|
|
||||||||
Review Article |
Dyslipoproteinemia and Atherosclerosis Research Unit, National Institute for Health and Medical Research, Hôpital de la Pitié, Paris, France
Abstract
Abstract I. Introduction A. Inflammation and Oxidative Stress in the Progression of Atherosclerosis II. Functional High-Density Lipoprotein A. Structure, Composition, and Heterogeneity B. Metabolism C. Biological Activities 1. Cholesterol Efflux Capacity. 2. Antioxidative Activity. 3. Anti-Inflammatory Activity. 4. Antiapoptotic, Vasodilatory, Antithrombotic, and Anti-Infectious Activities. III. Functionally Defective High-Density Lipoprotein in Dyslipidemic and Inflammatory States A. Altered High-Density Lipoprotein Composition and Enzymatic Activities in Dyslipidemic and Inflammatory States 1. Apolipoproteins. 2. Enzymes with Antioxidative and Anti-Inflammatory Properties. 3. Lipid Components. B. Abnormal High-Density Lipoprotein Metabolism in Dyslipidemic and Inflammatory States C. Impaired High-Density Lipoprotein Biological Activities in Dyslipidemic and Inflammatory States 1. Cholesterol Efflux Capacity. 2. Antioxidative Activity. 3. Anti-Inflammatory Activity. IV. Physiological Relevance of Defective High-Density Lipoprotein Function in Dyslipidemia and Metabolic Disease V. Functionally Defective Small, Dense High-Density Lipoprotein as a Therapeutic Target A. Cholesteryl Ester Transfer Protein Inhibitors B. Niacin C. Fibrates D. Statins E. Reconstituted High-Density Lipoprotein F. Apolipoprotein-Mimetic Peptides G. Combination Therapy VI. Conclusions
High-density lipoproteins (HDL) possess key atheroprotective biological properties, including cellular cholesterol efflux capacity, and anti-oxidative and anti-inflammatory activities. Plasma HDL particles are highly heterogeneous in physicochemical properties, metabolism, and biological activity. Within the circulating HDL particle population, small, dense HDL particles display elevated cellular cholesterol efflux capacity, afford potent protection of atherogenic low-density lipoprotein against oxidative stress and attenuate inflammation. The antiatherogenic properties of HDL can, however be compromised in metabolic diseases associated with accelerated atherosclerosis. Indeed, metabolic syndrome and type 2 diabetes are characterized not only by elevated cardiovascular risk and by low HDL-cholesterol (HDL-C) levels but also by defective HDL function. Functional HDL deficiency is intimately associated with alterations in intravascular HDL metabolism and structure. Indeed, formation of HDL particles with attenuated antiatherogenic activity is mechanistically related to core lipid enrichment in triglycerides and cholesteryl ester depletion, altered apolipoprotein A-I (apoA-I) conformation, replacement of apoA-I by serum amyloid A, and covalent modification of HDL protein components by oxidation and glycation. Deficient HDL function and subnormal HDL-C levels may act synergistically to accelerate atherosclerosis in metabolic disease. Therapeutic normalization of attenuated antiatherogenic HDL function in terms of both particle number and quality of HDL particles is the target of innovative pharmacological approaches to HDL raising, including inhibition of cholesteryl ester transfer protein, enhanced lipidation of apoA-I with nicotinic acid and infusion of reconstituted HDL or apoA-I mimetics. A preferential increase in circulating concentrations of HDL particles possessing normalized antiatherogenic activity is therefore a promising therapeutic strategy for the treatment of common metabolic diseases featuring dyslipidemia, inflammation, and premature atherosclerosis.
