677 Inhibition of p38 MAP kinase improves endothelial dysfunction in chronic heart failure: role of vascular superoxide anion production

2003 ◽  
Vol 2 (1) ◽  
pp. 139
Author(s):  
J WIDDER ◽  
T BEHR ◽  
K HU ◽  
M BEROVA ◽  
C ANGERMANN ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Endothelial Dysfunction ◽  
Map Kinase ◽  
Superoxide Anion ◽  
P38 Map Kinase ◽  
Superoxide Anion Production ◽  
Anion Production

scholarly journals Role of TSPO/VDAC1 Upregulation and Matrix Metalloproteinase-2 Localization in the Dysfunctional Myocardium of Hyperglycaemic Rats

2020 ◽  
Vol 21 (20) ◽  
pp. 7432 ◽  
Author(s):  
Micaela Gliozzi ◽  
Federica Scarano ◽  
Vincenzo Musolino ◽  
Cristina Carresi ◽  
Miriam Scicchitano ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Nadph Oxidase ◽  
Diabetic Cardiomyopathy ◽  
Superoxide Anion ◽  
Matrix Metalloproteinase 2 ◽  
Superoxide Anion Production ◽  
Anion Production ◽  
Voltage Dependent ◽  
Selective Channel

Clinical management of diabetic cardiomyopathy represents an unmet need owing to insufficient knowledge about the molecular mechanisms underlying the dysfunctional heart. The aim of this work is to better clarify the role of matrix metalloproteinase 2 (MMP-2) isoforms and of translocator protein (TSPO)/voltage-dependent anion-selective channel 1 (VDAC1) modulation in the development of hyperglycaemia-induced myocardial injury. Hyperglycaemia was induced in Sprague-Dawley rats through a streptozocin injection (35 mg/Kg, i.p.). After 60 days, cardiac function was analysed by echocardiography. Nicotinamide Adenine Dinucleotide Phosphate NADPH oxidase and TSPO expression was assessed by immunohistochemistry. MMP-2 activity was detected by zymography. Superoxide anion production was estimated by MitoSOX™ staining. Voltage-dependent anion-selective channel 1 (VDAC-1), B-cell lymphoma 2 (Bcl-2), and cytochrome C expression was assessed by Western blot. Hyperglycaemic rats displayed cardiac dysfunction; this response was characterized by an overexpression of NADPH oxidase, accompanied by an increase of superoxide anion production. Under hyperglycaemia, increased expression of TSPO and VDAC1 was detected. MMP-2 downregulated activity occurred under hyperglycemia and this profile of activation was accompanied by the translocation of intracellular N-terminal truncated isoform of MMP-2 (NT-MMP-2) from mitochondria-associated membrane (MAM) into mitochondria. In the onset of diabetic cardiomyopathy, mitochondrial impairment in cardiomyocytes is characterized by the dysregulation of the different MMP-2 isoforms. This can imply the generation of a “frail” myocardial tissue unable to adapt itself to stress.

Endothelial Dysfunction Coincides With an Enhanced Nitric Oxide Synthase Expression and Superoxide Anion Production

Hypertension ◽  
1997 ◽  
Vol 30 (4) ◽  
pp. 934-941 ◽  
Author(s):  
Anne Bouloumié ◽  
Johann Bauersachs ◽  
Wolfgang Linz ◽  
Bernward A. Schölkens ◽  
Gabriele Wiemer ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Nitric Oxide Synthase ◽  
Superoxide Anion ◽  
Superoxide Anion Production ◽  
Anion Production ◽  
Oxide Synthase

Homocysteine stimulates NADPH oxidase-mediated superoxide production leading to endothelial dysfunction in rats

2007 ◽  
Vol 85 (12) ◽  
pp. 1236-1247 ◽  
Author(s):  
Vathsala E.R. Edirimanne ◽  
Connie W.H. Woo ◽  
Yaw L. Siow ◽  
Grant N. Pierce ◽  
Jiu Y. Xie ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Nadph Oxidase ◽  
Superoxide Anion ◽  
Vascular Wall ◽  
Oxidase Inhibitor ◽  
Vascular Cells ◽  
Superoxide Anion Production ◽  
Anion Production ◽  
Nadph Oxidase Activation ◽  
Endothelium Dependent Relaxation

