Abstract 519: Endothelin-1-Induced Oxidative Stress and Inflammatory Cell Infiltration Play a Role in High-Fat Diet Induced-Atherosclerosis in Apolipoprotein E Knockout Mice

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Melissa W Li ◽  
Pierre Paradis ◽  
Ernesto L Schiffrin
Keyword(s):  
Oxidative Stress ◽  
T Cell ◽  
Apolipoprotein E ◽  
High Fat Diet ◽  
Cell Infiltration ◽  
Ros Production ◽  
High Fat ◽  
T Cell Infiltration ◽  
Atherosclerotic Lesions ◽  
Perivascular Fat

Background: Endothelin (ET)-1 plays an important role in generation of reactive oxygen species (ROS) and inflammation in the vasculature. ET-1has been implicated in the pathogenesis of atherosclerosis since plasma and tissue ET-1 are increased in human and animal models of atherosclerosis. We observed that ET-1 overexpression exacerbates high-fat diet (HFD)-induced atherosclerosis in apolipoprotein E knockout ( apoE -/- ) mice. We hypothesized that ET-1-induced ROS and inflammation contribute to the development of atherosclerosis. Design and methods: Eight-week-old male transgenic mice overexpressing preproET-1 in the endothelium (eET-1), apoE -/- , eET-1/ apoE -/- and wild type mice were fed a HFD for 8 weeks. Aortic atherosclerotic lesions were quantified using Oil Red O staining. ROS production using dihydroethidium staining and monocyte/macrophage and T cell infiltration using immunofluorescence with MOMA-2 and anti-CD4 antibodies, respectively, were determined in perivascular fat, media and plaque in ascending aortic sections. Results: eET-1/ apoE -/- presented 3.8-fold more atherosclerotic lesions in whole aorta compared to apoE -/- ( P <0.01). ET-1 overexpression caused 2.6-, 1.9- and 1.9-fold increase in ROS production in perivascular fat, media and plaque of apoE -/- , respectively ( P <0.05). ET-1 overexpression increased monocyte/macrophage infiltration by 5- and 8-fold in perivascular fat and media, respectively ( P <0.05). CD4 + T cell infiltration was observed in perivascular fat and plaque of 3 and 5 of 6 eET-1/ apoE -/- compared to 0 and 1 of 6 apoE -/- , respectively ( P <0.05). Conclusions: These results suggest that ET-1 play an important role in progression of atherosclerotic lesions by increasing the oxidative stress and monocyte/macrophage and T cell infiltration in the atherosclerotic aorta, including the perivascular fat.

scholarly journals Endothelium-restricted endothelin-1 overexpression in type 1 diabetes worsens atherosclerosis and immune cell infiltration via NOX1

2020 ◽  
Author(s):  
Sofiane Ouerd ◽  
Noureddine Idris-Khodja ◽  
Michelle Trindade ◽  
Nathanne S Ferreira ◽  
Olga Berillo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Type 1 Diabetes ◽  
T Cell ◽  
Aortic Arch ◽  
Vascular Complications ◽  
Cell Infiltration ◽  
Aortic Sinus ◽  
T Cell Infiltration ◽  
Perivascular Fat