This article has been cited by other articles:
![]() |
M. J. Chapman, W. Le Goff, M. Guerin, and A. Kontush Cholesteryl ester transfer protein: at the heart of the action of lipid-modulating therapy with statins, fibrates, niacin, and cholesteryl ester transfer protein inhibitors Eur. Heart J., October 12, 2009; (2009) ehp399v1. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. N. Hoofnagle and J. W. Heinecke Lipoproteomics: using mass spectrometry-based proteomics to explore the assembly, structure, and function of lipoproteins J. Lipid Res., October 1, 2009; 50(10): 1967 - 1975. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. K. Schindhelm, L. P. van der Zwan, T. Teerlink, and P. G. Scheffer Myeloperoxidase: A Useful Biomarker for Cardiovascular Disease Risk Stratification? Clin. Chem., August 1, 2009; 55(8): 1462 - 1470. [Abstract] [Full Text] [PDF] |
||||
![]() |
Z. Zhang, G. Datta, Y. Zhang, A. P. Miller, P. Mochon, Y.-F. Chen, J. Chatham, G. M. Anantharamaiah, and C. R. White Apolipoprotein A-I mimetic peptide treatment inhibits inflammatory responses and improves survival in septic rats Am J Physiol Heart Circ Physiol, August 1, 2009; 297(2): H866 - H873. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. B. Massey, H. J. Pownall, S. Macha, J. Morris, M. R. Tubb, and R. A. G. D. Silva Mass spectrometric determination of apolipoprotein molecular stoichiometry in reconstituted high density lipoprotein particles J. Lipid Res., June 1, 2009; 50(6): 1229 - 1236. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Sattler and B. Levkau Sphingosine-1-phosphate as a mediator of high-density lipoprotein effects in cardiovascular protection Cardiovasc Res, May 1, 2009; 82(2): 201 - 211. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. Shao and J. W. Heinecke HDL, lipid peroxidation, and atherosclerosis J. Lipid Res., April 1, 2009; 50(4): 599 - 601. [Full Text] [PDF] |
||||
![]() |
M. L.E. MacDonald, M. van Eck, R. B. Hildebrand, B. W.C. Wong, N. Bissada, P. Ruddle, A. Kontush, H. Hussein, M. A. Pouladi, M. J. Chapman, et al. Despite Antiatherogenic Metabolic Characteristics, SCD1-Deficient Mice Have Increased Inflammation and Atherosclerosis Arterioscler Thromb Vasc Biol, March 1, 2009; 29(3): 341 - 347. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Catalano, Z. Julia, E. Frisdal, B. Vedie, N. Fournier, W. Le Goff, M. J. Chapman, and M. Guerin Torcetrapib Differentially Modulates the Biological Activities of HDL2 and HDL3 Particles in the Reverse Cholesterol Transport Pathway Arterioscler Thromb Vasc Biol, February 1, 2009; 29(2): 268 - 275. [Abstract] [Full Text] [PDF] |
||||
![]() |
J.-C. Fruchart, F. M Sacks, M. P Hermans, G. Assmann, W V. Brown, R. Ceska, M J. Chapman, P. M Dodson, P. Fioretto, H. N Ginsberg, et al. The Residual Risk Reduction Initiative: a call to action to reduce residual vascular risk in dyslipidaemic patients Diabetes and Vascular Disease Research, November 1, 2008; 5(4): 319 - 335. [Abstract] [PDF] |
||||
![]() |
J. Juarez-Rojas, A. Medina-Urrutia, R Posadas-Sanchez, E Jorge-Galarza, E Mendoza-Perez, N Caracas-Portilla, G Cardoso-Saldana, G Munoz-Gallegos, and C Posadas-Romero High-density lipoproteins are abnormal in young women with uncomplicated systemic lupus erythematosus Lupus, November 1, 2008; 17(11): 981 - 987. [Abstract] [PDF] |
||||
![]() |
G.F. Watts and D.C. Chan Of Mice and Men: Blowing Away the Cobwebs From the Mechanism of Action of Niacin on HDL Metabolism Arterioscler Thromb Vasc Biol, November 1, 2008; 28(11): 1892 - 1895. [Full Text] [PDF] |
||||
![]() |
