A Novel Relative High-Density Lipoprotein Index to Predict the Structural Changes in High-Density Lipoprotein and Its Ability to Inhibit Endothelial–Mesenchymal Transition
Abstract
:1. Introduction
2. Results
2.1. TGF-β1 Induces Morphological Changes and EndoMT in EPCs That May Be Inhibited by HDL from Patients with rHDL Index Value Lower Than 2
2.2. TGF-β1-Induced Expression of EndoMT-Related Genes Was Regulated by HDL from Healthy Subjects and Patients with Lower rHDL Index
2.3. TGF-β1-Induced EndoMT Was Regulated by HDL from Healthy Subjects and Patients with Lower rHDL Index
2.4. HDL Regulates TGF-β1-Induced EndoMT via Smad- and Snail-Dependent Pathways
2.5. The Clinical Characteristics Did Not Differ between Patients with rHDL Index> and <2.
2.6. HDL from Patients with rHDL Index Value > 2 Had Higher Relative Abundance of Glycerolipid in Select Triglyceride (TG), Phosphatidylcholine (PC), and Phosphatidylinositol (PI) Species
3. Discussion
4. Materials and Methods
4.1. Ethics and Patient/Volunteer Demographics
4.2. Preparation of HDL
4.3. EPC Isolation and Cultivation
4.4. Immunofluorescence Staining
4.5. Real-Time Quantitative Polymerase Chain Reactions
4.6. Western Blot Analysis
4.7. DCF Assay for Identification of rHDL Index Value
4.8. Lipidomic Analysis
4.9. Lipid Identification
4.10. Statistics Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Patients with rHDL Index > 2 (n = 10) | Patients with rHDL Index < 2 (n = 10) | |
---|---|---|
Gender (Male/Female) | 5/5 | 5/5 |
Age (years) | 61.5 ± 5.7 | 65.9 ± 4.7 |
Body weight (kg) | 63.5 ± 15.7 | 65.7 ± 19.4 |
Body height (cm) | 167.2 ± 13.7 | 164.1 ± 19.2 |
Smoke (n, %) | 0, 0% | 0, 0% |
Alcohol drinking (n, %) | 0, 0% | 0, 0% |
Hypertension (n, %) | 8, 80% | 9, 90% |
Hypercholesterolemia (n, %) | 10,100% | 10,100% |
Diabetes mellitus (n, %) | 2, 20% | 3, 30% |
Peripheral vascular disease (n, %) | 0, 0% | 0, 0% |
Chronic obstructive pulmonary disease (n, %) | 0, 0% | 0, 0% |
Old stroke (n, %) | 0, 0% | 0, 0% |
Prior myocardial infarction (n, %) | 0, 0% | 0, 0% |
Autoimmune disorders | 0, 0% | 0, 0% |
Rheumatoid arthritis | 0, 0% | 0, 0% |
Asthma | 0, 0% | 0, 0% |
Chronic kidney deficiency | 0, 0% | 0, 0% |
Cancer | 0, 0% | 0, 0% |
NO | Formula | Description (Lipid) | Neutral Mass | m/z | Retention Time (min) | p Value | Fold Change | VIP Value |
---|---|---|---|---|---|---|---|---|
1 | C56H100O6 | TG(14:0/17:0/22:4)[iso6] | 840.721 | 1779.520 | 16.068 | 0.02 | 4.50 | 2.12 |
2 | C54H88O6 | TG(14:1/15:1/22:6)[iso6] | 832.658 | 853.642 | 11.413 | <0.01 | 2.19 | 1.70 |
3 | C55H98O6 | TG(14:0/16:0/22:4)[iso6] | 854.736 | 1710.471 | 16.414 | <0.01 | 2.67 | 2.08 |
4 | C53H100O6 | TG(14:0/14:1/22:0)[iso6] | 832.752 | 1683.528 | 16.697 | <0.01 | 2.18 | 1.98 |
