Atrial Fibrillation in Heart Failure Is Associated with High Levels of Circulating microRNA-199a-5p and 22–5p and a Defective Regulation of Intracellular Calcium and Cell-to-Cell Communication
Abstract
:1. Introduction
2. Results
2.1. HFrEF Patients with AF Have Higher Plasmatic Levels of miRNA-199a-5p and miRNA-22-5p
2.2. MiR-199a-5p and 22–5p Expression Levels Are Higher in Atrial Samples of AF Patients
2.3. Overexpression of miR-199a-5p and miR-22-5p Is Associated with Reduced Expression of Proteins Involved in Ca2+ Homeostasis and Cell-to-Cell Communication
2.4. Overexpression of miR-199a-5p and miR-22-5p Is Associated with Reduced Intracellular Ca2+ Levels and a Decrease in Barium Currents (IBa)
2.5. Cells Transfected with miR-199a-5p and miR-22-5p Have Higher Ca2+ Levels in the Sarcoplasmic Reticulum and a Slower Caffeine-Induced Ca2+ Decay
2.6. Overexpression of miR-199a-5p and miR-22-5p Is Associated with a Reduction in Cx40 and Impaired Cell-to-Cell Communication
3. Discussion
4. Materials and Methods
4.1. Human Plasma Study
4.1.1. Study Population
4.1.2. Experimental Design
4.1.3. MicroRNA Extraction and Profiling
4.2. Human Atrial Samples
4.2.1. Cardiac Tissue Collection
4.2.2. MicroRNA Profiling
4.3. Molecular Studies
4.3.1. Cell Cultures and Transfection
4.3.2. qPCR and Western Blot Analyses
4.3.3. Recordings of Intracellular Ca2+ and Patch Clamp Studies
4.3.4. Gap-Junction Monitoring
4.4. Statistical Analyses
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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permAF (n = 40) | SR (n = 40) | p-Value | |
---|---|---|---|
Patient Characteristics | |||
Sex, men (%) | 31 (77.5) | 31 (77.5) | NS |
Age, y (SD) | 73.2 (10.1) | 73.5 (10.3) | NS |
BMI, kg/m2 (SD) | 30.5 (6.8) | 27.5 (3.7) | 0.02 |
Medical history | |||
Tobacco history (%) | 22 (55) | 22 (55) | NS |
Hypertension (%) | 30 (75) | 31 (77.5) | NS |
Diabetes (%) | 14 (35) | 18 (45) | NS |
Hypercholesterolemia (%) | 20 (50) | 21 (52.5) | NS |
COPD (%) | 6 (15) | 11 (27.5) | NS |
CKD (%) | 11 (27.5) | 8 (20.0) | NS |
Previous stroke (%) | 8 (20.0) | 4 (10.0) | NS |
HF parameters | |||
Ischemic etiology (%) | 16 (40) | 24 (60) | NS |
Heart rate, bpm (SD) | 76.5 (16.6) | 70.0 (14.6) | NS |
NYHA class (%): | NS | ||
I-II | 16 (51.6) | 24 (75) | |
III-IV | 15 (48.4) | 8 (25) | |
LVEF, % (SD) | 32.5 (6.7) | 32.8 (6.5) | NS |
Log Pro-BNP, mean (SD) | 3.4 (0.4) | 3.3 (0.6) | NS |
HF treatment | |||
ACEI/ARB (%) | 34 (85.0) | 33 (82.5) | NS |
Betablockers (%) | 37 (92.5) | 37 (92.5) | NS |
Diuretics (%) | 40 (100) | 37 (92.5) | NS |
Heart rhythm | <0.001 | ||
Permanent SR | 0 | 40 | |
History of parox/pers AF * | 0 | 0 | |
Permanent AF # | 40 | 0 |
2−△△Ct (permAF vs. SR) | p-Value | |
---|---|---|
miR-106a-5p | 1.292 | 0.378 |
miR-106b-5p | 1.311 | 0.275 |
miR-125a-5p | 1.395 | 0.110 |
miR-126-5p | 1.244 | 0.258 |
miR-133a-3p | 1.554 | 0.073 |
miR-16-5p | 0.955 | 0.783 |
miR-17-5p | 1.230 | 0.283 |
miR-199a-5p | 1.921 | 0.028 * |
miR-19a-3p | 1.526 | 0.117 |
miR-20a-5p | 1.158 | 0.452 |
miR-22-5p | 1.549 | 0.033 * |
miR-23a-3p | 1.278 | 0.219 |
miR-26a-5p | 1.322 | 0.187 |
miR-27b-3p | 1.402 | 0.153 |
miR-301a-3p | 1.115 | 0.765 |
miR-324-5p | 1.531 | 0.088 |
miR-374a-5p | 1.239 | 0.433 |
miR-425-3p | 1.450 | 0.119 |
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Garcia-Elias, A.; Tajes, M.; Yañez-Bisbe, L.; Enjuanes, C.; Comín-Colet, J.; Serra, S.A.; Fernández-Fernández, J.M.; Aguilar-Agon, K.W.; Reilly, S.; Martí-Almor, J.; et al. Atrial Fibrillation in Heart Failure Is Associated with High Levels of Circulating microRNA-199a-5p and 22–5p and a Defective Regulation of Intracellular Calcium and Cell-to-Cell Communication. Int. J. Mol. Sci. 2021, 22, 10377. https://doi.org/10.3390/ijms221910377
Garcia-Elias A, Tajes M, Yañez-Bisbe L, Enjuanes C, Comín-Colet J, Serra SA, Fernández-Fernández JM, Aguilar-Agon KW, Reilly S, Martí-Almor J, et al. Atrial Fibrillation in Heart Failure Is Associated with High Levels of Circulating microRNA-199a-5p and 22–5p and a Defective Regulation of Intracellular Calcium and Cell-to-Cell Communication. International Journal of Molecular Sciences. 2021; 22(19):10377. https://doi.org/10.3390/ijms221910377
Chicago/Turabian StyleGarcia-Elias, Anna, Marta Tajes, Laia Yañez-Bisbe, Cristina Enjuanes, Josep Comín-Colet, Selma A. Serra, José M. Fernández-Fernández, Kathryn W. Aguilar-Agon, Svetlana Reilly, Julio Martí-Almor, and et al. 2021. "Atrial Fibrillation in Heart Failure Is Associated with High Levels of Circulating microRNA-199a-5p and 22–5p and a Defective Regulation of Intracellular Calcium and Cell-to-Cell Communication" International Journal of Molecular Sciences 22, no. 19: 10377. https://doi.org/10.3390/ijms221910377