The DOI matches its Crossref record; 226 of the 228 references it cites were found in a registry or an index.
HDL-targeted therapies: progress, failures and future
Abstract
Since the discovery in the 1970s that plasma levels of high-density lipoprotein cholesterol (HDL-C) are inversely associated with cardiovascular outcome, it has been postulated that HDL is anti-atherogenic and that increasing HDL-C levels is a promising therapeutic strategy. However, the recent failure of three orally active, HDL-C-raising agents has introduced considerable controversy, prompting the question of whether increasing the cholesterol cargo of HDL in a non-selective manner is an effective pharmacological approach for the translation of its atheroprotective and vasculoprotective activities. The interrelationships between HDL-C concentration, HDL particle number and levels of diverse HDL particle subpopulations of defined composition are complex, as are their relationships with reverse cholesterol transport and other anti-atherogenic functions. Such complexity highlights the incompleteness of our understanding of the biology of HDL particles. This article examines the HDL hypothesis in molecular and mechanistic terms, focusing on features that have been addressed, those that remain to be tested, and potential new targets for future pharmacological interventions.
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“whereas results from studies on treatment that increase HDL-cholesterol levels have so far been disappointing (41)”
From Effects of low-carbohydrate diets v. low-fat diets on body weight and cardiovascular risk factors: a meta-analysis of randomised controlled trials (2016) · cites this paper as [41]
In the citing paper
“Both in vitro and in vivo, these approaches can achieve a transient acceleration of RCT, sometimes without causing any significant change in HDL-C.”
From HDL cholesterol: reappraisal of its clinical relevance (2017) · cites this paper as [111]
In the citing paper
“Recent approaches primarily aim to optimise the function of HDL in RCT [110, 111].”
From HDL cholesterol: reappraisal of its clinical relevance (2017) · cites this paper as [111]
Citations
Cites
Detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III)
Grundy, S. M., Becker, D. M., Clark, L. T., Cooper, R., Denke, M. A., Howard, J. L., Hunninghake, D. B., Illingworth, D. R., Luepker, R. V., McBride, P. E., et al. (2002) · Civil War Book Review · Cited by 12,198
Yusuf, S., Hawken, S., Ôunpuu, S., Dans, T., Avezum, A., Lanas, F., McQueen, M., Budaj, A., Pais, P., Varigos, J., et al. (2004) · The Lancet · doi:10.1016/s0140-6736(04)17018-9 · Cited by 12,026
General Cardiovascular Risk Profile for Use in Primary Care: The Framingham Heart Study
D’Agostino, R. B., Vasan, R. S., Pencina, M. J., Wolf, P. A., Cobain, M., Massaro, J. M., & Kannel, W. B. (2008) · Circulation · doi:10.1161/circulationaha.107.699579 · Cited by 7,491
ESC/EAS Guidelines for the management of dyslipidaemias
Reiner, Ž., Catapano, A. L., De Backer, G., Graham, I., Taskinen, M.-R., Wiklund, O., Agewall, S., Alegria, E., Chapman, M. J., Durrington, P., et al. (2011) · European Heart Journal · doi:10.1093/eurheartj/ehr158 · Cited by 3,549
Self-citationEffects of torcetrapib in patients at high risk for coronary events
Barter, P. J., Caulfield, M., Eriksson, M., Grundy, S. M., Kastelein, J. J. P., Komajda, M., Lopez-Sendon, J., Mosca, L., Tardif, J.-C., Waters, D. D., et al. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa0706628 · Cited by 3,139
Niacin in Patients with Low HDL Cholesterol Levels Receiving Intensive Statin Therapy
The AIM-HIGH Investigators (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1107579 · Cited by 2,911
Effects of Combination Lipid Therapy in Type 2 Diabetes Mellitus
(2010) · New England Journal of Medicine · doi:10.1056/nejmoa1001282 · Cited by 2,837
MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins
Vickers, K. C., Palmisano, B. T., Shoucri, B. M., Shamburek, R. D., & Remaley, A. T. (2011) · Nature Cell Biology · doi:10.1038/ncb2210 · Cited by 2,741
PLASMA-HIGH-DENSITY-LIPOPROTEIN CONCENTRATION AND DEVELOPMENT OF ISCHÆMIC HEART-DISEASE
Miller, G. J., & Miller, N. E. (1975) · The Lancet · doi:10.1016/s0140-6736(75)92376-4 · Cited by 2,621
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2 of the 228 references couldn’t be matched to a known paper.
