The Nitric Oxide System in Peripheral Artery Disease: Connection with Oxidative Stress and Biopterins
Peripheral artery disease (PAD) pathophysiology extends beyond hemodynamics to include other operating mechanisms, including endothelial dysfunction. Oxidative stress may be linked to endothelial dysfunction by reducing nitric oxide (NO) bioavailability. We aimed to investigate whether the NO system...
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| Materiálatiipa: | Artihkal |
| Giella: | English |
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MDPI AG
2020-07-01
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| Ráidu: | Antioxidants |
| Fáttát: | |
| Liŋkkat: | https://www.mdpi.com/2076-3921/9/7/590 |
| _version_ | 1827713618899107840 |
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| author | Ahmed Ismaeel Evlampia Papoutsi Dimitrios Miserlis Ramon Lavado Gleb Haynatzki George P. Casale William T. Bohannon Robert S. Smith Jack Leigh Eidson Robert Brumberg Aaron Hayson Jeffrey S. Kirk Carlos Castro Ian Sawicki Charalambos Konstantinou Luke P. Brewster Iraklis I. Pipinos Panagiotis Koutakis |
| author_facet | Ahmed Ismaeel Evlampia Papoutsi Dimitrios Miserlis Ramon Lavado Gleb Haynatzki George P. Casale William T. Bohannon Robert S. Smith Jack Leigh Eidson Robert Brumberg Aaron Hayson Jeffrey S. Kirk Carlos Castro Ian Sawicki Charalambos Konstantinou Luke P. Brewster Iraklis I. Pipinos Panagiotis Koutakis |
| author_sort | Ahmed Ismaeel |
| collection | DOAJ |
| description | Peripheral artery disease (PAD) pathophysiology extends beyond hemodynamics to include other operating mechanisms, including endothelial dysfunction. Oxidative stress may be linked to endothelial dysfunction by reducing nitric oxide (NO) bioavailability. We aimed to investigate whether the NO system and its regulators are altered in the setting of PAD and to assess the relationship between NO bioavailability and oxidative stress. Sera from 35 patients with intermittent claudication (IC), 26 patients with critical limb ischemia (CLI), and 35 non-PAD controls were analyzed to determine levels of tetrahydrobiopterin (BH4), dihydrobiopterin (BH2), nitrate/nitrite (nitric oxides, or NOx), arginine, citrulline, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and the oxidative stress markers 8-Oxo-2′-deoxyguanosine (8-OHdG), 4-hydroxynonenal (4-HNE), advanced glycation end products (AGEs), and protein carbonyls. NOx was significantly lower in IC and CLI patients compared to controls in association with elevated oxidative stress, with the greatest NOx reductions observed in CLI. Compared with controls, IC and CLI patients had reduced BH4, elevated BH2, and a reduced BH4/BH2 ratio. SDMA, the arginine/SDMA ratio, and the arginine/ADMA ratio were significantly higher in CLI patients. The NO system and its regulators are significantly compromised in PAD. This dysregulation appears to be driven by increased oxidative stress and worsens as the disease progresses from claudication to CLI. |
| first_indexed | 2024-03-10T18:39:27Z |
| format | Article |
| id | doaj.art-610c7cbb1b1141d3b5cb076be7c8210c |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T18:39:27Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-610c7cbb1b1141d3b5cb076be7c8210c2023-11-20T05:58:06ZengMDPI AGAntioxidants2076-39212020-07-019759010.3390/antiox9070590The Nitric Oxide System in Peripheral Artery Disease: Connection with Oxidative Stress and BiopterinsAhmed Ismaeel0Evlampia Papoutsi1Dimitrios Miserlis2Ramon Lavado3Gleb Haynatzki4George P. Casale5William T. Bohannon6Robert S. Smith7Jack Leigh Eidson8Robert Brumberg9Aaron Hayson10Jeffrey S. Kirk11Carlos Castro12Ian Sawicki13Charalambos Konstantinou14Luke P. Brewster15Iraklis I. Pipinos16Panagiotis Koutakis17Department of Nutrition, Food and Exercise Sciences, Florida State University, Tallahassee, FL 32304, USADepartment of Nutrition, Food and Exercise Sciences, Florida State University, Tallahassee, FL 32304, USADepartment of Surgery, University of Texas Health Science Center San Antonio, San Antonio, TX 78229, USADepartment of Environmental Science, Baylor University, Waco, TX 