L. Yvan-Charvet, C. Welch, T. A. Pagler, M. Ranalletta, M. Lamkanfi, S. Han, M. Ishibashi, R. Li, N. Wang, and A. R. Tall Increased Inflammatory Gene Expression in ABC Transporter-Deficient Macrophages: Free Cholesterol Accumulation, Increased Signaling via Toll-Like Receptors, and Neutrophil Infiltration of Atherosclerotic Lesions Circulation, October 28, 2008; 118(18): 1837 - 1847. [Abstract] [Full Text] [PDF] |
||||
![]() |
I. M. Heid, E. Boes, M. Muller, B. Kollerits, C. Lamina, S. Coassin, C. Gieger, A. Doring, N. Klopp, R. Frikke-Schmidt, et al. Genome-Wide Association Analysis of High-Density Lipoprotein Cholesterol in the Population-Based KORA Study Sheds New Light on Intergenic Regions Circ Cardiovasc Genet, October 1, 2008; 1(1): 10 - 20. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. Shao, G. Cavigiolio, N. Brot, M. N. Oda, and J. W. Heinecke Methionine oxidation impairs reverse cholesterol transport by apolipoprotein A-I PNAS, August 26, 2008; 105(34): 12224 - 12229. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Pirillo, P. Uboldi, C. Bolego, H. Kuhn, and A. L. Catapano The 15-Lipoxygenase-Modified High Density Lipoproteins 3 Fail to Inhibit the TNF-{alpha}-Induced Inflammatory Response in Human Endothelial Cells J. Immunol., August 15, 2008; 181(4): 2821 - 2830. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. R. Su, J. L. Blakemore, Y. Zhang, M. F. Linton, and S. Fazio Lentiviral Transduction of ApoAI Into Hematopoietic Progenitor Cells and Macrophages: Applications to Cell Therapy of Atherosclerosis Arterioscler Thromb Vasc Biol, August 1, 2008; 28(8): 1439 - 1446. [Abstract] [Full Text] [PDF] |
||||
![]() |
X. Moren, S. Deakin, M.-L. Liu, M.-R. Taskinen, and R. W. James HDL subfraction distribution of paraoxonase-1 and its relevance to enzyme activity and resistance to oxidative stress J. Lipid Res., June 1, 2008; 49(6): 1246 - 1253. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. T. Duong, G. L. Weibel, S. Lund-Katz, G. H. Rothblat, and M. C. Phillips Characterization and properties of pre{beta}-HDL particles formed by ABCA1-mediated cellular lipid efflux to apoA-I J. Lipid Res., May 1, 2008; 49(5): 1006 - 1014. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Ferns and V. Keti HDL-cholesterol modulation and its impact on the management of cardiovascular risk Ann Clin Biochem, March 1, 2008; 45(2): 122 - 128. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Levy High-density lipoprotein mass, cholesteryl ester transport protein, and macrophage reverse cholesterol transport: from the bedside back to the bench Cardiovasc Res, March 1, 2008; 77(4): 614 - 615. [Full Text] [PDF] |
||||
![]() |
M. Stahlman, P. Davidsson, I. Kanmert, B. Rosengren, J. Boren, B. Fagerberg, and G. Camejo Proteomics and lipids of lipoproteins isolated at low salt concentrations in D2O/sucrose or in KBr J. Lipid Res., February 1, 2008; 49(2): 481 - 490. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. J. Van Lenten, A. C. Wagner, M. Navab, G. M. Anantharamaiah, S. Hama, S. T. Reddy, and A. M. Fogelman Lipoprotein inflammatory properties and serum amyloid A levels but not cholesterol levels predict lesion area in cholesterol-fed rabbits J. Lipid Res., November 1, 2007; 48(11): 2344 - 2353. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. S. Pokrywka DEBATING CARDIOVASCULAR GOALS DOC News, October 1, 2007; 4(10): 5 - 5. [Full Text] |
||||
![]() |
M J. Chapman Metabolic syndrome and type 2 diabetes: lipid and physiological consequences Diabetes and Vascular Disease Research, September 1, 2007; 4(3_suppl): S5 - S8. [Abstract] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |