SMAD4 Expression in Monocytes as a Potential Biomarker for Atherosclerosis Risk in Patients with Obstructive Sleep Apnea
Abstract
:1. Introduction
2. Results
2.1. Subject Characteristics
2.2. Patients with Atherosclerosis Exhibited Elevated sSMAD4 Levels
2.3. sSMAD4 Levels Are Elevated in Patients with OSA and eSA and Related to OSA Severity
2.4. Intracellular SMAD4 Levels Where Higher in Monocytes from Patients with OSA
2.5. SMAD4 Expression and Release Is Related to Intermittent Hypoxia
2.6. NLRP3 Inflammasome Could Mediate SMAD4 Release to the Plasma
3. Discussion
4. Materials and Methods
4.1. Study Subjects
4.2. Plasma Protein Determination
4.3. Human Cell Isolation
4.4. Flow Cytometry
4.5. mRNA Isolation and Quantification by qPCR
4.6. Intermittent Hypoxia In Vitro Model
4.7. NLRP3 Inhibition Ex Vivo Model
4.8. 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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Subjects with Atherosclerotic Plaques | Subjects without Atherosclerotic Plaques | |||||||
---|---|---|---|---|---|---|---|---|
Overall | Overall | p-Value | Healthy Subjects | OSA Patients | p-Value | |||
Non-Early Subclinical Atherosclerosis (HS-non-eSA) | Early Subclinical Atherosclerosis (HS-eSA) | Non-Early Subclinical Atherosclerosis (OSA-non-eSA) | Early Subclinical Atherosclerosis (OSA-eSA) | |||||
n | 44 | 168 | - | 62 | 7 | 69 | 30 | - |
Male sex, n (%) | 36 (81) | 114 (67) | 0.070 | 35 (56) | 5 (71) | 52 (75) | 22 (73) | 0.08 |
Age, years | 51 (45–57) | 43 (36–52) | 0.001 | 36 (33–43) | 45 (41–51) * | 43 (38–58) # | 53 (47–59) * | <0.0001 |
Body mass index, kg/m2 | 30.2 (27.3–33.3) | 29.5 (26.5–33.9) | 0.890 | 27.4 (24.5–30) | 30.2 (27.1–32.8) | 30.1 (27.2–34.6) # | 32.3 (29.8–37.1) | <0.0001 |
Body fat, % | 32.3 (28.6–37.1) | 32.8 (27.2–40) | 0.458 | 32 (23.3–40.7) | 34.6 (27.7–42.1) | 33.9 (27.8–39.5) # | 32.6 (28.6–39.6) # | 0.537 |
Current smoker, n (%) | 11 (25) | 37 (22) | 0.675 | 12 (19) | 0 (0) | 16 (23) | 9 (30) | 0.334 |
Former smoker, n (%) | 18 (41) | 45 (27) | 0.070 | 18 (29) | 3 (43) | 16 (23) | 8 (27) | 0.674 |
Pack-years | 15 (0–30) | 0 (0–14) | 0.002 | 0 (0–14) | 0 (0–19) | 0 (0–11) | 7 (0–27) | 0.174 |
Epworth Sleepiness Scale | 8 (5–12) | 10 (6–13) | 0.108 | 9 (6–13) | 10 (8–14) | 14 (2.5–33) | 20 (6.7–46.2) | 0.329 |
AHI, events/h | 32.5 (14.8–61.5) | 18 (5–45.6) | 0.012 | 4 (1.2–7.2) | 4 (2–8) | 35.0 (21.5–62.5) # | 42 (27.7–59.2) # | <0.0001 |
ODI, events/h | 35.5 (15.7–51.2) | 21 (2–43) | 0.036 | 0 (0–2) | 2.5 (1.5–3.5) | 29 (17–49) # | 40 (26–60) # | <0.0001 |
