Regulation of CD163 Receptor in Patients with Abdominal Aortic Aneurysm and Associations with Antioxidant Enzymes HO-1 and NQO1
Abstract
:1. Introduction
2. Methods
2.1. Acquisition of Aortic Tissue
2.2. Study Design and Study Participants
2.3. Outcome Variables, Confounders and Sample Size
2.4. Clinical Variables
2.5. Blood Sampling and Enzyme-Linked Immunosorbent Assay (ELISA) for Determination of sCD163
2.6. RNA Isolation, cDNA Synthesis, and Quantitative Real-Time Polymerase Chain Reaction (qPCR)
2.7. Statistical Analyses
3. Results
3.1. Patients’ Characteristics for Quantification of Aortic mRNA Expression
3.2. Aortic CD163 mRNA Expression and Linkage to the Antioxidant System
3.3. Patients’ Characteristics for Assessment of sCD163 and Bilirubin Concentrations
3.4. Diagnostic Value of sCD163 and Associations with Aortic Diameter, AAA Volume and Thickness of ILT
3.5. Serum Bilirubin of AAA Patients and Associations with Aortic Diameter, AAA Volume and Thickness of ILT
4. Discussion
5. Conclusions
6. Limitations
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Nonstandard Abbreviations and Acronyms
References
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Aortic mRNA Expression Study | |||||
---|---|---|---|---|---|
AOD | eAAA | rAAA | p-Value | χ2 | |
Baseline Demographics | |||||
n included | 6 | 35 | 11 | ||
Age, years, mean ± SD, n | 55.5 ± 7.47 6 | 64.80 ± 7.26 35 | 72.64 ± 6.30 11 | 0.0127 (AOD vs. eAAA) <0.0001 (AOD vs. rAAA) 0.0068 (eAAA vs. rAAA) | |
Sex, male:female, % male, n | 4:2, 67 6 | 32:3, 91 35 | 8:3, 73 11 | 0.14 | 3.93 |
Aortic diameter, mm, mean ± SD, n | 19.28 ± 4.16 6 | 62.20 ± 14.09 33 | 82.89 ± 17.97 10 | <0.0001 (AOD vs. eAAA) <0.0001 (AOD vs. rAAA) 0.0006 (eAAA vs. rAAA) | |
Thickness ILT, mm, median with range, n | n.d. | 16.70 (0.00–52.20) 31 | 30.60 (19.70–44.70) 9 | 0.001 | |
Hematology | |||||
Hemoglobin, mmol/L, mean ± SD, n | 7.52 ± 1.27 6 | 8.37 ± 1.43 35 | 7.35 ± 1.68 10 | 0.10 | |
Reference values 8.60–12.10 mmol/L | |||||
Leukocytes, GPt/L mean ± SD, n | 12.31 ± 4.10 6 | 8.00 ± 2.14 35 | 12.56 ± 4.91 10 | 0.0075 (AOD vs. eAAA) 0.0004 (eAAA vs. rAAA) | |
Reference values 3.8–9.8 GPt/L | |||||
Cardiovascular risk factors | |||||
LDL cholesterol, mmol/L, median with range, n | 1.47 (1.26–1.65) 4 | 2.52 (0.89–6.16) 21 | n.d. | 0.08 | |
Reference values < 1.40 mmol/L for people with very-high risk | |||||
HDL cholesterol, mmol/L, mean ± SD, n | 1.20 ± 0.28 4 | 1.18 ± 0.33 21 | n.d. | 0.94 | |
Reference values > 0.90 mmol/L for men and >1.10 mmol/L for women | |||||
Total cholesterol, mmol/L, mean ± SD, n | 2.97 ± 0.08 4 | 4.16 ± 1.34 21 | n.d. | 0.15 | |
