scholarly journals Endothelial SHIP2 Suppresses Nox2 NADPH Oxidase–Dependent Vascular Oxidative Stress, Endothelial Dysfunction, and Systemic Insulin Resistance

Diabetes ◽  
2017 ◽  
Vol 66 (11) ◽  
pp. 2808-2821 ◽  
Author(s):  
Nicole T. Watt ◽  
Matthew C. Gage ◽  
Peysh A. Patel ◽  
Hema Viswambharan ◽  
Piruthivi Sukumar ◽  
...  
2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Takehiko Kujiraoka ◽  
Yasushi Satoh ◽  
Makoto Ayaori ◽  
Yasunaga Shiraishi ◽  
Yuko Arai-Nakaya ◽  
...  

Background Insulin signaling comprises 2 major cascades, the IRS/PI3K/Akt and Ras/Raf/MEK/ERK pathways. Many studies on the tissue-specific effects of the former pathway had been conducted, however, the role of the latter cascade in tissue-specific insulin resistance had not been investigated. High glucose/fatty acid toxicity, inflammation and oxidative stress, all of which are associated with insulin resistance, can activate ERK. Liver plays a central role of metabolism and hepatosteatosis (HST) is associated with vascular diseases. The aim of this study is to elucidate the role of hepatic ERK2 in HST, metabolic remodeling and endothelial dysfunction. Methods Serum biomarkers of vascular complications in human were compared between subjects with and without HST diagnosed by echography for regular medical checkup. Next, we created liver-specific ERK2 knockout mice (LE2KO) and fed them with a high-fat/high-sucrose diet (HFHSD) for 20 weeks. The histological analysis, the expression of hepatic sarco/endoplasmic reticulum (ER) Ca 2+ -ATPase 2 (SERCA2) and glucose-tolerance/insulin-sensitivity (GT/IS) were tested. Vascular superoxide production and endothelial function were evaluated with dihydroethidium staining and isometric tension measurement of aorta. Results The presence of HST significantly increased HOMA-IR, an indicator of insulin resistance or atherosclerotic index in human. HFHSD-fed LE2KO revealed a marked exacerbation in HST and metabolic remodeling represented by the impairment of GT/IS, elevated serum free fatty acid and hyperhomocysteinemia without changes in body weight, blood pressure and serum cholesterol/triglyceride levels. In the HFHSD-fed LE2KO, mRNA and protein expressions of hepatic SERCA2 were significantly decreased, which resulted in hepatic ER stress. Induction of vascular superoxide production and remarkable endothelial dysfunction were also observed in them. Conclusions Hepatic ERK2 revealed the suppression of hepatic ER stress and HST in vivo , which resulted in protection from vascular oxidative stress and endothelial dysfunction. HST with hepatic ER stress can be a prominent risk of vascular complications by metabolic remodeling and oxidative stress in obese-related diseases.


2008 ◽  
Vol 53 (6) ◽  
pp. 1272-1281 ◽  
Author(s):  
Delphine Behr-Roussel ◽  
Alexandra Oudot ◽  
Stéphanie Caisey ◽  
Olivier L.E. Coz ◽  
Diane Gorny ◽  
...  

2007 ◽  
Vol 27 (01) ◽  
pp. 5-12 ◽  
Author(s):  
G. Muller ◽  
C. Goettsch ◽  
H. Morawietz

SummaryThis review focuses on the role of vascular oxidative stress in the development and progression of endothelial dysfunction. We discuss different sources of oxidative stress in the vessel wall, oxidative stress and coagulation, the role of oxidative stress and vascular function in arteries and veins, the flow-dependent regulation of reactive oxygen species, the putative impact of oxidative stress on atherosclerosis, the interaction of angiotensin II, oxidative stress and endothelial dysfunction, and clinical implications.


Redox Biology ◽  
2020 ◽  
Vol 28 ◽  
pp. 101330 ◽  
Author(s):  
Mercedes Muñoz ◽  
Maria Elvira López-Oliva ◽  
Claudia Rodríguez ◽  
María Pilar Martínez ◽  
Javier Sáenz-Medina ◽  
...  

2007 ◽  
Vol 46 (6) ◽  
pp. 456-462 ◽  
Author(s):  
Jinah Hwang ◽  
Dean J. Kleinhenz ◽  
Heidi L. Rupnow ◽  
Adam G. Campbell ◽  
Peter M. Thulé ◽  
...  

Heart ◽  
2017 ◽  
Vol 103 (Suppl 5) ◽  
pp. A149.1-A149
Author(s):  
Peysh Patel ◽  
Nicole Watt ◽  
Matthew Gage ◽  
Nadira Yuldasheva ◽  
Hema Viswambharan ◽  
...  

2017 ◽  
Vol 95 (11) ◽  
pp. 1383-1388 ◽  
Author(s):  
Diana Uțu ◽  
Stelian Pantea ◽  
Oana M. Duicu ◽  
Danina M. Muntean ◽  
Adrian Sturza

Arteriovenous fistula (AVF) is the “lifeline” for patients with end-stage renal disease (ESRD) undergoing hemodialysis. AVF maturation failure is a poorly understood process, one of the contributors being endothelial dysfunction due to oxidative stress. Monoamine oxidases (MAOs) A and B were recently identified as novel sources of vascular oxidative stress. The aim of the present study was to assess the contribution of MAOs to the endothelial dysfunction in patients with ESDR with indication of hemodialysis. Fragments of brachial artery collaterals were harvested from ESRD patients during the surgical procedure aimed at creating the vascular access in the cubital fossa. The effect of increasing concentrations (10, 30, 100 μmol/L) of the irreversible MAO-A inhibitor, clorgyline, and MAO-B inhibitor, selegiline, on endothelial-dependent relaxation (EDR) in response to cumulative doses of acetylcholine was studied in isolated phenylephrine-preconstricted vascular rings. Hydrogen peroxide (H2O2) production was assessed using ferrous oxidation xylenol orange assay. We showed that incubation of brachial rings with MAO inhibitors significantly improved EDR and attenuated H2O2 generation in patients with ESRD. MAO-related oxidative stress might contribute to the primary dysfunction/non-maturation of the AVF and MAO inhibitors could improve maturation and long-term patency of the vascular access in dialysis patients.


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