Research works printed but not linked: 3
- Voight, B. F. et al. Plasma HDL cholesterol and risk of myocardial infarction: a Mendelian randomisation study. Lancet 380, 572–580 (2012). This is the first study to test the causality of the relationship between CHD and HDL by genome-wide Mendelian randomization analysis. · DOI · Paper page
- Goffinet, M. et al. Anti-atherosclerotic effect of CER-001, an engineered HDL-mimetic, in the high-fat diet-fed LDLr knock-out mouse. Circulation Abstr. 126, A18667 (2012).
- Keyserling, C. H. et al. CER-001, a synthetic HDL-mimetic, safely mobilizes cholesterol in healthy dyslipidemic volunteers. Circulation Abstr. 124, A15525 (2011).
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Allayee, H. (2021) · Journal of Lipid Research · doi:10.1016/j.jlr.2021.100064 · Cited by 1
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Offermanns, S. (2020) · Springer eBooks · doi:10.1007/978-3-662-58304-3_43 · Cited by 1
Pappiani, C. (2016) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.6.2016.tde-02062016-145648 · Cited by 1
Kim, S. Y. (2019) · Deep Blue (University of Michigan) · Cited by 1
HDL-associated phosphatidylserine blunts myeloid activation and protects from atherosclerosisPreprint
Bernal, A., Hamid, A., Grao-Roldán, C., Scarpa, A., Sánchez, I. B., Nicolás-Ávila, J. Á., Pena-Couso, L., Yaghmour, M. H., Benguría, A., Rosado, A., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.11.26.689708 · Cited by 1
Modulation of vascular inflammation: cell type specific effects by ADAMs and HDL
van der Vorst, E. P. C. (2015) · doi:10.26481/dis.20150521ev
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Niemczyk, N. A. (2015) · Journal of Midwifery & Women s Health · doi:10.1111/jmwh.12281_1
T-cell specificity and regulation in atherosclerosis
Gisterå, A. (2015) · Figshare
Daikh, D., & Abramson, S. B. (2011) · Current Opinion in Rheumatology · doi:10.1097/bor.0b013e32834b1fb1
Prevention of Murine Atherosclerosis with Bempedoic Acid
Samsoondar, J. P. (2016) · Scholarship@Western (Western University)
Lipoproteomics : Environmental and Genetic Factors Affecting High-Density Lipoprotein (HDL)
Ljunggren, S. (2016) · Linköping University medical dissertations · doi:10.3384/diss.diva-131643
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Ronda, N., & Meroni, P. L. (2017) · Technical report · doi:10.1016/b978-0-12-803997-7.00007-7
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Targeted therapeutics in inflammatory atherosclerosis
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Combined bioactive approach over atherosclerosis risk biomarkers
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Domenecha, M., Estruch, R., Moreno, R., & Sánchez, M. A. (2017) · Revista Española de Cardiología Suplementos · doi:10.1016/s1131-3587(19)30012-3
Vásquez, M. N. B., Porchas-Quijada, M., Reyes-Castillo, Z., Pellegrini, O. R., Ochoa, E. A., Moya-Camarena, S. Y., & Montalvo-Corral, M. (2020) · Nutrición Hospitalaria · doi:10.20960/nh.03087
Ferreiro, A. O. R., Reyes, E. H., Labrada, R. R., Beatón, E. O., & Noa, R. L. (2021) · Orange Journal · doi:10.46502/issn.2710-995x/2020.3.03
Yin, L., Li, Y., Mente, A., Rangarajan, S., Ding, L., Hu, B., Yao, C., Wang, Y., Liu, X., Zhao, C., et al. (2021) · Research Square · doi:10.21203/rs.3.rs-566020/v1
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Sun, S., Huang, Y., Huang, Q., Liu, M., Feng, F., Ji, Z., Huang, L., Deng, W., & LI, T. W. (2021) · Research Square · doi:10.21203/rs.3.rs-960249/v1
Effect Of The ABCA1 Agonist CS-6253 On Amyloid β And Lipoproteins Metabolism In Cynomolgus Monkeys.Preprint
Noveir, S. D., Kerman, B. E., Xian, H., Meuret, C. J., Smadi, S., Martinez, A. E., Johansson, J., Zetterberg, H., Parks, B. A., Kuklenyik, Z., et al. (2022) · Research Square · doi:10.21203/rs.3.rs-1353214/v1
Chen, Y., Jiang, Y., Xia, A., Huang, Z., Liu, Z., Hong, C., Lin, Y., & Liu, X. (2023) · Research Square · doi:10.21203/rs.3.rs-2450913/v1
