Exploring the Association between Low-Density Lipoprotein Subfractions and Major Adverse Cardiovascular Outcomes—A Comprehensive Review
Abstract
:1. Introduction
2. Role of Low-Density Lipoproteins in Cardiovascular Disease
3. What We Know So Far
4. Genetics
5. Importance of Dosing LDL Subfractions and How It Impacts Overall Cardiovascular Risk
6. Future Directions
7. Current Limitations
8. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Plasmatic Lipoprotein | Density (g/mL) | Source | Composition (%) | Apolipoproteins | ||
---|---|---|---|---|---|---|
Lipid | Protein | Major | Others | |||
Chylomicrons | <0.95 | intestine | 98–99 | 1–2 | ApoB-48 | ApoA-I, A-II, A-IV, A-V |
VLDL | 0.95–1.006 | liver | 90–93 | 6–8 | ApoB-100 | ApoA-I, C-II, C-III, E, A-V |
IDL | 1.006–1.019 | catabolism of VLDL | 89 | 11 | ApoB-100 | ApoC-II, C-III, E |
LDL | 1.019–1.063 | catabolism of VLDL via IDL | 79 | 21 | ApoB-100 | - |
HDL | 1.063–1.210 | liver, intestine, catabolism of CM and VLDL | 67 | 33 | ApoA-I | ApoA-II, C-III, E, M |
Lp(a) | 1.006–1.125 | liver | 80 | 20 | Apo(a) | ApoB-100 |
sdLDL Properties | Sequence of Processes |
---|---|
Reduced binding to the LDL-C receptor | Increased residence time |
Increased penetrance of the arterial wall | Increased infiltration |
Increased affinity for arterial proteoglycans | Increased sequestration |
Increased susceptibility to oxidation | Increased oxidation |
Increased total cholesterol deposits | Accelerated atherosclerosis process |
Phenotype | Disorder | Genes Involved | Chromosome | References |
---|---|---|---|---|
High LDL-C | Familial hypercholesterolemia | LDLR | 19p13.3 | [14,15] |
Familial defective apolipoprotein B | APOB | 2p24-p23 | [14,15] | |
Autosomal dominant hypercholesterolemia type 3 (PCSK9 gain of function) | PCSK9 | 1p32.3 | [14,15] | |
Autosomal dominant hypercholesterolemia type 4 | STAP1 | 4q13.2 | [14,15] | |
Autosomal dominant hypercholesterolemia type 5 | APOE | 19q13 | [14,15] | |
Autosomal recessive hypercholesterolemia | LDLRAP1 (ARH) | 1p36-p35 | [14,15] | |
Cholesterol ester storage disease | LIPA | 10q21.31 | [14,15] | |
Sitosterolemia | ABCG5/ABCG8 | 2p21 | [14,15] | |
Low LDL-C | Abetalipoproteinemia (Bassen–Kornzweig syndrome) | MTTP | 4q24 | [13,14] |
Hypobetalipoproteinemia | APOB | 2p24-p23 | [13,14] | |
PCSK9 deficiency with low LDL-C levels (PCSK9 loss of function) | PCSK9 | 1p32.3 | [13,14] | |
Familial combined hypolipidemia (ANGPTL3 deficiency) | ANGPTL3 | 1p31.1-p22.3 | [13,14] | |
Chylomicron retention disease (Anderson disease) | SAR1B | 5p31.1 | [13,14] |
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Stanciulescu, L.A.; Scafa-Udriste, A.; Dorobantu, M. Exploring the Association between Low-Density Lipoprotein Subfractions and Major Adverse Cardiovascular Outcomes—A Comprehensive Review. Int. J. Mol. Sci. 2023, 24, 6669. https://doi.org/10.3390/ijms24076669
Stanciulescu LA, Scafa-Udriste A, Dorobantu M. Exploring the Association between Low-Density Lipoprotein Subfractions and Major Adverse Cardiovascular Outcomes—A Comprehensive Review. International Journal of Molecular Sciences. 2023; 24(7):6669. https://doi.org/10.3390/ijms24076669
Chicago/Turabian StyleStanciulescu, Laura Adina, Alexandru Scafa-Udriste, and Maria Dorobantu. 2023. "Exploring the Association between Low-Density Lipoprotein Subfractions and Major Adverse Cardiovascular Outcomes—A Comprehensive Review" International Journal of Molecular Sciences 24, no. 7: 6669. https://doi.org/10.3390/ijms24076669