Reference values < 4.00 mmol/L | |||||
Triglycerides, mmol/L, mean ± SD, n | 1.44 ± 0.39 5 | 1.91 ± 0.94 28 | n.d. | 0.28 | |
Reference values 0.35–1.70 mmol/L | |||||
Blood glucose, mmol/L, mean ± SD, n | 2.97 ± 0.08 4 | 5.55 ± 0.99 22 | n.d. | 0.0002 | |
Reference values only for fasting glucose | |||||
CRP, mg/L, median with range, n | 4.05 (1.20–18.00) 6 | 3.25 (0.50–21.00) 35 | 6.40 (0.50–65.00) 9 | 0.44 | |
Reference values < 5.0 mg/L | |||||
Smoking, yes:no, %, n | 5:1, 83 6 | 22:13, 63 35 | 4:7, 36 11 | 0.13 | 4.03 |
Hypertension, yes:no, %, n | 4:2, 67 6 | 29:6, 83 35 | 10:1, 91 11 | 0.45 | 1.60 |
CAD, yes:no, %, n | 3:3, 50 6 | 9:26, 26 35 | 4:7, 36 11 | 0.44 | 1.62 |
HF, yes:no, %, n | 3:3, 50 6 | 7:28, 20 35 | 2:9, 18 11 | 0.25 | 2.79 |
CAS, yes:no, %, n | 0:6, 0 6 | 1:34, 3 35 | 1:10, 9 11 | 0.56 | 1.15 |
PAD, yes:no, %, n | 6:0, 100 6 | 8:27, 23 35 | 2:9, 18 11 | 0.0005 | 15.35 |
T2D, yes:no—%, n | 1:5, 17 6 | 5:30, 12 35 | 2:9, 20 11 | 0.94 | 0.11 |
BMI, kg/m2, mean ± SD, n | 25.28 ± 6.40 6 | 27.02 ± 4.17 35 | 29.09 ± 5.76 10 | 0.29 | |
Medical therapies | |||||
Statins, yes:no, %, n | 5:1, 83 6 | 21:14, 60 35 | 6:4, 60 10 | 0.54 | 1.23 |
ACE inhibitors, yes:no, %, n | 0:6, 0 6 | 15:20, 43 35 | 4:6, 40 10 | 0.13 | 4.07 |
ARB, yes:no, %, n | 2:4, 33 6 | 12:23, 34 35 | 3:7, 30 10 | 0.97 | 0.06 |
CCB, yes:no, %, n | 0:6, 0 6 | 15:20, 43 35 | 4:6, 40 10 | 0.13 | 4.07 |
ASA, yes:no, %, n | 6:0, 100 6 | 19:16, 54 35 | 6:4, 60 10 | 0.11 | 4.49 |
β-blocker, yes:no, %, n | 2:4, 33 6 | 14:21, 40 35 | 4:6, 40 10 | 0.95 | 0.10 |
Anticoagulation, yes:no, %, n | 2:4, 33 6 | 6:29, 17 35 | 2:8, 20 10 | 0.65 | 0.85 |
Antiplatelet, yes:no, %, n | 1:5, 17 6 | 2:33, 6 35 | 2:8, 20 10 | 0.34 | 2.16 |
Diuretics, yes:no, %, n | 0:6, 0 6 | 11:24, 31 35 | 4:6, 40 10 | 0.21 | 3.11 |
T2D treatment, yes:no, %, n | 1:5, 17 6 | 4:31, 11 35 | 1:9, 10 10 | 0.92 | 0.17 |
Insulin, yes:no, %, n | 1:5, 17 6 | 2:33, 6 35 | 0:10, 0 10 | 0.39 | 1.89 |
Retrospective, Observational Study | ||||
---|---|---|---|---|
Varicosis | AAA | p-Value | χ2 | |
Baseline Demographics | ||||
n included | 54 | 86 | ||
Age, years, median with range, n | 63.50 (50.00–82.99) 54 | 73.50 (53.00–89.00) 86 | <0.0001 | |
Sex, male:female, % male, n | 27:27, 50 54 | 82:4, 95 86 | <0.0001 | 39.57 |
Hematology | ||||
Hemoglobin, mmol/L, mean ± SD, n | 8.88 ± 0.72 50 | 8.89 ± 1.04 86 | 0.97 | |
Reference values 8.60–12.10 mmol/L | ||||
Leukocytes, GPt/L, mean ± SD, n | 6.48 ± 1.50 50 | 7.54 ± 1.85 86 | 0.0007 | |
Reference values 3.8–9.8 GPt/L | ||||
Cardiovascular risk factors | ||||
LDL cholesterol, mmol/L, median with range, n | 3.33 (0.85–5.62) 50 | 2.21 (0.71–5.21) 82 | <0.0001 | |
