphisms Are Associated with Endothelial Dysfunction and Oxidative Stress in Patients with Type 2 Diabetes Mellitus

PLoS ONE ◽  
2014 ◽  
Vol 9 (11) ◽  
pp. e108587 ◽  
Author(s):  
Pawel P. Wolkow ◽  
Wladyslaw Kosiniak-Kamysz ◽  
Grzegorz Osmenda ◽  
Grzegorz Wilk ◽  
Beata Bujak-Gizycka ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Endothelial Dysfunction ◽  
Gene Polymorphisms ◽  
Gtp Cyclohydrolase I ◽  
And Oxidative Stress ◽  
I Gene
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