76798, USADepartment of Biostatistics, University of Nebraska Medical Center, Omaha, NE 68198, USADepartment of Surgery, University of Nebraska Medical Center, Omaha, NE 68198, USADepartment of Surgery, Baylor Scott & White Medical Center, Temple, TX 76508, USADepartment of Surgery, Baylor Scott & White Medical Center, Temple, TX 76508, USADepartment of Surgery, Baylor Scott & White Medical Center, Temple, TX 76508, USAVascular Surgery Associates, Tallahassee, FL 32308, USAVascular Surgery Associates, Tallahassee, FL 32308, USADepartment of Vascular Surgery, Capital Regional Medical Center, Tallahassee, FL 32308, USADepartment of Vascular Surgery, Capital Regional Medical Center, Tallahassee, FL 32308, USADepartment of Surgery, Baylor Scott & White Medical Center, Temple, TX 76508, USADepartment of Electrical & Computer Engineering, Florida State University, Tallahassee, FL 32310, USADepartment of Surgery, Emory University School of Medicine, Atlanta, GA 30322, USADepartment of Surgery, University of Nebraska Medical Center, Omaha, NE 68198, USADepartment of Nutrition, Food and Exercise Sciences, Florida State University, Tallahassee, FL 32304, USAPeripheral artery disease (PAD) pathophysiology extends beyond hemodynamics to include other operating mechanisms, including endothelial dysfunction. Oxidative stress may be linked to endothelial dysfunction by reducing nitric oxide (NO) bioavailability. We aimed to investigate whether the NO system and its regulators are altered in the setting of PAD and to assess the relationship between NO bioavailability and oxidative stress. Sera from 35 patients with intermittent claudication (IC), 26 patients with critical limb ischemia (CLI), and 35 non-PAD controls were analyzed to determine levels of tetrahydrobiopterin (BH4), dihydrobiopterin (BH2), nitrate/nitrite (nitric oxides, or NOx), arginine, citrulline, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and the oxidative stress markers 8-Oxo-2′-deoxyguanosine (8-OHdG), 4-hydroxynonenal (4-HNE), advanced glycation end products (AGEs), and protein carbonyls. NOx was significantly lower in IC and CLI patients compared to controls in association with elevated oxidative stress, with the greatest NOx reductions observed in CLI. Compared with controls, IC and CLI patients had reduced BH4, elevated BH2, and a reduced BH4/BH2 ratio. SDMA, the arginine/SDMA ratio, and the arginine/ADMA ratio were significantly higher in CLI patients. The NO system and its regulators are significantly compromised in PAD. This dysregulation appears to be driven by increased oxidative stress and worsens as the disease progresses from claudication to CLI.https://www.mdpi.com/2076-3921/9/7/590tetrahydrobiopterindihydrobiopterinendothelial dysfunction |
| spellingShingle | Ahmed Ismaeel Evlampia Papoutsi Dimitrios Miserlis Ramon Lavado Gleb Haynatzki George P. Casale William T. Bohannon Robert S. Smith Jack Leigh Eidson Robert Brumberg Aaron Hayson Jeffrey S. Kirk Carlos Castro Ian Sawicki Charalambos Konstantinou Luke P. Brewster Iraklis I. Pipinos Panagiotis Koutakis The Nitric Oxide System in Peripheral Artery Disease: Connection with Oxidative Stress and Biopterins Antioxidants tetrahydrobiopterin dihydrobiopterin endothelial dysfunction |
| title | The Nitric Oxide System in Peripheral Artery Disease: Connection with Oxidative Stress and Biopterins |
| title_full | The Nitric Oxide System in Peripheral Artery Disease: Connection with Oxidative Stress and Biopterins |
| title_fullStr | The Nitric Oxide System in Peripheral Artery Disease: Connection with Oxidative Stress and Biopterins |
| title_full_unstemmed | The Nitric Oxide System in Peripheral Artery Disease: Connection with Oxidative Stress and Biopterins |
| title_short | The Nitric Oxide System in Peripheral Artery Disease: Connection with Oxidative Stress and Biopterins |
| title_sort | nitric oxide system in peripheral artery disease connection with oxidative stress and biopterins |
| topic | tetrahydrobiopterin dihydrobiopterin endothelial dysfunction |
| url | https://www.mdpi.com/2076-3921/9/7/590 |
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