Reference values < 1.40 mmol/L for people with very-high risk | ||||
HDL cholesterol, mmol/L, median with range, n | 1.64 (1.01–2.77) 49 | 1.26 (0.68–2.15) 83 | <0.0001 | |
Reference values > 0.90 mmol/L for men and >1.10 mmol/L for women | ||||
Total cholesterol, mmol/L, median with range, n | 5.40 (2.12–7.74) 49 | 3.97 (2.05–6.46) 82 | <0.0001 | |
Reference values < 4.00 mmol/L | ||||
Triglycerides, mmol/L, median with range, n | 1.28 (0.43–3.88) 50 | 1.48 (0.52–4.50) 83 | 0.24 | |
Reference values 0.35–1.70 mmol/L | ||||
Blood glucose, mmol/L, median with range, n | 5.21 (4.08–8.59) 49 | 5.51 (2.93–13.73) 85 | 0.06 | |
Reference value only for fasting glucose possible | ||||
CRP, mg/L, median with range, n | 1.30 (0.30–6.60) 49 | 2.40 (0.50–62.30 85 | 0.0003 | |
Reference values < 5.0 mg/L | ||||
Smoking, yes:no, %, n | 6:47, 11 53 | 45:41, 52 86 | <0.0001 | 23.74 |
Hypertension, yes:no, %, n | 27:26, 51 53 | 73:13, 85 86 | <0.0001 | 18.71 |
CAD, yes:no, %, n | 2:51, 4 53 | 32:54, 37 86 | <0.0001 | 19.84 |
HF, yes:no, %, n | 27:26, 51 53 | 73:13, 85 86 | <0.0001 | 18.71 |
CAS, yes:no, %, n | 0:53, 0 53 | 9:77, 10 86 | 0.02 | 5.93 |
PAD, yes:no, %, n | 0:53, 0 53 | 23:63, 27 86 | <0.0001 | 4.12 |
T2D, yes:no, %, n | 3:50, 6 53 | 23:63, 27 86 | 0.005 | 7.97 |
Renal failure, yes:no, %, n | 0:53, 0 53 | 11:75, 86 86 | 0.007 | 7.36 |
BMI, kg/m2, median with range, n | 27.10 (16.60–40.70) 54 | 27.40 (18.81–37.13) 85 | 0.55 | |
Medical therapies | ||||
Statins, yes:no, %, n | 11:42, 21 53 | 66:20, 77 86 | <0.0001 | 41.60 |
ACE inhibitors, yes:no, %, n | 10:43, 19 53 | 27:59, 31 86 | 0.11 | 2.64 |
ARB, yes:no, %, n | 14:39, 26 53 | 39:47, 74 86 | 0.03 | 4.98 |
CCB, yes:no, %, n | 11:42, 21 53 | 35:51, 41 86 | 0.02 | 5.89 |
ASA, yes:no, %, n | 3:50, 6 53 | 58:28, 67 86 | <0.0001 | 7.13 |
β-blocker, yes:no, %, n | 15:38, 28 53 | 43:43, 50 86 | 0.012 | 2.52 |
Anticoagulation, yes:no, %, n | 17:36, 59 53 | 12:74, 14 86 | 0.011 | 2.55 |
Antiplatelet, yes:no, %, n | 0:53, 0 53 | 9:77, 10 86 | 0.02 | 2.44 |
Diuretics, yes:no, %, n | 12:41, 23 53 | 36:50, 42 86 | 0.021 | 2.32 |
T2D treatment, yes:no, %, n | 2:51, 4 53 | 17:69, 20 86 | 0.008 | 7.11 |
Insulin, yes:no, %, n | 1:52, 2 53 | 5:81, 6 86 | 0.27 | 1.11 |
Univariable Analysis | Multivariate Analysis | |||||
---|---|---|---|---|---|---|
Variable | OR | CI | p-Value | OR | CI | p-Value |
Group (ref = varicose vein) | 1.191 | [1.036, 1.370] | 0.015 | 1.336 | [1.082, 1.649] | 0.008 |
Age | 1.010 | [1.003, 1.016] | 0.006 | 1.008 | [1.000, 1.015] | 0.054 |
Sex (ref = female) | 0.976 | [0.826, 1.154] | 0.780 | 0.922 | [0.758, 1.121] | 0.415 |