5 | C53H98O6 | TG(14:0/14:1/22:1)[iso6] | 830.734 | 1679.501 | 16.414 | 0.01 | 2.77 | 1.82 |
6 | C50H83N3O15P2 | DG(18:1/20:4) | 1027.530 | 1060.566 | 4.086 | <0.01 | 2.37 | 1.75 |
7 | C34H68NO8P | PC(13:0/13:0) | 649.468 | 970.594 | 4.107 | 0.02 | 2.33 | 1.73 |
8 | C50H86NO8P | PC(20:1/22:6) | 859.609 | 896.564 | 10.776 | <0.01 | 4.08 | 1.7 |
9 | C48H100NO6P | PC(O-20:0/O-20:0) | 831.708 | 1653.485 | 16.393 | 0.05 | 3.15 | 1.82 |
10 | C36H74NO7P | PC(O-16:0/12:0) | 633.502 | 708.489 | 2.723 | 0.02 | 2.11 | 1.61 |
11 | C45H83O13P | PI(18:1/18:1) | 862.557 | 1743.145 | 9.821 | <0.01 | 2.70 | 2.08 |
12 | C42H83O8P | PA(20:0/19:0) | 746.583 | 1535.212 | 16.047 | 0.01 | 2.13 | 1.82 |
13 | C32H59O8P | PA(12:0/17:2(9Z,12Z)) | 602.395 | 616.413 | 4.598 | 0.02 | 2.14 | 1.51 |
14 | C26H53O9P | PG(20:0/0:0) | 540.343 | 1098.708 | 4.148 | 0.05 | 2.26 | 1.8 |
Gene | Forward Primer | Reverse Primer |
---|---|---|
CD31 | 5′-GTG AAG TCC GGA AAG CTG TCC-3′ | 5′-GGG CAG GTT CAT AAA TAA GTG CAC-3′ |
vWF | 5′-GGC TGC AGT ATG TCA AGG TGG-3′ | 5′-AGA GCC ATT GGT GCA GTG CAG-3′ |
VE-cadherin | 5′-AGA CAA TGG GAT GCC AAG TCB-3′ | 5′-AAG ATG AGC AGG GTG ATC ACT G-3′ |
calponin | 5′-ACC TCT ACG ACC CCA AGC TG-3′ | 5′-GAC ATT GAG CGT GTC GCA GTG-3′ |
αSMA | 5′-CTA TCA GGG GGC ACC ACT ATG-3′ | 5′-CCG ATC CAG ACA GAG TAT TTG CG-3′ |
vimentin | 5′-AGG CAA AGC AGG AGT CCA CTG A-3′ | 5′-ATC TGG CGT TCC AGG GAC TCAT -3′ |
GAPDH | 5′-TGC CCC CTC TGC TGA TGC C-3′ | 5′-CCT CCG ACG CCT GCT TCA CCA C-3′ |
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Lin, F.-Y.; Lin, Y.-W.; Shih, C.-M.; Lin, S.-J.; Tung, Y.-T.; Li, C.-Y.; Chen, Y.-H.; Lin, C.-Y.; Tsai, Y.-T.; Huang, C.-Y. A Novel Relative High-Density Lipoprotein Index to Predict the Structural Changes in High-Density Lipoprotein and Its Ability to Inhibit Endothelial–Mesenchymal Transition. Int. J. Mol. Sci. 2021, 22, 5210. https://doi.org/10.3390/ijms22105210
Lin F-Y, Lin Y-W, Shih C-M, Lin S-J, Tung Y-T, Li C-Y, Chen Y-H, Lin C-Y, Tsai Y-T, Huang C-Y. A Novel Relative High-Density Lipoprotein Index to Predict the Structural Changes in High-Density Lipoprotein and Its Ability to Inhibit Endothelial–Mesenchymal Transition. International Journal of Molecular Sciences. 2021; 22(10):5210. https://doi.org/10.3390/ijms22105210
Chicago/Turabian StyleLin, Feng-Yen, Yi-Wen Lin, Chun-Ming Shih, Shing-Jong Lin, Yu-Tang Tung, Chi-Yuan Li, Yung-Hsiang Chen, Cheng-Yen Lin, Yi-Ting Tsai, and Chun-Yao Huang. 2021. "A Novel Relative High-Density Lipoprotein Index to Predict the Structural Changes in High-Density Lipoprotein and Its Ability to Inhibit Endothelial–Mesenchymal Transition" International Journal of Molecular Sciences 22, no. 10: 5210. https://doi.org/10.3390/ijms22105210