Contribution of Mitochondrial Reactive Oxygen Species to Chronic Hypoxia-Induced Pulmonary Hypertension
Abstract
:1. Introduction
2. Methods
2.1. Animal Model
2.2. Contribution of mtROS to Chronic Hypoxia-Induced Pulmonary Hypertension
2.2.1. Experimental Groups
2.2.2. Echocardiography
2.2.3. Right Ventricular and Systemic Arterial Blood Pressure Measurement
2.2.4. Hematocrit
2.2.5. Fulton’s Index
2.2.6. Lung Fixation and Assessment of Pulmonary Arterial Remodeling
2.3. Pressure Myography
2.3.1. Basal Tone Measurement in Small Pulmonary Arteries
2.3.2. Vasoconstrictor Response to ET-1 in Small Endothelium-Disrupted PAs
2.4. MtROS Detection in Pulmonary Arterial Smooth Muscle Cells (PASMCs)
2.4.1. Establishment of Primary PASMC Cultures
2.4.2. Basal mtROS Measurement in PASMCs
2.4.3. ET-1 Induced mtROS Production in PASMCs by Live Cell Imaging
2.4.4. Confocal Microscopy and Image Quantification
2.5. MtROS in Acutely Isolated Endothelial Sheets
2.6. Statistical Analysis
3. Results
3.1. Involvement of MtROS in CH-Induced Pulmonary Hypertension
3.2. MtROS Mediate CH-Induced Increases in Pulmonary Arterial Tone
3.3. PASMC-Derived mtROS Contribute to Elevated PA Tone following CH
3.4. Endogenous ET-1 Contributes to Enhanced MtROS-Dependent Basal Tone following CH
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Measurement | Time of Exposure | Control | CH | ||
---|---|---|---|---|---|
Vehicle | MitoQ | Vehicle | MitoQ | ||
Cardiac output (mL/min/Kg) | Baseline | 277 ± 17 | 280 ± 27 | 275 ± 11 | 276 ± 24 |
2 weeks | 263 ± 11 | 266 ± 15 | 271 ± 15 | 266 ± 10 | |
4 weeks | 269 ± 16 | 270 ± 15 | 262 ± 20 | 260 ± 8 | |
HR (bpm) | Baseline | 391 ± 4 | 387 ± 5 | 391 ± 12 | 389 ± 5 |
2 weeks | 364 ± 5 | 370 ± 8 | 379 ± 10 | 369 ± 6 | |
4 weeks | 374 ± 11 | 371 ± 11 | 380 ± 7 | 384 ± 7 |
Measurement | Control | CH | ||
---|---|---|---|---|
Vehicle | MitoQ | Vehicle | MitoQ | |
MSAP (mmHg) | 113 ± 2 | 107 ± 2 | 117 ± 6 | 124 ± 2 * |
HR (bpm) | 362 ± 6 | 348 ± 14 | 350 ± 9 | 360 ± 8 |
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Yan, S.; Sheak, J.R.; Walker, B.R.; Jernigan, N.L.; Resta, T.C. Contribution of Mitochondrial Reactive Oxygen Species to Chronic Hypoxia-Induced Pulmonary Hypertension. Antioxidants 2023, 12, 2060. https://doi.org/10.3390/antiox12122060
Yan S, Sheak JR, Walker BR, Jernigan NL, Resta TC. Contribution of Mitochondrial Reactive Oxygen Species to Chronic Hypoxia-Induced Pulmonary Hypertension. Antioxidants. 2023; 12(12):2060. https://doi.org/10.3390/antiox12122060
Chicago/Turabian StyleYan, Simin, Joshua R. Sheak, Benjimen R. Walker, Nikki L. Jernigan, and Thomas C. Resta. 2023. "Contribution of Mitochondrial Reactive Oxygen Species to Chronic Hypoxia-Induced Pulmonary Hypertension" Antioxidants 12, no. 12: 2060. https://doi.org/10.3390/antiox12122060