Translational Medicine in Uremic Vascular Calcification: Scavenging ROS Attenuates p-Cresyl Sulfate-Activated Caspase-1, NLRP3 Inflammasome and Eicosanoid Inflammation in Human Arterial Smooth Muscle Cells
Abstract
:1. Introduction
2. Results
2.1. CKD Patients Had an Increase in Circulating Levels of PCS and Medial Arterial Calcification
2.2. CKD Arteries Exhibited More Serious Elastic Lamina (EL) Disruption in Parallel with UVC Severity
2.3. Concordant with UVC Severity, CKD Arteries Manifested Enhanced Expressions of COX-2/cPLA-2 and 8-OHdG, Indicative of Eicosanoid Inflammation and Oxidative Injury
2.4. Higher Productions of Caspase-1, IL-1β and NLRP3 Inflammasome in CKD-UVC Arteries and PCS-Stimulated HASMC
2.5. ROS Scavenger Attenuates PCS-Triggered Coupling Expressions of COX-2/cPLA-2 in HASMC Model
2.6. ROS Scavenger Attenuates PCS-Triggered Expressions of Pro-Caspase-1 and NLRP3 in HASMC Model
3. Discussion
3.1. Pro-Oxidant PCS-Induced Internal EL Disruption as an Emerging Key Player of UVC Progression
3.2. Higher Circulating Levels of PCS Is in Parallel with UVC Severity, Oxidative EL Injury, Coupling Expressions of COX-2/cPLA-2, and ROS Scavenger Inhibits PCS-Induced Eicosanoid Inflammation
3.3. CKD-UVC Arteries Exert Higher Expressions of Caspase-1, IL-1β and NLRP3 Inflammasome, and ROS Scavenger Inhibits PCS-Activated Caspase-1 and NLRP3 Inflammasome
4. Materials and Methods
4.1. Patients and Arterial Specimens
4.2. Reagents for Immunohistochemistry (IHC) Staining and Cell Models
4.3. Cell and Treatments
4.4. RNA Isolation and Quantitative Real-Time PCR
4.5. Measurement of Circulating PCS Levels
4.6. Statistics
5. Conclusions
6. Patients
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Variables | Controls (n = 12) | CKD (n = 18) | p-Value |
---|---|---|---|
Age (years) | 67.3 ± 15.4 | 65.9 ± 12.8 | 0.78 |
Male, n (%) | 9 (75.0) | 13 (72.2) | 0.87 |
Diabetes, n (%) | 4 (33.3) | 14 (77.8) | <0.05 |
Cardiovascular disease, n (%) | 4 (33.3) | 7 (38.9) | 0.77 |
Heart failure, n (%) | 3 (25.0) | 5 (27.8) | 0.87 |
Anemia, n (%) | 5 (41.7) | 10 (55.6) | 0.48 |
Systolic blood pressure (mmHg) | 130.8 ± 34.0 | 143.1 ± 25.7 | 0.27 |
Diastolic blood pressure (mmHg) | 75.4 ± 16.1 | 82.9 ± 19.7 | 0.43 |
Blood urea nitrogen (mg/dL) | 18.0 ± 6.1 | 47.2 ± 23.8 | <0.01 |
Creatinine (mg/dL) | 0.9 ± 0.2 | 3.9 ± 2.4 | <0.01 |
eGFR (mL/min) b | 80.9 ± 13.8 | 22.6 ± 15.5 | <0.01 |
Sodium (mmol/L) | 135.1 ± 4.2 | 136.4 ± 5.4 | 0.46 |
Potassium (mmol/L) | 4.2 ± 0.7 | 3.9 ± 0.5 | 0.22 |
Glucose (mg/dL) | 151.6 ± 43.9 | 243.9 ± 113.2 | <0.05 |
Alanine aminotransferase (IU/L) | 29.2 ± 21.0 | 18.5 ± 11.7 | 0.10 |
Alkaline phosphatase (IU/L) | 125.6 ± 35.4 | 176.4 ± 60.9 | <0.05 |
Calcium (mg/dL) | 9.0 ± 0.4 | 8.8 ± 0.9 | 0.62 |
Phosphate (mg/dL) | 2.9 ± 0.4 | 5.0 ± 1.2 | <0.01 |
Calcium-phosphate product c | 26.1 ± 2.8 | 43.4 ± 9.7 | <0.01 |
p-cresyl sulfate | 1.2 ± 0.9 | 15.2 ± 8.1 | <0.01 |
Medial arterial calcification area (%) d | 2.1 ± 1.0 | 4.2 ± 1.9 | <0.01 |
p-Cresyl Sulfate (ug/mL) | Indoxyl Sulfate (ug/mL) | p-Value | |
---|---|---|---|
Creatinine (mg/dL) | 0.50 | 0.52 | <0.01 |
eGFR (ml/min) | 0.71 | 0.67 | <0.01 |
Blood urea nitrogen (mg/dL) | 0.42 | 0.41 | <0.05 |
Calcium-phosphate product | 0.76 | 0.70 | <0.01 |
Medial arterial calcification area (%) | 0.42 | 0.41 | <0.05 |
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Chang, J.-F.; Kuo, H.-L.; Liu, S.-H.; Hsieh, C.-Y.; Hsu, C.-P.; Hung, K.-C.; Wang, T.-M.; Wu, C.-C.; Lu, K.-C.; Lin, W.-N.; et al. Translational Medicine in Uremic Vascular Calcification: Scavenging ROS Attenuates p-Cresyl Sulfate-Activated Caspase-1, NLRP3 Inflammasome and Eicosanoid Inflammation in Human Arterial Smooth Muscle Cells. Life 2022, 12, 769. https://doi.org/10.3390/life12050769
Chang J-F, Kuo H-L, Liu S-H, Hsieh C-Y, Hsu C-P, Hung K-C, Wang T-M, Wu C-C, Lu K-C, Lin W-N, et al. Translational Medicine in Uremic Vascular Calcification: Scavenging ROS Attenuates p-Cresyl Sulfate-Activated Caspase-1, NLRP3 Inflammasome and Eicosanoid Inflammation in Human Arterial Smooth Muscle Cells. Life. 2022; 12(5):769. https://doi.org/10.3390/life12050769
Chicago/Turabian StyleChang, Jia-Feng, Hsiao-Ling Kuo, Shih-Hao Liu, Chih-Yu Hsieh, Chih-Ping Hsu, Kuo-Chin Hung, Ting-Ming Wang, Chang-Chin Wu, Kuo-Cheng Lu, Wei-Ning Lin, and et al. 2022. "Translational Medicine in Uremic Vascular Calcification: Scavenging ROS Attenuates p-Cresyl Sulfate-Activated Caspase-1, NLRP3 Inflammasome and Eicosanoid Inflammation in Human Arterial Smooth Muscle Cells" Life 12, no. 5: 769. https://doi.org/10.3390/life12050769