Capacity of HDL to Efflux Cellular Cholesterol from Lipid-Loaded Macrophages Is Reduced in Patients with Familial Hypercholesterolemia
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Populations
2.2. Isolation and Compositional Characterization of HDL Subfraction
2.3. Cholesterol Efflux Assay
2.4. Statistics
3. Results
3.1. Patients’ Characteristics
3.2. Compositional Characterization of HDL Subfractions
3.3. The Percentage of Cholesterol Efflux Capacity of HDL Subfractions
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Variables | Familial Hypercholesterolemia (N = 34) | Healthy (N = 20) | p-Value | ||
---|---|---|---|---|---|
HEFH (N = 18) | HOFH (N = 16) | ||||
Sex | Male | 10 (55.6%) | 5 (31.3%) | 10 (50.0%) | 0.361 |
Female | 8 (44.4%) | 11 (68.8%) | 10 (50.0%) | ||
Age (y) | 33.61 ± 2.3 a | 14.0 ± 2.7 | 48.5 ± 1.9 a,b | <0.001 | |
TC (mmol/L) | 6.4 ± 0.5 a | 16.1 ± 1.2 | 4.9 ± 0.2 a | <0.001 | |
TG (mmol/L) | 1.2 ± 0.1 a | 2.3 ± 0.4 | 1.4 ± 0.1 a | <0.01 | |
HDL-C (mmol/L) | 1.6 ± 0.3 | 1.6 ± 0.2 | 1.3 ± 0.1 | 0.376 | |
LDL-C (mmol/L) | 4.3 ± 0.4 a | 11.9 ± 1.1 | 2.9 ± 0.1 a | <0.001 | |
HDL2 | PL/TP | 0.5 ± 0.0 a | 0.6 ± 0.0 | 0.6 ± 0.0 | <0.05 |
TC/TP | 0.3 ± 0.0 | 0.4 ± 0.0 b | 0.4 ± 0.0 b | <0.01 | |
HDL3 | PL/TP | 0.4 ± 0.0 | 0.5 ± 0.0 | 0.4 ± 0.0 | 0.080 |
TC/TP | 0.3 ± 0.0 | 0.3 ± 0.0 | 0.3 ± 0.0 | 0.734 | |
HDL2/HDL3 | 2.6 ± 0.1 a | 1.6 ± 0.2 | 2.4 ± 0.2 a | <0.001 |
Variables | Familial Hypercholesterolemia (N = 34) | p-Value | ||
---|---|---|---|---|
HEFH (N = 18) | HOFH (N = 16) | |||
FH score | 15.0 ± 0.0 | 25.6 ± 0.5 | <0.001 | |
Number of patients with xanthoma symptoms | 0.0% | 100.0% | <0.001 | |
Number of patients with MI history | 0% | 68.8% | <0.001 | |
Mutation (%) | Previously reported | 84.6% | 84.6% | 1.000 |
Novel | 15.4% | 15.4% | ||
Mutation type (%) | Missense | 44.4% | 50.0% | 1.000 |
Truncated | 27.8% | 25.0% | ||
Single nucleotide variant | 16.7% | 12.5% | ||
Single nucleotide polymorphism | 11.1% | 6.3% | ||
Missense, truncated | 0.0% | 6.3% | ||
Position of LDLR mutation (%) | Exon | 72.7% | 84.6% | 0.630 |
Intron | 27.3% | 12.5% | ||
Drugs consumption (%) | No drug | 66.7% | 6.2% | <0.01 |
Only statin | 33.3% | 18.8% | ||
Statin + ezetimibe | 0% | 75.0% |
Variables | Familial Hypercholesterolemia (N = 34) | Healthy (N = 20) | p-Value | |
---|---|---|---|---|
HEFH (N = 18) | HOFH (N = 16) | |||
HDL2 CEC (%) | 3.2 ± 0.1 a | 2.5 ± 0.1 | 3.3 ± 0.2 a | <0.001 |
HDL3 CEC (%) | 4.1 ± 0.2 a | 3.2 ± 0.2 | 4.5 ± 0.3 a | <0.001 |