CT90, % | 14 (2–35.3) | 5 (0–20.5) | 0.018 | 0 (0–2) | 0 (0–1) | 10 (1.5–25) # | 20 (6–43.5) # | <0.0001 |
Mean nocturnal SaO2, % | 92.5 (91–94) | 94 (92–95) | 0.100 | 95 (94–96) | 94 (94–95) | 93 (91–94) # | 92 (90–93) | <0.0001 |
Low nocturnal SaO2, % | 78 (71–85) | 83 (75–88) | 0.018 | 88 (84–92) | 89 (83–92) | 79 (71–84) # | 77 (70–82) # | <0.0001 |
Systolic BP, mm Hg | 133 (128–144) | 126 (116–134) | 0.0002 | 120 (111–131) | 124 (115–130) | 127 (120–134) | 132 (123–145) | 0.0002 |
Diastolic BP, mm Hg | 85 (76–94) | 80 (71–87) | 0.029 | 74 (68–82) | 81 (73–91) | 85 (76–91) # | 83 (75–95) | 0.0001 |
IMT, mm | 0.65 (0.58–0.76) | 0.59 (0.53–0.72) | 0.042 | 0.53 (0.50–0.57) | 0.86 (0.82–0.90) * | 0.59 (0.54–0.63) # | 0.86 (0.82–0.90) * | <0.0001 |
Non-Apneic Healthy Subjects (n = 20) | Severe OSA Patients (n = 50) | p-Value | |
---|---|---|---|
Male sex, n (%) | 12 (60) | 44 (73) | 0.260 |
Age, years | 51 (47–58) | 58 (51–64) | 0.176 |
Body mass index, kg/m2 | 28.3 (25.7–34.5) | 31.2 (28.4–33.8) | 0.105 |
Current smoker n (%) | 4 (20) | 9 (15) | 0.433 |
Former smoker n (%) | 2 (10) | 11 (18.3) | 0.363 |
Epworth Sleepiness Scale | 2 (0–4) | 8 (5–13) | <0.001 |
AHI, events/h | 3.2 (1.1–5.8) | 47.5 (36.4–67.25) | <0.001 |
ODI, events/h | 3 (0–5.2) | 46 (33.9–62.5) | <0.001 |
Mean nocturnal SaO2, % | 94 (93–96) | 90 (88–92) | <0.001 |
Low nocturnal SaO2, % | 89 (82–93) | 75 (65.5–80) | <0.001 |
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Díaz-García, E.; García-Sánchez, A.; Sánz-Rubio, D.; Alfaro, E.; López-Fernández, C.; Casitas, R.; Mañas Baena, E.; Cano-Pumarega, I.; Cubero, P.; Marin-Oto, M.; et al. SMAD4 Expression in Monocytes as a Potential Biomarker for Atherosclerosis Risk in Patients with Obstructive Sleep Apnea. Int. J. Mol. Sci. 2023, 24, 7900. https://doi.org/10.3390/ijms24097900
Díaz-García E, García-Sánchez A, Sánz-Rubio D, Alfaro E, López-Fernández C, Casitas R, Mañas Baena E, Cano-Pumarega I, Cubero P, Marin-Oto M, et al. SMAD4 Expression in Monocytes as a Potential Biomarker for Atherosclerosis Risk in Patients with Obstructive Sleep Apnea. International Journal of Molecular Sciences. 2023; 24(9):7900. https://doi.org/10.3390/ijms24097900
Chicago/Turabian StyleDíaz-García, Elena, Aldara García-Sánchez, David Sánz-Rubio, Enrique Alfaro, Cristina López-Fernández, Raquel Casitas, Eva Mañas Baena, Irene Cano-Pumarega, Pablo Cubero, Marta Marin-Oto, and et al. 2023. "SMAD4 Expression in Monocytes as a Potential Biomarker for Atherosclerosis Risk in Patients with Obstructive Sleep Apnea" International Journal of Molecular Sciences 24, no. 9: 7900. https://doi.org/10.3390/ijms24097900