PAD (ref = none) | 0.922 | [0.767, 1.110] | 0.394 | 0.835 | [0.692, 1.006] | 0.060 |
Smoking (ref = none) | 1.005 | [0.869, 1.161] | 0.951 | 0.977 | [0.837, 1.141] | 0.769 |
Statin (ref = none) | 1.036 | [0.902, 1.190] | 0.615 | 0.914 | [0.780, 1.071] | 0.269 |
Variable | Estimate | CI | p-Value |
---|---|---|---|
AAA diameter | 0.999 | [0.985, 1.012] | 0.832 |
Thickness ILT | 1.010 | [1.000, 1.021] | 0.064 |
HDL cholesterol | 1.390 | [1.031, 1.875] | 0.034 |
Triglycerides | 1.152 | [1.029, 1.291] | 0.017 |
Smoking (ref = none) | 0.929 | [0.784, 1.102] | 0.402 |
CAD (ref = none) | 0.869 | [0.716, 1.055] | 0.160 |
PAD (ref = none) | 0.820 | [0.673, 0.999] | 0.053 |
T2D treatment (ref = none) | 1.225 | [0.999, 1.501] | 0.055 |
CCB (ref = none) | 0.863 | [0.718, 1.037] | 0.120 |
β-blocker (ref = none) | 1.313 | [1.087, 1.586] | 0.006 |
Univariable Analysis | Multivariate Analysis | |||||
---|---|---|---|---|---|---|
Variable | OR | CI | p-Value | OR | CI | p-Value |
Group (ref = varicose vein) | 0.978 | [0.834, 1.147] | 0.786 | 0.784 | [0.642, 0.958] | 0.019 |
Age | 1.007 | [1.000, 1.015] | 0.058 | 1.012 | [1.004, 1.020] | 0.005 |
Sex (ref = female) | 1.154 | [0.957, 1.391] | 0.135 | 1.350 | [1.083, 1.684] | 0.009 |
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Hamann, B.; Klimova, A.; Klotz, F.; Frank, F.; Jänichen, C.; Kapalla, M.; Sabarstinski, P.; Wolk, S.; Morawietz, H.; Poitz, D.M.; et al. Regulation of CD163 Receptor in Patients with Abdominal Aortic Aneurysm and Associations with Antioxidant Enzymes HO-1 and NQO1. Antioxidants 2023, 12, 947. https://doi.org/10.3390/antiox12040947
Hamann B, Klimova A, Klotz F, Frank F, Jänichen C, Kapalla M, Sabarstinski P, Wolk S, Morawietz H, Poitz DM, et al. Regulation of CD163 Receptor in Patients with Abdominal Aortic Aneurysm and Associations with Antioxidant Enzymes HO-1 and NQO1. Antioxidants. 2023; 12(4):947. https://doi.org/10.3390/antiox12040947
Chicago/Turabian StyleHamann, Bianca, Anna Klimova, Felicia Klotz, Frieda Frank, Christian Jänichen, Marvin Kapalla, Pamela Sabarstinski, Steffen Wolk, Henning Morawietz, David M. Poitz, and et al. 2023. "Regulation of CD163 Receptor in Patients with Abdominal Aortic Aneurysm and Associations with Antioxidant Enzymes HO-1 and NQO1" Antioxidants 12, no. 4: 947. https://doi.org/10.3390/antiox12040947
APA StyleHamann, B., Klimova, A., Klotz, F., Frank, F., Jänichen, C., Kapalla, M., Sabarstinski, P., Wolk, S., Morawietz, H., Poitz, D. M., Hofmann, A., & Reeps, C. (2023). Regulation of CD163 Receptor in Patients with Abdominal Aortic Aneurysm and Associations with Antioxidant Enzymes HO-1 and NQO1. Antioxidants, 12(4), 947. https://doi.org/10.3390/antiox12040947