Elevation of blood homocysteine (Hcy) levels (hyperhomocysteinemia) is a risk factor for cardiovascular disorders. We previously reported that oxidative stress contributed to Hcy-induced inflammatory response in vascular cells. In this study, we investigated whether NADPH oxidase was involved in Hcy-induced superoxide anion accumulation in the aorta, which leads to endothelial dysfunction during hyperhomocysteinemia. Hyperhomocysteinemia was induced in rats fed a high-methionine diet. NADPH oxidase activity and the levels of superoxide and peroxynitrite were markedly increased in aortas isolated from hyperhomocysteinemic rats. Expression of the NADPH oxidase subunit p22phox increased significantly in these aortas. Administration of an NADPH oxidase inhibitor (apocynin) not only attenuated aortic superoxide and peroxynitrite to control levels but also restored endothelium-dependent relaxation in the aortas of hyperhomocysteinemic rats. Transfection of human endothelial cells or vascular smooth muscle cells with p22phox siRNA to inhibit NADPH oxidase activation effectively abolished Hcy-induced superoxide anion production, thus indicating the direct involvement of NADPH oxidase in elevated superoxide generation in vascular cells. Taken together, these results suggest that Hcy-stimulated superoxide anion production in the vascular wall is mediated through the activation of NADPH oxidase, which leads to endothelial dysfunction during hyperhomocysteinemia.

Endothelial dysfunction in growth hormone transgenic mice

2006 ◽  
Vol 110 (2) ◽  
pp. 217-225 ◽  
Author(s):  
Irene J. Andersson ◽  
Maria E. Johansson ◽  
Anna Wickman ◽  
Mohammad Bohlooly-Y ◽  
Natalia Klintland ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Transgenic Mice ◽  
Endothelial Function ◽  
Vascular Function ◽  
Superoxide Anion ◽  
Carotid Arteries ◽  
Relaxation Response ◽  
Superoxide Anion Production ◽  
Anion Production

Acromegaly [overproduction of GH (growth hormone)] is associated with cardiovascular disease. Transgenic mice overexpressing bGH (bovine GH) develop hypertension and hypercholesterolaemia and could be a model for cardiovascular disease in acromegaly. The aims of the present study were to investigate the effects of excess GH on vascular function and to test whether oxidative stress affects endothelial function in bGH transgenic mice. We studied the ACh (acetylcholine)-induced relaxation response in aortic and carotid rings of young (9–11 weeks) and aged (22–24 weeks) female bGH transgenic mice and littermate control mice, without and with the addition of a free radical scavenger {MnTBAP [Mn(III)tetrakis(4-benzoic acid)porphyrin chloride]}. We also measured mRNA levels of eNOS (endothelial nitric oxide synthase) and EC-SOD (extracellular superoxide dismutase). Intracellular superoxide anion production in the vascular wall was estimated using a dihydroethidium probe. Carotid arteries from bGH transgenic mice had an impaired ACh-induced relaxation response (young, 46±7% compared with 69±8%; aged, 52±5% compared with 80±3%; P<0.05), whereas endothelial function in aorta was intact in young but impaired in aged bGH transgenic mice. Endothelial dysfunction was corrected by addition of MnTBAP in carotid arteries from young mice and in aortas from aged mice; however, MnTBAP did not correct endothelial dysfunction in carotid arteries from aged bGH transgenic mice. There was no difference in intracellular superoxide anion production between bGH transgenic mice and control mice, whereas mRNA expression of EC-SOD and eNOS was increased in aortas from young bGH transgenic mice compared with control mice (P<0.05). We interpret these data to suggest that bGH overexpression is associated with a time- and vessel-specific deterioration in endothelial function, initially caused by increased oxidative stress and later by other alterations in vascular function.

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