High-Density Lipoprotein in Metabolic Disorders and Beyond: An Exciting New World Full of Challenges and Opportunities
Abstract
:1. Introduction
2. HDL Proteome and Particle Functionality
3. HDL Lipidome and Particle Functionality
4. High-Density Lipoprotein and Plasma Triglyceride Levels
5. High-Density Lipoprotein in Type 2 Diabetes Mellitus
6. High-Density Lipoprotein and Adipose Tissue Metabolic Activity
7. High-Density Lipoprotein and Hepatic Triglyceride Deposition
8. High-Density Lipoprotein and Cancer
9. Current State of the Art in HDL Pharmaceuticals
Agent | Trial Status | Clinical Outcomes | Reference and NCT |
---|---|---|---|
Obicetrapib | Active, recruiting | Significant increase in HDL-C levels from 24 mg/dL to a maximum of 65 mg/dL. Significant increase in APOA1 by 50–60%. Significant decrease in APOB levels by 30–50% and Lp(a) levels by 30%. | [75] NCT05202509 |
Niaspan | Terminated (2012) | Significant increase in HDL-C levels by approximately 30%. Significant decrease in TG levels by 30%, LDL-C levels by 14%, (Lp(a)) levels by 32% and APOB levels by 9–39%. | [88] NCT00120289 |
D-4F | Completed (2017) | Binds to oxidized lipids more effectively than endogenous APOA1 and lowers the HDL inflammatory index. | [81,82]. |
CER-001 | Completed (2016) | Failed to demonstrate regression of atherosclerosis in patients with ACS already receiving statin therapy after 10 weekly infusions of CER-001. | [84] NCT02484378 |
CSL-111 | Completed (2008) | Did not reduce atherosclerotic plaque volume and led to elevated levels of liver enzymes. Its development was discontinued. | [86] NCT00225719 |
CSL-112 | Active, not recruiting | Well-tolerated in human trials. Increased HDL cholesterol efflux capacity. Currently assessing efficacy and safety. Results are expected by the end of 2023. | [87] NCT03473223 |
10. Opportunities for Novel Pharmaceuticals in the Gene-Editing Era
10.1. Examples of Gene-Editing-Based Pharmaceuticals in Cardiovascular Diseases
10.2. Challenges in the Development of Gene-Editing Pharmaceuticals
10.3. Opportunities for Gene-Editing Therapies for Treating Low and Dysfunctional HDL
11. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Zvintzou, E.; Xepapadaki, E.; Skroubis, G.; Mparnia, V.; Giannatou, K.; Benabdellah, K.; Kypreos, K.E. High-Density Lipoprotein in Metabolic Disorders and Beyond: An Exciting New World Full of Challenges and Opportunities. Pharmaceuticals 2023, 16, 855. https://doi.org/10.3390/ph16060855
Zvintzou E, Xepapadaki E, Skroubis G, Mparnia V, Giannatou K, Benabdellah K, Kypreos KE. High-Density Lipoprotein in Metabolic Disorders and Beyond: An Exciting New World Full of Challenges and Opportunities. Pharmaceuticals. 2023; 16(6):855. https://doi.org/10.3390/ph16060855
Chicago/Turabian StyleZvintzou, Evangelia, Eva Xepapadaki, George Skroubis, Victoria Mparnia, Katerina Giannatou, Karim Benabdellah, and Kyriakos E. Kypreos. 2023. "High-Density Lipoprotein in Metabolic Disorders and Beyond: An Exciting New World Full of Challenges and Opportunities" Pharmaceuticals 16, no. 6: 855. https://doi.org/10.3390/ph16060855
APA StyleZvintzou, E., Xepapadaki, E., Skroubis, G., Mparnia, V., Giannatou, K., Benabdellah, K., & Kypreos, K. E. (2023). High-Density Lipoprotein in Metabolic Disorders and Beyond: An Exciting New World Full of Challenges and Opportunities. Pharmaceuticals, 16(6), 855. https://doi.org/10.3390/ph16060855