Activation of the Interleukin-33/ST2 Pathway Exerts Deleterious Effects in Myxomatous Mitral Valve Disease
Abstract
:1. Introduction
2. Results
2.1. Clinicopathological Features of the Patients with MVD
2.2. Distribution of the IL-33 and ST2 within the Mitral Valve
2.3. Correlation of IL-33 in Myxomatous MVs with Inflammatory Mediators, Extracellular Matrix Components, and Matrix Metalloproteinases
2.4. IL-33 Induces Activation of Human Mitral VICs, Inflammation, Proteoglycans Synthesis and Extracellular Matrix Remodeling
2.5. IL-33 Induces EndMT in Valve Endothelial Cells and Extracellular Matrix Changes
3. Discussion
4. Materials and Methods
4.1. Patient Population
4.2. Immunohistological Evaluation
4.3. ELISA
4.4. Cell Isolation and Culture
4.5. Single Culture Cell Assays
4.6. Real-Time Reverse Transcription PCR
4.7. Western Blot Analysis
4.8. Statistical Analysis
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Clinicopathological Features | n |
---|---|
Total number of patients | 103 |
Age (years ± SD) | 68 ± 10 |
Male (N, % of total) | 68 (65) |
Hypertension (N, % of total) | 59 (56) |
Hypercholesterolemia (N, % of total) | 48 (46) |
Diabetes mellitus (N, % of total) | 9 (9) |
Coronary artery disease (N, % of total) | 22 (21) |
Atrial fibrillation (N, % of total) | 52 (50) |
Heart failure | |
NYHA functional class at the time of surgery (N, % of total) | |
I | 9 (9) |
II | 51 (49) |
III | 42 (40) |
IV | 1 (1) |
Previous admission for heart failure (N, % of total) | 20 (19) |
BNP (pg/mL ± SD) | 266 ± 342 |
CRP (µg/mL ± SD) | 2.84 ± 1.67 |
Medications | |
ACE inhibitors (N, % of total) | 38 (37) |
ARB (N, % of total) | 21 (20) |
Spironolactone (N, % of total) | 6 (6) |
Eplerenone (N, % of total) | 3 (3) |
Diuretics (N, % of total) | 80 (78) |
Betablockers (N, % of total) | 52 (51) |
Digoxin (N, % of total) | 18 (17) |
Statins (N, % of total) | 44 (43) |
Echocardiographic parameters | |
LVEF (mean ± SD) | 60.6 ± 10.4 |
Systolic dysfunction (LVEF <60 %) (N, % of total) | 36 (35) |
Severe systolic dysfunction (LVEF <35 %) (N, % of total) | 2 (2) |
End diastolic diameter (mm ± SD) | 59 ± 7 |
Indexed end diastolic diameter (mm/m2 ± SD) | 33 ± 4 |
End systolic diameter (mm ± SD) | 40 ± 8 |
Indexed end systolic diameter (mm/m2 ± SD) | 23 ± 7 |
Systolic pulmonary artery pressure (mmHg ± SD) | 47 ± 12 |
MVP etiologic subgroups | |
Barlow disease (N, % of total) | 70 (68) |
Fibroelastic deficiency (N, % of total) | 30 (29) |
Syndromic MVP | 1 (1) |
Associated to hypertrophic cardiomyopathy | 2 (2) |
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Garcia-Pena, A.; Ibarrola, J.; Navarro, A.; Sadaba, A.; Tiraplegui, C.; Garaikoetxea, M.; Arrieta, V.; Matilla, L.; Fernández-Celis, A.; Sadaba, R.; et al. Activation of the Interleukin-33/ST2 Pathway Exerts Deleterious Effects in Myxomatous Mitral Valve Disease. Int. J. Mol. Sci. 2021, 22, 2310. https://doi.org/10.3390/ijms22052310
Garcia-Pena A, Ibarrola J, Navarro A, Sadaba A, Tiraplegui C, Garaikoetxea M, Arrieta V, Matilla L, Fernández-Celis A, Sadaba R, et al. Activation of the Interleukin-33/ST2 Pathway Exerts Deleterious Effects in Myxomatous Mitral Valve Disease. International Journal of Molecular Sciences. 2021; 22(5):2310. https://doi.org/10.3390/ijms22052310
Chicago/Turabian StyleGarcia-Pena, Amaia, Jaime Ibarrola, Adela Navarro, Alba Sadaba, Carolina Tiraplegui, Mattie Garaikoetxea, Vanessa Arrieta, Lara Matilla, Amaya Fernández-Celis, Rafael Sadaba, and et al. 2021. "Activation of the Interleukin-33/ST2 Pathway Exerts Deleterious Effects in Myxomatous Mitral Valve Disease" International Journal of Molecular Sciences 22, no. 5: 2310. https://doi.org/10.3390/ijms22052310