Abstract Aims NADPH oxidase (NOX) 1 but not NOX4-dependent oxidative stress plays a role in diabetic vascular disease, including atherosclerosis. Endothelin (ET)-1 has been implicated in diabetes-induced vascular complications. We showed that crossing mice overexpressing human ET-1 selectively in endothelium (eET-1) with apolipoprotein E knockout (Apoe−/−) mice enhanced high-fat diet-induced atherosclerosis in part by increasing oxidative stress. We tested the hypothesis that ET-1 overexpression in the endothelium would worsen atherosclerosis in type 1 diabetes through a mechanism involving NOX1 but not NOX4. Methods and results Six-week-old male Apoe−/− and eET-1/Apoe−/− mice with or without Nox1 (Nox1−/y) or Nox4 knockout (Nox4−/−) were injected intraperitoneally with either vehicle or streptozotocin (55 mg/kg/day) for 5 days to induce type 1 diabetes and were studied 14 weeks later. ET-1 overexpression increased 2.5-fold and five-fold the atherosclerotic lesion area in the aortic sinus and arch of diabetic Apoe−/− mice, respectively. Deletion of Nox1 reduced aortic arch plaque size by 60%; in contrast, Nox4 knockout increased lesion size by 1.5-fold. ET-1 overexpression decreased aortic sinus and arch plaque alpha smooth muscle cell content by ∼35% and ∼50%, respectively, which was blunted by Nox1 but not Nox4 knockout. Reactive oxygen species production was increased two-fold in aortic arch perivascular fat of diabetic eET-1/Apoe−/− and eET-1/Apoe−/−/Nox4−/− mice but not eET-1/Apoe−/−/Nox1y/− mice. ET-1 overexpression enhanced monocyte/macrophage and CD3+ T-cell infiltration ∼2.7-fold in the aortic arch perivascular fat of diabetic Apoe−/− mice. Both Nox1 and Nox4 knockout blunted CD3+ T-cell infiltration whereas only Nox1 knockout prevented the monocyte/macrophage infiltration in diabetic eET-1/Apoe−/− mice. Conclusion Endothelium ET-1 overexpression enhances the progression of atherosclerosis in type 1 diabetes, perivascular oxidative stress, and inflammation through NOX1.

scholarly journals Renal oxidative stress and renal CD8+ T-cell infiltration in mercuric chloride-induced nephropathy in rats: role of angiotensin II

2015 ◽  
Vol 13 (3) ◽  
pp. 324-334 ◽  
Author(s):  
Caterina Peña ◽  
Juan P. Hernández-Fonseca ◽  
Adriana Pedreañez ◽  
Ninoska Viera ◽  
Jesús Mosquera
Keyword(s):  
Oxidative Stress ◽  
T Cell ◽  
Angiotensin Ii ◽  
Mercuric Chloride ◽  
Cd8 T Cell ◽  
Cell Infiltration ◽  
T Cell Infiltration

scholarly journals The Impact of High-Fat Diet on Mitochondrial Function, Free Radical Production, and Nitrosative Stress in the Salivary Glands of Wistar Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Anna Zalewska ◽  
Dominika Ziembicka ◽  
Małgorzata Żendzian-Piotrowska ◽  
Mateusz Maciejczyk
Keyword(s):  
Oxidative Stress ◽  
Free Radical ◽  
High Fat Diet ◽  
Wistar Rats ◽  
Nitrosative Stress ◽  
Ros Production ◽  
Parotid Glands ◽  
High Fat ◽  
Free Radical Production ◽  
Radical Production

Oxidative stress plays a crucial role in the salivary gland dysfunction in insulin resistance; however, the cause of increased free radical formation in these conditions is still unknown. Therefore, the aim of the study was to investigate the effect of high-fat diet (HFD) on the mitochondrial respiratory system, prooxidant enzymes, ROS production, and nitrosative/oxidative stress in the submandibular and parotid glands of rats. The experiment was performed on male Wistar rats divided into two groups (n=10): control and HFD. The 8-week feeding of HFD affects glucose metabolism observed as significant increase in plasma glucose and insulin as well as HOMA-IR as compared to the control rats. The activity of mitochondrial Complex I and Complex II+III was significantly decreased in the parotid and submandibular glands of HFD rats. Mitochondrial cytochrome c oxidase (COX) activity and the hydrogen peroxide level were significantly increased in the parotid and submandibular glands of the HFD group as compared to those of the controls. HFD rats also showed significantly lower reduced glutathione (GSH) and reduced : oxidized glutathione (GSH : GSSG) ratio, as well as a higher GSSG level in the parotid glands of HFD rats. The activity of NADPH oxidase, xanthine oxidase, and levels of oxidative/nitrosative stress (malonaldehyde, nitric oxide, nitrotyrosine, and peroxynitrite) and inflammation/apoptosis (interleukin-1βand caspase-3) biomarkers were statistically elevated in the HFD group in comparison to the controls. HFD impairs mitochondrial function in both types of salivary glands by enhancing ROS production, as well as stimulating inflammation and apoptosis. However, free radical production, protein nitration, and lipid peroxidation were more pronounced in the parotid glands of HFD rats.

