Does Cell-Type-Specific Silencing of Monoamine Oxidase B Interfere with the Development of Right Ventricle (RV) Hypertrophy or Right Ventricle Failure in Pulmonary Hypertension?
Abstract
:1. Introduction
2. Results
2.1. Effect of cmMAO-B Knockout on Reactive Oxygen Species Formation
2.2. Effect of cmMAO-B Knockout on Right Ventricular Dimension and Function
2.3. Effect of cmMAO-B Knockout on Protein Kinase Activity during PAB
2.4. Effect of cmMAO-B Knockout on Cardiomyocyte Function
3. Discussion
3.1. Main Findings
3.2. MAO and ROS Formation
3.3. MAO Substrates
3.4. MAO and Pulmonary Hypertension
3.5. MAO and RV Geometry
3.6. MAO and Cardiomyocyte Function
4. Materials and Methods
4.1. Animals and Ethical Concerns
4.2. Pulmonary Artery Banding (PAB) In Vivo
4.3. Echocardiography
4.4. Invasive Hemodynamic Measurement
4.5. Isolation and Culture of Adult Mouse Ventricular Cardiomyocytes
4.6. Determination of Cell Contraction
4.7. Metabolome Analysis: Sample Extraction
4.8. LC-MS/MS Analysis
4.9. Detection of Intracellular ROS
4.10. Peptide-Based Kinase Activity Assay
4.11. Jess Simple Western System (ProteinSimple, San Jose, CA, USA)
4.12. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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RV | Ldiast (µm) | Con Vel (µm/s) | Rel Vel (µm/s) | dL/L (%) | |
---|---|---|---|---|---|
MAO-Bfl/fl | SHAM | 109.93 ± 9.79 | 202.63 ± 51.36 | 166.05 ± 45.05 | 8.53 ± 1.82 |
PAB | 111.32 ± 7.23 | 182.99 ± 46.88 | 151.03 ± 45.33 | 7.65 ± 7.65 | |
cmMAO-B KO | SHAM | 112.08 ± 11.66 | 215.58 ± 72.75 | 180.14 ± 59.07 | 9.10 ± 2.44 |
PAB | 108.36 ± 11.00 | 183.64 ± 48.88 | 152.43 ± 45.10 | 8.30 ± 2.08 |
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Brosinsky, P.; Heger, J.; Sydykov, A.; Weiss, A.; Klatt, S.; Czech, L.; Kraut, S.; Schermuly, R.T.; Schlüter, K.-D.; Schulz, R. Does Cell-Type-Specific Silencing of Monoamine Oxidase B Interfere with the Development of Right Ventricle (RV) Hypertrophy or Right Ventricle Failure in Pulmonary Hypertension? Int. J. Mol. Sci. 2024, 25, 6212. https://doi.org/10.3390/ijms25116212
Brosinsky P, Heger J, Sydykov A, Weiss A, Klatt S, Czech L, Kraut S, Schermuly RT, Schlüter K-D, Schulz R. Does Cell-Type-Specific Silencing of Monoamine Oxidase B Interfere with the Development of Right Ventricle (RV) Hypertrophy or Right Ventricle Failure in Pulmonary Hypertension? International Journal of Molecular Sciences. 2024; 25(11):6212. https://doi.org/10.3390/ijms25116212
Chicago/Turabian StyleBrosinsky, Paulin, Jacqueline Heger, Akylbek Sydykov, Astrid Weiss, Stephan Klatt, Laureen Czech, Simone Kraut, Ralph Theo Schermuly, Klaus-Dieter Schlüter, and Rainer Schulz. 2024. "Does Cell-Type-Specific Silencing of Monoamine Oxidase B Interfere with the Development of Right Ventricle (RV) Hypertrophy or Right Ventricle Failure in Pulmonary Hypertension?" International Journal of Molecular Sciences 25, no. 11: 6212. https://doi.org/10.3390/ijms25116212