The Roles of S100A4 and the EGF/EGFR Signaling Axis in Pulmonary Hypertension with Right Ventricular Hypertrophy
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Ethics Statement
2.2. Study Design and Groups
2.3. Serum Sample Collection
2.4. Analyte Quantifications
2.5. Tissue Sample Collection and Immunohistochemistry (IHC)
2.6. Statistical Methods
3. Results
3.1. CTEPH and iPAH Display Decreased Serum S100A4 Levels Compared to AVS and Healthy Individuals
3.2. Elevated EGF Concentration in CTEPH Compared to AVS and Controls
3.3. Downregulation of Systemic EGFR Levels in CTEPH, iPAH, and AVS Compared to Controls
3.4. Serum Analyte Concentrations Remain Unaltered by Surgical Interventions
3.5. S100A4 Expression in Lung Tissue Positively Correlates with Advanced Heath–Edwards Stages
4. Discussion
Limitations
5. Conclusions
6. Patents
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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CTEPH | Control | p-Value | |
---|---|---|---|
n | 37 | 39 | |
follow-up (n) | 23 | ||
age in years * | 57.54 (61.00) ± 13.37 [31–78] | 52.44 (53) ± 13.16 [31–80] | 0.111 |
F:M ratio [%] | 13:24 (35.1:64.9) | 15:19 (44.1:55.9) | 0.475 |
initial NYHA 1 | 2.89 (3) ± 0.68 [2–4] | ||
prePAPmean * [mmHg] 2 | 49.65 (50.5) ± 14.26 [27–90] | ||
postPAPmean * [mmHg] 2 | 27.33 (27) ± 6.08 [14–41] | <0.0001 § | |
prePVR * [mmHg × min/L] 2 | 8.48 (8.22) ± 2.89 [3.43–12.74] | ||
postPVR * [mmHg × min/L] 2 | 2.66 (2.37) ± 1.33 [0.84–4.66] | <0.0001 § | |
preCI * [L/min/m2] 2 | 2.33 (2.22) ± 0.5 [1.59–4.2] | ||
postCI * [L/min/m2] 2 | 3.08 (2.94) ± 0.94 [1.8–6.3] | 0.0007 § | |
S100A4 * [pg/mL] 3 | 1394.44 (1231.8) ± 960.41 [128.37–3564.6] | 2065.60 (1992.85) ± 648.39 [668.57–3739.46] | 0.002 |
EGF * [pg/mL] 3 | 926.61 (933.83) ± 576.61 [43.45–2149.12] | 520.01 (443.74) ± 464.24 [43.46–1658.42] | 0.003 |
EGFR * [ng/mL] 3 | 38.52 (39.84) ± 15.81 [5.3–81.77] | 47.05 (45.52) ± 11.64 [34.54–92.22] | 0.021 |
iPAH | Control | p-Value | |
---|---|---|---|
n | 19 | 24 | |
follow-up (n) | 7 | ||
age in years * | 37.84 (35) ± 8.34 [21–54] | 43.21 (38.5) ± 13.93 [26–76] | 0.126 |
F:M ratio [%] | 15:4 (78.9:21.1) | 17:7 (70.8:29.2) | 0.728 |
initial NYHA 1 | 3.85 (4) ± 0.36 [3–4] | ||
prePAPsys * [mmHg] 2 | 124.69 (120) ± 34.36 [65–180] | ||
prePAPmean * [mmHg] 2 | 66.25 (66) ± 24.55 [27–101] | ||
preCI * [L/min/m2] 2 | 2.27 (2.3) ± 0.2 [2–2.5] | ||
normal postPAPsys 3 | 7 of 11 patients (63.6%) § | ||
creatinine * [mg/dL] 4 | 1.02 (0.99) ± 0.32 [0.5–1.65] | ||
BUN * [mg/dL] 4 | 24.2 (17.45) ± 18.05 [8.5–73] | ||
protein serum * [g/L] 4 | 67.29 (69.35) ± 11.6 [39.7–83.3] | ||
cholinesterase * [k/U] 4 | 4.74 (4.71) ± 1.26 [1.8–6.25] | ||
S100A4 * [pg/mL] 5 | 1349.27 (1134.4) ± 894.64 [160.9–2905.4] | 2127.47 (2045.65) ± 706.82 [668.57–3630.87] | 0.007 |
EGF * [pg/mL] 5 | 766.01 (612.08) ± 669.87 [48.30–2313.62] | 511.86 (410.03) ± 460.25 [43.46–1658.42] | 0.311 |
