Natalya S Zinkevich1,2, Ibra S Fancher3, David D Gutterman1, Shane A Phillips4. 1. Cardiovascular Center, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA. 2. Department of Health and Medicine, Carroll University, Waukesha, WI, USA. 3. Department of Physical Therapy, Department of Medicine (Division of Pulmonary, Critical Care, Sleep and Allergy), University of Illinois at Chicago, Chicago, IL, USA. 4. Department of Physical Therapy, Department of Medicine (Division of Endocrinology, Diabetes and Metabolism), Integrative Physiology Laboratory, University of Illinois at Chicago, Chicago, IL, USA.
Abstract
OBJECTIVES: H2 O2 contributes to FID of human arterioles. This study is designed to examine the roles of mitochondria and NADPH oxidase in modulating the release of ROS and in mediating FID. We tested whether NADPH oxidase contributes to mitochondrial ROS generation in arterioles during CAD. METHODS: Visceral adipose arterioles obtained from patients with or without CAD were cannulated and pressurized for videomicroscopic measurement of arteriolar diameters. Dilator responses and ROS production during flow were determined in the presence and absence of the NADPH oxidase inhibitor gp91ds-tat and the mitochondrial electron transport inhibitor rotenone. RESULTS: Both dilation and H2 O2 generation during flow were reduced in the presence of rotenone (13.5±8% vs 97±% without rotenone) or gp91ds-tat in patients with CAD, while patients without CAD exhibited H2 O2 -independent dilations. Mitochondrial superoxide production during flow was attenuated by gp91ds-tat in arterioles from CAD patients. CONCLUSIONS: These findings indicate that ROS produced by NADPH oxidase are an upstream component of the mitochondria-dependent pathway contributing to flow-dependent H2 O2 generation and dilation in peripheral microvessels from patients with CAD. We conclude that in CAD, both mitochondria and NADPH oxidase contribute to FID through a redox mechanism in visceral arterioles.
OBJECTIVES:H2 O2 contributes to FID of human arterioles. This study is designed to examine the roles of mitochondria and NADPH oxidase in modulating the release of ROS and in mediating FID. We tested whether NADPH oxidase contributes to mitochondrial ROS generation in arterioles during CAD. METHODS: Visceral adipose arterioles obtained from patients with or without CAD were cannulated and pressurized for videomicroscopic measurement of arteriolar diameters. Dilator responses and ROS production during flow were determined in the presence and absence of the NADPH oxidase inhibitor gp91ds-tat and the mitochondrial electron transport inhibitor rotenone. RESULTS: Both dilation and H2 O2 generation during flow were reduced in the presence of rotenone (13.5±8% vs 97±% without rotenone) or gp91ds-tat in patients with CAD, while patients without CAD exhibited H2 O2 -independent dilations. Mitochondrial superoxide production during flow was attenuated by gp91ds-tat in arterioles from CAD patients. CONCLUSIONS: These findings indicate that ROS produced by NADPH oxidase are an upstream component of the mitochondria-dependent pathway contributing to flow-dependent H2 O2 generation and dilation in peripheral microvessels from patients with CAD. We conclude that in CAD, both mitochondria and NADPH oxidase contribute to FID through a redox mechanism in visceral arterioles.
Authors: D Sun; A Huang; C J Smith; C J Stackpole; J A Connetta; E G Shesely; A Koller; G Kaley Journal: Circ Res Date: 1999-08-06 Impact factor: 17.367
Authors: T Matoba; H Shimokawa; M Nakashima; Y Hirakawa; Y Mukai; K Hirano; H Kanaide; A Takeshita Journal: J Clin Invest Date: 2000-12 Impact factor: 14.808
Authors: Christophe A Wyss; Pascal Koepfli; Mehdi Namdar; Patrick T Siegrist; Thomas F Luscher; Paolo G Camici; Philipp A Kaufmann Journal: Eur J Nucl Med Mol Imaging Date: 2004-07-31 Impact factor: 9.236
Authors: Jing-Tan Bian; Mariann R Piano; Kumar U Kotlo; Abeer M Mahmoud; Shane A Phillips Journal: Alcohol Clin Exp Res Date: 2017-12-27 Impact factor: 3.455
Authors: Dawid S Chabowski; Andrew O Kadlec; Karima Ait-Aissa; Joseph C Hockenberry; Paul J Pearson; Andreas M Beyer; David D Gutterman Journal: Br J Pharmacol Date: 2018-10-11 Impact factor: 8.739
Authors: Sang Joon Ahn; Elizabeth Le Master; James C Lee; Shane A Phillips; Irena Levitan; Ibra S Fancher Journal: Am J Physiol Heart Circ Physiol Date: 2021-12-10 Impact factor: 4.733
Authors: Yangjing Xie; Yoshinori Nishijima; Natalya S Zinkevich; Ankush Korishettar; Juan Fang; Angela J Mathison; Michael T Zimmermann; David A Wilcox; David D Gutterman; Yuxian Shen; David X Zhang Journal: Basic Res Cardiol Date: 2022-04-25 Impact factor: 12.416
Authors: Danielle L Kirkman; Austin T Robinson; Matthew J Rossman; Douglas R Seals; David G Edwards Journal: Am J Physiol Heart Circ Physiol Date: 2021-04-09 Impact factor: 5.125
Authors: Xiaoling Li; Gregor Römer; Raphaela P Kerindongo; Jeroen Hermanides; Martin Albrecht; Markus W Hollmann; Coert J Zuurbier; Benedikt Preckel; Nina C Weber Journal: Int J Mol Sci Date: 2021-06-03 Impact factor: 5.923