The High Density Lipoprotein Cholesterol Hypothesis Revisited

Anna Meiliana, Nurrani Mustika Dewi, Andi Wijaya

Abstract


BACKGROUND: The strong inverse association of plasma levels of high-density lipoprotein cholesterol (HDL-C) with coronary heart disease (CHD) found in human epidemiological studies led to the development of the ‘HDL-C hypothesis’, which posits that intervention to raise HDL-C will result in reduced risk of CHD. However, recent evidence has raised doubts about the hypotheses that elevating HDL-C is necessarily therapeutic. Genetic variations that associate with altered HDL-C do not strongly associate with altered cardiovascular disease risk.

CONTENT: HDL-mediated cholesterol efflux from macrophage foam cells or measurements of the flux of cholesterol from macrophages to the liver and feces seem to correlate better with atherosclerotic burden than with HDL-C levels. Thus, it may be time to modify the HDL-C hypothesis to the ‘HDL flux hypothesis’, where intervention to promote cholesterol efflux and reverse cholesterol transport will reduce CHD risk, regardless of whether it affects plasma HDL-C levels. A deeper understanding of the complex biology of HDL metabolism and its relationship to reverse cholesterol transport and atherothromobotic events is urgently needed. This might lead to biomarkers of HDL flux and functionality that are more informative than simple measurements of HDL-C levels.

SUMMARY: It is now clear from recent clinical trial and genetic studies that some approaches to raising HDL-C levels may have no effect on CHD. This suggests the need to evaluate HDL-C-raising therapies in different clinical populations, as well as therapies targeted toward HDL flux and function rather than simply HDL-C elevation. Perhaps moving from a focus on the HDL-C hypothesis to a focus on the HDL flux hypothesis will permit a biologically based reassessment of the optimal therapeutic approach to targeting HDL for reduction in cardiovascular risk.

KEYWORDS: reverse cholesterol transport, cholesterol efflux capacity, HDL dysfunction, HDL particle size, HDL lipidomics, HDL proteomics


Full Text:

PDF

References


Rosenson RS. The high-density lipoprotein puzzle. Why classic epidemiology, genetic epifemiology, and clinical trials conflict? Arterioscler Vasc Thromb Biol. 2016; 36: 777-82, CrossRef.

Boden WE, Probsteld JL, Anderson T, Chaitman BR, Desvignes-Nickens P, Koprowicz K, et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011; 365: 2255-67, CrossRef.

Landray MJ, Haynes R, Hopewell JC, Parish S, Aung T, Tomson J, et al. Effects of extended-release niacin with laropiprant in high-risk patients. N Engl J Med. 2014; 371: 203-12, CrossRef.

Anderson TJ, Boden WE, Desvigne-Nickens P, Fleg JL, Kashyap ML, McBride R, et al. Safety profile of extended-release niacin in the AIM-HIGH trial. N Engl J Med. 2014; 371: 288-90, CrossRef.

Schwartz GG, Olsson AG, Abt M, Ballantyne CM, Barter PJ, Brumm J, et al. Effects of dalcetrapib in patients with a recent acute coronary syndrome. N Engl J Med. 2012; 367: 2089-99, CrossRef.

Barter PJ, Cauleld M, Eriksson M, Grundy SM, Kastelein JJ, Komajda M, et al. Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med. 2007; 357: 2109-22, CrossRef.

PRNewswire [Internet]. Lilly Provides Update on Evacetrapib Phase 3 Trial [updated 2015 Jul 27; cited 2018 Jan 12]. Available from: https://www.prnewswire.com/.

Nicholls SJ, Ruotolo G, Brewer HB, Kane JP, Wang MD, Krueger KA, et al. Cholesterol efflux capacity and pre-beta-1 HDL concentrations are increased in dyslipidemic patients treated with evacetrapib. J Am Coll Cardiol. 2015; 66: 2201-10, CrossRef.

Rosenson RS, Brewer HB Jr. New challenges for HDL-modifying therapies as a strategy to lower cardiovascular disease events in statin-treated patients. Cardiovasc Drugs Ther. 2015; 29: 1-3, CrossRef.