Increased atherosclerotic lesions and Th17 in interleukin-18 deficient apolipoprotein E-knockout mice fed high-fat diet

2009 ◽  
Vol 47 (1) ◽  
pp. 37-45 ◽  
Author(s):  
Nada Pejnovic ◽  
Athanassios Vratimos ◽  
Sang Hee Lee ◽  
Dusan Popadic ◽  
Kiyoshi Takeda ◽  
...  
Keyword(s):  
Apolipoprotein E ◽  
Knockout Mice ◽  
High Fat Diet ◽  
Interleukin 18 ◽  
High Fat ◽  
Atherosclerotic Lesions ◽  
Apolipoprotein E Knockout Mice

Abstract 325: Dissociation of Oxidative Stress from High Fatty Acid-Induced Cardiac Myocyte Death

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Nicolas Gutierrez Cortes ◽  
Huiliang Zhang ◽  
Shangcheng Xu ◽  
Guohua Gong ◽  
Wang Wang
Keyword(s):  
Oxidative Stress ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Cardiac Myocytes ◽  
Mitochondrial Respiration ◽  
High Fat Diet ◽  
High Fatty Acid ◽  
Ros Production ◽  
High Fat ◽  
Heart Dysfunction

Metabolic syndrome, featured by obesity and diabetes, is an independent risk factor for cardiovascular disease. The high availability of free fatty acids characteristic of obesity has been proposed to increase fatty acid oxidation, impair mitochondrial function, stimulate reactive oxygen species (ROS) production and eventually lead to oxidative stress, which then would cause myocyte damage and heart dysfunction. However, the role of oxidative stress as the initial cause of obesity-induced heart failure is controversial. We evaluated the time-dependent effect of fatty acids in vitro in adult rat cardiac myocytes (treated with palmitate and oleate, the major saturated and unsaturated fatty acids in the plasma, respectively), and in vivo in mice fed a high-fat diet (fat calories = 60%). Palmitate and oleate dose-dependently stimulated mitochondrial respiration and superoxide flash activity, a respiration-coupled bursting ROS production event in single mitochondria. The flash frequency increased 2-fold (0.1 mM, the physiological level in plasma) and 3-fold (0.3 mM, the plasma level found in obese subjects) after only 2 hr incubation and up to 24 hr, increase that could be blocked by the CPT1 inhibitor etomoxir (100uM). Surprisingly, there was no obvious mitochondrial oxidative stress, although the high level of fatty acids caused mPTP opening and cell death at 48 hr. Further, aconitase activity was normal and NAD/NADH ratio was decreased, indicating a more reduced status rather than oxidative stress. Intriguingly, mitochondrial membrane potential was slightly lowered after only 2 hr of treatment. Finally, the high-fat diet-fed mice developed heart dysfunction after 12 weeks of treatment, but oxidative stress only appeared after 18 weeks. In the light of these results, we hypothesize that high fatty acid supply induced multiple adaptive and mal-adaptive responses in cardiac myocytes. The increased mitochondrial respiration and bursting ROS production is offset by a mild uncoupling and increased reducing equivalents. Therefore, oxidative stress is unlikely an initial cause of myocyte death and heart dysfunction in obesity, but rather a consequence of mitochondrial dysfunction, although the exact cause of this dysfunction remains to be elucidated.

scholarly journals DJ‐1 protects against renal mitochondrial oxidative stress and T cell infiltration

2018 ◽  
Vol 32 (S1) ◽  
Author(s):  
Carmen De Miguel ◽  
William C. Hamrick ◽  
Laureano Assico ◽  
Pedro A. Jose ◽  
Santiago Cuevas
Keyword(s):  
Oxidative Stress ◽  
T Cell ◽  
Cell Infiltration ◽  
Mitochondrial Oxidative Stress ◽  
T Cell Infiltration
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