HDL2 CEC/HDL-C | 2.3 ± 0.2 | 1.9 ± 0.3 | 2.6 ± 0.2 | 0.126 |
HDL3 CEC/HDL-C | 2.9 ± 0.3 | 2.5 ± 0.3 | 3.6 ± 0.3 a | <0.05 |
Variables | HOFH | HEFH | ||||||
---|---|---|---|---|---|---|---|---|
Unadjusted | Adjusted # | Unadjusted | Adjusted # | |||||
OR (95% CI) | p Value | OR (95% CI) | p Value | OR (95% CI) | p Value | OR (95% CI) | p Value | |
HDL2 CEC (%) | 0.091 (0.018–0.452) | <0.01 | 0.145 (0.018–1.175) | 0.071 | 0.864 (0.330–2.258) | 0.765 | 1.631 (0.386–6.887) | 0.505 |
HDL3 CEC (%) | 0.118 (0.035–0.399) | <0.01 | 0.306 (0.062–1.498) | 0.144 | 0.681 (0.345–1.343) | 0.268 | 0.763 (0.295–1.972) | 0.577 |
HDL2 CEC/HDL-C | 0.439 (0.194–0.991) | <0.05 | 1.149 (0.183–7.209) | 0.882 | 0.721 (0.321–1.623) | 0.430 | 1.187 (0.303–4.652) | 0.805 |
HDL3 CEC/HDL-C | 0.452 (0.240–0.852) | <0.05 | 0.860 (0.196–3.777) | 0.841 | 0.680 (0.240–1.250) | 0.214 | 0.856 (0.318–2.301) | 0.758 |
Variables | Unadjusted | Adjusted # | ||
---|---|---|---|---|
OR (95% CI) | p Value | OR (95% CI) | p Value | |
HDL2 CEC (%) | 0.004 (0.000–0.123) | <0.01 | 0.010 (0.000–0.533) | <0.05 |
HDL3 CEC (%) | 0.181 (0.055–0.595) | <0.01 | 0.385 (0.101–1.471) | 0.163 |
HDL2 CEC/HDL-C | 0.669 (0.300–1.490) | 0.325 | 1.005 (0.254–3.966) | 0.995 |
HDL3 CEC/HDL-C | 0.708 (0.383–1.311) | 0.272 | 1.013(0.317–3.241) | 0.982 |
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Ganjali, S.; Hosseini, S.; Rizzo, M.; Kontush, A.; Sahebkar, A. Capacity of HDL to Efflux Cellular Cholesterol from Lipid-Loaded Macrophages Is Reduced in Patients with Familial Hypercholesterolemia. Metabolites 2023, 13, 197. https://doi.org/10.3390/metabo13020197
Ganjali S, Hosseini S, Rizzo M, Kontush A, Sahebkar A. Capacity of HDL to Efflux Cellular Cholesterol from Lipid-Loaded Macrophages Is Reduced in Patients with Familial Hypercholesterolemia. Metabolites. 2023; 13(2):197. https://doi.org/10.3390/metabo13020197
Chicago/Turabian StyleGanjali, Shiva, Susan Hosseini, Manfredi Rizzo, Anatol Kontush, and Amirhossein Sahebkar. 2023. "Capacity of HDL to Efflux Cellular Cholesterol from Lipid-Loaded Macrophages Is Reduced in Patients with Familial Hypercholesterolemia" Metabolites 13, no. 2: 197. https://doi.org/10.3390/metabo13020197
APA StyleGanjali, S., Hosseini, S., Rizzo, M., Kontush, A., & Sahebkar, A. (2023). Capacity of HDL to Efflux Cellular Cholesterol from Lipid-Loaded Macrophages Is Reduced in Patients with Familial Hypercholesterolemia. Metabolites, 13(2), 197. https://doi.org/10.3390/metabo13020197