Rosenson RS, Brewer HB Jr, Chapman MJ, Fazio S, Hussain MM, Kontush A, et al. HDL measures, particle heterogeneity, proposed nomenclature, and relation to atherosclerotic cardiovascular events. Clin Chem. 2011; 57: 392-410, CrossRef.

Rosenson RS, Brewer HB Jr, Davidson WS, Fayad ZA, Fuster V, Goldstein J, et al. Cholesterol efflux and atheroprotection: advancing the concept of reverse cholesterol transport. Circulation. 2012; 125: 1905-19, CrossRef.

Camont L, Lhomme M, Rached F, Le Goff W, Nègre-Salvayre A, Salvayre R, et al. Small, dense high-density lipoprotein-3 particles are enriched in negatively charged phospho-lipids: relevance to cellular cholesterol efflux, antioxidative, antithrombotic, anti-inflammatory, and antiapoptotic functionalities. Arterioscler Thromb Vasc Biol. 2013; 33: 2715-23, CrossRef.

Rohatgi A, Khera A, Berry JD, Givens EG, Ayers CR, Wedin KE, et al. HDL cholesterol efflux capacity and incident cardiovascular events. N Engl J Med. 2014; 371: 2383-93, CrossRef.

Saleheen D, Scott R, Javad S, Zhao W, Rodrigues A, Picataggi A, et al. Association of HDL cholesterol efflux capacity with incident coronary heart disease events: a prospective case-control study. Lancet Diabetes Endocrinol. 2015; 3: 507-13, CrossRef.

Rosenson RS, Brewer HB Jr, Ansell B, Barter P, Chapman MJ, Heinecke JW, et al. Translation of high-density lipoprotein function into clinical practice: current prospects and future challenges. Circulation. 2013; 128: 1256-67, CrossRef.

Rosenson RS, Brewer HB Jr, Ansell BJ, Barter P, Chapman MJ, Heinecke JW, et al. Dysfunctional HDL and atherosclerotic cardiovascular disease. Nat Rev Cardiol. 2016; 13: 48-60, CrossRef.

Huang Y, DiDonato JA, Levison BS, Schmitt D, Li L, Wu Y, et al. An abundant dysfunctional apolipoprotein A1 in human atheroma. Nat Med. 2014; 20: 193-203, CrossRef.

Shao B, Tang C, Sinha A, Mayer PS, Davenport GD, Brot N, et al. Humans with atherosclerosis have impaired ABCA1 cholesterol efflux and enhanced high-density lipoprotein oxidation by myeloperoxidase. Circ Res. 2014; 114: 1733-42, CrossRef.

Rader DJ, Alexander ET, Weibel GL, Billheimer J, Rothblat GH. The role of reverse cholesterol transport in animals and humans and relationship to atherosclerosis. J Lipid Res. 2009; 50(Suppl): S189-94, CrossRef.

Rader DJ, Tall AR. Is it time to revise the HDL cholesterol hypothesis? Nat Med 2012; 18: 1344-6, CrossRef.

Shah AS, Tan L, Long JL, Davidson WS. Proteomic diversity of high density lipoproteins: our emerging understanding of its importance in lipid transport and beyond. J Lipid Res. 2013; 54: 2575-85, CrossRef.

Toth PP, Barter PJ, Rosenson RS, Boden WE, Chapman MJ, Cuchel M, et al. High-density lipoproteins: a consensus statement from the National Lipid Association. J Clin Lipidol. 2013; 7: 484-525, CrossRef.

Heinecke JW. Small HDL promotes cholesterol efflux by the ABCA1 pathway in macrophages: implications for therapies targeted to HDL. Circ Res. 2015; 116: 1101-3, CrossRef.

Otvos JD. Measurement of lipoprotein subclass profiles by nuclear magnetic resonance spectroscopy. Clin Lab. 2002; 48 : 171-80, PMID.