EGFR * [ng/mL] 5 | 38.61 (36.12) ± 9.66 [24.24–63.33] | 49.08 (46.96) ±11.42 [36.45–92.22] | 0.001 |
AVS | Control | p-Value | |
---|---|---|---|
n | 15 | 21 | |
follow-up (n) | 15 | ||
age in years * | 65.23 (64.5) ± 10.31 [44–86] | 60.29 (61) ± 9.47 [38–80] | 0.146 |
F:M ratio [%] | 6:9 (40:60) | 8:13 (38.1:61.9) | 1.000 |
prePAPmean * [mmHg] 1 | 18.86 (19) ± 4.94 [9–28] | ||
Vmax * [m/s] 2 | 4.46 (4.3) ± 0.73 [3.8–6.2] | ||
ejection fraction * [%] 2 | 57.26 (57.00) ± 7.46 [45–73] | ||
creatinine * [mg/dL] 3 | 1.13 (0.96) ± 0.48 [0.67–2.1] | ||
cholesterol * [mmol/L] 3 | 4.36 (4.2) ± 0.99 [3–7.1] | ||
triglyceride * [mmol/L] 3 | 1.82 (1.5) ± 1.15 [0.69–4.9] | ||
S100A4 * [pg/mL] 4 | 2320.63 (2485.75) ± 727.22 [868.33–3268.11] | 2138.51 (2053) ± 745.94 [668.57–3739.46] | 0.465 |
EGF * [pg/mL] 4 | 331.32 (203.91) ± 408.01 [60.37–1577.63] | 506.45 (451.79) ± 473.49 [44.49–1658.42] | 0.400 |
EGFR * [ng/mL] 4 | 37.43 (33.67) ± 12.77 [22.27–73.45] | 44.76 (43.57) ± 9.18 [34.54–73.93] | 0.012 |
Cases per Group (%) | Numbers of Positively Stained Cases per Group (%) | |
---|---|---|
grade I lesions | 13 (44.8) | 4 (30.8) |
grade II lesions | 17 (58.6) | 17 (100) |
grade III lesions | 8 (27.6) | 8 (100) |
grade IV+ lesions | 8 (27.6) | 8 (100) |
peribronchial staining | 28 (96.6) | 27 (96.4) |
perivascular staining | 27 (93.1) | 0 (0) |
intima staining in larger vessels | 21 (72.4) | 17 (81) |
media staining in larger vessels | 21 (72.4) | 12 (57.1) |
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Laggner, M.; Hacker, P.; Oberndorfer, F.; Bauer, J.; Raunegger, T.; Gerges, C.; Szerafin, T.; Thanner, J.; Lang, I.; Skoro-Sajer, N.; et al. The Roles of S100A4 and the EGF/EGFR Signaling Axis in Pulmonary Hypertension with Right Ventricular Hypertrophy. Biology 2022, 11, 118. https://doi.org/10.3390/biology11010118
Laggner M, Hacker P, Oberndorfer F, Bauer J, Raunegger T, Gerges C, Szerafin T, Thanner J, Lang I, Skoro-Sajer N, et al. The Roles of S100A4 and the EGF/EGFR Signaling Axis in Pulmonary Hypertension with Right Ventricular Hypertrophy. Biology. 2022; 11(1):118. https://doi.org/10.3390/biology11010118
Chicago/Turabian StyleLaggner, Maria, Philipp Hacker, Felicitas Oberndorfer, Jonas Bauer, Thomas Raunegger, Christian Gerges, Tamás Szerafin, Jürgen Thanner, Irene Lang, Nika Skoro-Sajer, and et al. 2022. "The Roles of S100A4 and the EGF/EGFR Signaling Axis in Pulmonary Hypertension with Right Ventricular Hypertrophy" Biology 11, no. 1: 118. https://doi.org/10.3390/biology11010118
APA StyleLaggner, M., Hacker, P., Oberndorfer, F., Bauer, J., Raunegger, T., Gerges, C., Szerafin, T., Thanner, J., Lang, I., Skoro-Sajer, N., Ankersmit, H. J., & Moser, B. (2022). The Roles of S100A4 and the EGF/EGFR Signaling Axis in Pulmonary Hypertension with Right Ventricular Hypertrophy. Biology, 11(1), 118. https://doi.org/10.3390/biology11010118