Uremic Apelin and Leucocytic Angiotensin-Converting Enzyme 2 in CKD Patients
Abstract
:1. Introduction
2. Results
2.1. Levels of Serum APLN Are Elevated in CKD3–5 and HD Patients and Correlate with Leucocytic Expression of APLNR and ACE2
2.2. Leucocytic Organic Anion Transporter SLCO2B1 Is Increased in Uremic Patients and Correlates with Diminished ACE2
2.3. Uremic Toxins Mediated Increase of Intracellular miR-421 Leads to Monocytic Silencing of ACE2 and Elevation of Pro-Inflammatory TNFa and IL-6
2.4. Uremic Milieu and APLN Peptides Increase the Expression of APLNR In Vitro
2.5. APLN Peptides Dramatically Increase the Expression of ACE2 and APLNR
2.6. Uraemia-Mediated Decrease in Monocytic ACE2 Could Be Partially Re-Induced with APLN Peptides
2.7. APLN Peptides Decrease the Expression of TNFa and IL-6 In Vitro as well as AngII and Ang1–7 Receptors
2.8. APLN Peptides Affect Transmigration and Adhesion of the Cells In Vitro
3. Discussion
4. Materials and Methods
4.1. Patients, RNA, and Serum Isolation
4.2. Serum APLN Levels
4.3. Cell Culture and Treatments of THP-1 Monocytes
4.4. Real Time PCR
4.5. Transmigration Assay
4.6. Adhesion Assay
4.7. Statistics
4.8. Limitations
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Parameters | NP (n = 32) | HD (n = 66) | CKD3–5 (n = 24) |
---|---|---|---|
Age (years) | 53.1 ± 6.84 | 63.02 ± 14.69 | 74.54 ± 10.72 |
Male/female | 8/24 | 44/22 | 8/16 |
Body mass index (kg/m2) | 24.50 ± 4.01 | 25.91 ± 4.73 | 28.56 ± 6.42 |
Hypertension (%) | 6.25 | 92.42 | 91.67 |
Diabetes (%) | 3.12 | 37.88 | 33.3 |
Ever smoker (%) | 46.88 | 57.58 | 41.67 |
Dialysis vintage HD (years) | 0 | 8.40 ± 5.11 | 0 |
History of cardiovascular disease (%) | 0 | 45.45 | 66.67 |
Creatinine (µmol/L) | 69.88 ± 12.94 | 763.58 ± 290.65 | 157.71 ± 67.28 |
Urea (mmol/L) | 4.54 ± 1.36 | 21.57 ± 6.95 | 15.33 ± 17.48 |
Albumin (g/dL) | 4.10 ± 0.30 | 3.88 ± 0.48 | N/A |
C-reactive protein (mg/L) | 1.73 ± 1.36 | 13.38 ± 23.84 | 11.03 ± 15.13 |
Leucocytes (G/L) | 6.15 ± 1.59 | 7.69 ± 3.44 | 6.71 ± 1.75 |
Monocytes (% leukocytes) | 8.22 ± 2.41 | 8.48 ± 2.99 | N/A |
HDL (mmol/L) | 1.78 ± 0.45 | 1.32 ± 0.63 | N/A |
LDL (mmol/L) | 2.42 ± 0.92 | 3.78 ± 0.86 | N/A |
Cholesterol (mmol/L) | 6.17 ± 0.83 | 4.37 ± 1.26 | N/A |
Triglyceride (mmol/L) | 1.40 ± 1.14 | 2.20 ± 2.36 | N/A |
25(OH) vit. D (%) | 0 | 90.91 | 25.00 |
ACEi (%) | 0 | 24.24 | 33.33 |
ARB (%) | 0 | 42.42 | 45.83 |
β-blockers (%) | 0 | 77.27 | 75.00 |
Statins (%) | 0 | 37.88 | 58.33 |
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Trojanowicz, B.; Ulrich, C.; Girndt, M. Uremic Apelin and Leucocytic Angiotensin-Converting Enzyme 2 in CKD Patients. Toxins 2020, 12, 742. https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12120742
Trojanowicz B, Ulrich C, Girndt M. Uremic Apelin and Leucocytic Angiotensin-Converting Enzyme 2 in CKD Patients. Toxins. 2020; 12(12):742. https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12120742
Chicago/Turabian StyleTrojanowicz, Bogusz, Christof Ulrich, and Matthias Girndt. 2020. "Uremic Apelin and Leucocytic Angiotensin-Converting Enzyme 2 in CKD Patients" Toxins 12, no. 12: 742. https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12120742