Caulfield MP, Li S, Lee G, Blanche PJ, Salameh WA, Benner WH, et al. Direct determination of lipoprotein particle sizes and concentrations by ion mobility analysis. Clin Chem. 2008; 54: 1307-16, CrossRef.

Hutchins PM, Ronsein GE, Monette JS, Pamir N, Wimberger J, He Y, et al. Quantification of HDL particle concentration by calibrated ion mobility analysis. Clin Chem. 2014; 60: 1393-401, CrossRef.

Ronsein GE, Heinecke JW. Time to ditch HDL-C as a measure of HDL function? Curr Opin Lipidol. 2017; 28: 414-8, CrossRef.

Vaisar T, Tang C, Babenko I, Hutchins P, Wimberger J, Suffredini AF, et al. Inflammatory remodeling of the HDL proteome impairs cholesterol efflux capacity. J Lipid Res. 2015; 56: 1519-30, CrossRef.

Ronsein GE, Reyes-Soffer G, He Y, Oda M, Ginsberg H, Heinecke JW. Targeted proteomics identifies paraoxonase/arylesterase 1 (PON1) and apolipoprotein Cs as potential risk factors for hypoalphalipoproteinemia in diabetic subjects treated with fenofibrate and rosiglitazone. Mol Cell Proteomics. 2016; 15: 1083-93, CrossRef.

Marsillach J, Becker JO, Vaisar T, Hahn BH, Brunzell JD, Furlong CE, et al. Paraoxonase-3 is depleted from the high-density lipoproteins of autoimmune disease patients with subclinical atherosclerosis. J Proteome Res. 2015; 14: 2046-54, CrossRef.

Gordon SM, Davidson WS, Urbina EM, Dolan LM, Heink A, Zang H, et al. The effects of type 2 diabetes on lipoprotein composition and arterial stiffness in male youth. Diabetes. 2013; 62: 2958-67, CrossRef.

Ronsein GE, Pamir N, von Haller PD, Kim DS, Oda MN, Jarvik GP, et al. Parallel reaction monitoring (PRM) and selected reaction monitoring (SRM) exhibit comparable linearity, dynamic range and precision for targeted quantitative HDL proteomics. J Proteomics. 2015; 113: 388-99, CrossRef.

Henderson CM, Vaisar T, Hoofnagle AN. Isolating and quantifying plasma HDL proteins by sequential density gradient ultracentrifugation and targeted proteomics. Methods Mol Biol. 2016; 1410: 105-20, CrossRef.

Khera AV, Cuchel M, de la Llera-Moya M, Rodrigues A, Burke MF, Jafri K, et al. Cholesterol efflux capacity, high-density lipoprotein function, and atherosclerosis. New Engl J Med. 2011; 364: 127-35, CrossRef.

Voight BF, Peloso GM, Orho-Melander M, Frikke-Schmidt R, Barbalic M, Jensen MK, et al. Plasma HDL cholesterol and risk of myocardial infarction: a mendelian randomisation study. Lancet. 2012; 380: 572-80, CrossRef.

von Eckardstein A, Rohrer L. HDLs in crises. Curr Opin Lipidol. 2016; 27: 264-73, CrossRef.

Chang TI, Streja E, Moradi H. Could high-density lipoprotein cholesterol predict increased cardiovascular risk? Curr Opin Endocrinol Diabetes Obes. 2017; 24: 140-7, CrossRef.

Fazio S, Pamir N. HDL particle size and functional heterogeneity. Circ Res. 2016; 119: 704-7, CrossRef.

Camont L, Chapman MJ, Kontush A. Biological activities of HDL subpopulations and their relevance to cardiovascular disease. Trends Mol Med. 2011; 17: 594-603, CrossRef.

Kuller L, Arnold A, Tracy R, Otvos J, Burke G, Psaty B, et al. Nuclear magnetic resonance spectroscopy of lipoproteins and risk of coronary heart disease in the Cardiovascular Health Study. Arterioscler Thromb Vasc Biol. 2002; 22: 1175-80, CrossRef.