Formulation and Characterization of Bioactive Agent Containing Nanodisks
Lethcoe, K., Fox, C. A., Moh, I., Swackhamer, M., Karo, M., Lockhart, R., & Ryan, R. O. (2023) · Journal of Visualized Experiments · doi:10.3791/65145
Coronel, L., Miguel, M. I., Blasi, J., Marsal, S., D’Agostino, M. A., & Möller, I. (2023) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2023-eular.3169
Shetty, M., Shenoy, S., Kumar, N., Amuthan, A., Shenoy, G., Devi, V. G., Akshatha, A., & Mohandas Rao, K. G. (2023) · Research Journal of Pharmacy and Technology · doi:10.52711/0974-360x.2023.00979
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Gadade, D. D., Kulkarni, D. A., & Modi, A. (2025) · Elsevier eBooks · doi:10.1016/b978-0-323-90254-0.00003-9
Taradeh, M., Hardy, L. M., Dahik, V. D., Lhomme, M., Wang, H., Reydellet, C., Materne, C., Pukar, K. C., Bun, E., Clemessy, M., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.05.27.656492
Self-citationAhmed, I. U., Byrne, H. M., & Myerscough, M. R. (2025) · Mathematical Biosciences · doi:10.1016/j.mbs.2025.109496
Bridging the gap between CVD and COVID-19: the oxidized LDL hypothesis
Daher, J. (2025) · Frontiers in Medicine · doi:10.3389/fmed.2025.1588062
Noveir, S. D., Kerman, B. E., Xian, H., Meuret, C. J., Smadi, S., Martinez, A. E., Johansson, J., Zetterberg, H., Parks, B. A., Kuklenyik, Z., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20155656
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Plutzky, J., Virmani, R., & Schmidt, A. M. (2026) · Elsevier eBooks · doi:10.1016/b978-0-323-87862-3.00007-0
Li, Y., Wang, Y., Ma, R., Li, Z., Feng, Z., Kong, X., Zhou, Q., Guo, X., Yin, Y., Wu, Y., et al. (2026) · Food Chemistry · doi:10.1016/j.foodchem.2026.149072
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Ma, F. (2018) · theses.fr (ABES) · doi:10.70675/aec01babza8edz47a2zb4d4zc7c3be00b185
Hardy, L. M. (2019) · theses.fr (ABES) · doi:10.70675/2f5f4b0dzc92fz4cb4z9c5bzeb6d3fd3e791
Nouri, S., Niemelä, A., Nencini, R., Kolypetris, G., Niemi-Aro, T., Virtanen, S. I., Ollila, O. H. S., & Koivuniemi, A. (2026) · Communications Chemistry · doi:10.1038/s42004-026-02015-5
Jiang, L.-Y., Zhu, B.-Y., Zhou, L., Deng, D., Zhang, X.-Y., Chen, J., Jiang, P.-W., Wang, G.-R., Yang, Q.-M., Zhang, M.-H., et al. (2026) · Acta Pharmacologica Sinica · doi:10.1038/s41401-026-01847-0
Ashkar, H. A., Kovács, N., Veres-Balajti, I., Seres, I., Paragh, G., Ádány, R., & Pikó, P. (2026) · Biology · doi:10.3390/biology15131051
liu, L., Jiang, X., & Chen, Y. (2026) · Research Square · doi:10.21203/rs.3.rs-9947850/v1
Ragolia, L. (2026) · Molecular Biomedicine · doi:10.1186/s43556-026-00552-y
Metadata
- Authors
- Kingwell, B. A., Chapman, M. J., Kontush, A., & Miller, N. E.
- Affiliations
- Baker Heart and Diabetes Institute (AU)
- Inserm (FR)
- University of Oxford (GB)
- Corresponding author
- Kingwell, Bronwyn A.
- Venue
- Nature Reviews Drug Discovery
- Published
- 2014-05-23
- Volume
- 13
- Issue
- 6
- Pages
- 445-464
- ISSN
- 1474-1776 (ISSN-L)
- 1474-1784
- OpenAlex
- W1993577107
- Cited by
- 354
- References
- 228
- Citations by year
- 2026: 11 · 2025: 15 · 2024: 9 · 2023: 28 · 2022: 22 · 2021: 21 · 2020: 22 · 2019: 33 · 2018: 33 · 2017: 43 · 2016: 53 · 2015: 51 · 2014: 12
- FWCI
- 10.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Drug Discovery (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Paraoxonase enzyme and polymorphisms
- Keywords
- HDL cholesterol, HDL-targeted therapy, HDL particle number, reverse cholesterol transport, atheroprotection, cardiovascular disease, clinical trial failure
- MeSH terms
- Animals, Hypolipidemic Agents, Cardiovascular Diseases, Clinical Trials as Topic, Humans, Phosphatidylcholine-Sterol O-Acyltransferase, Lipoproteins, HDL, Models, Biological, Niacin, Recombinant Proteins, Drugs, Investigational, Up-Regulation, Apolipoprotein A-I, Cholesterol Ester Transfer Proteins, Molecular Targeted Therapy
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