Rosenson RS, Otvos JD, Freedman DS. Relations of lipoprotein subclass levels and low-density lipoprotein size to progression of coronary artery disease in the Pravastatin Limitation of Atherosclerosis in the Coronary Arteries (PLAC-I) trial. Am J Cardiol. 2002; 90: 89-94, CrossRef.

Garvey WT, Kwon S, Zheng D, Shaughnessy S, Wallace P, Hutto A, et al. Effects of insulin resistance and type 2 diabetes on lipoprotein subclass particle size and concentration determined by nuclear magnetic resonance. Diabetes Metab Res Rev. 2003; 52: 453-62, CrossRef.

Festa A, Williams K, Hanley AJG, Otvos JD, Goff DC, Wagenknecht LE, et al. Nuclear magnetic resonance lipoprotein abnormalities in prediabetic subjects in the insulin resistance atherosclerosis study. Circulation. 2005; 111: 3465-72, CrossRef.

Goff DC Jr, D’Agostino RB Jr, Haffner SM, Otvos JD. Insulin resistance and adiposity influence lipoprotein size and subclass concentrations. Results from the insulin resistance atherosclerosis study. Metabolism. 2005; 54: 264-70, CrossRef.

Kathiresan S, Otvos JD, Sullivan LM, Keyes MJ, Schaefer EJ, Wilson PW, et al. Increased small low-density lipoprotein particle number: a prominent feature of the metabolic syndrome in the Framingham Heart Study. Circulation. 2006; 113: 20-9, CrossRef.

Otvos JD, Collins D, Freedman DS, Shalaurova I, Schaefer EJ, Mcnamara JR, et al. Low-density lipoprotein and high-density lipoprotein particle subclasses predict coronary events and are favorably changed by gemfibrozil therapy in the Veterans Affairs High-Density Lipoprotein Intervention Trial. Circulation. 2006; 113: 1556-63, CrossRef.

Mora S, Szklo M, Otvos JD, Greenland P, Psaty BM, Goff DC, et al. LDL particle subclasses. LDL particle size, and carotid atherosclerosis in the Multi-Ethnic Study of Atherosclerosis (MESA). Atherosclerosis. 2007; 192: 211-7, CrossRef.

Mora S, Otvos JD, Rifai N, Rosenson RS, Buring JE, Ridker PM. Lipoprotein particle profiles by nuclear magnetic resonance compared with standard lipids and apolipoproteins in predicting incident cardiovascular disease in women. Circulation. 2009; 119: 931-9, CrossRef.

van der Steeg WA, Holme I, Boekholdt SM, Larsen ML, Lindahl C, Stroes ES, et al. High-density lipoprotein cholesterol, high-density lipoprotein particle size, and apolipoprotein A-I: significance for cardiovascular risk: the IDEAL and EPIC-Norfolk studies. J Am Coll Cardiol. 2008; 51: 634-42, CrossRef.

El Harchaoui K, Arsenault BJ, Franssen R, Despres JP, Hovingh GK, Stroes ES, et al. High-density lipoprotein particle size and concentration and coronary risk. Ann Intern Med. 2009; 150: 84-93, CrossRef.

Kontush A. HDL particle number and size as predictors of cardiovascular disease. Front Pharmacol. 2015; 6: 218. Doi: 10.3389/fphar.2015.00218, CrossRef.

Kontush A, Lhomme M, Chapman MJ. Unraveling the complexities of the HDL lipidome. J Lipid Res. 2013; 54: 2950-63, CrossRef.

Pirillo A, Norata GD, Catapano AL. High-density lipoprotein subfractions – What the clinicians need to know. Cardiology. 2013; 123: 116-25, CrossRef.

Norata GD, Pirillo A, Ammirati E, Catapano AL. Emerging role of high density lipoproteins as a player in the immune system. Atherosclerosis. 2012; 220: 11–21, CrossRef.

Drew BG, Rye KA, Duffy SJ, Barter P, King-well BA. The emerging role of HDL in glucose metabolism. Nat Rev Endocrinol. 2012; 8: 237-45, CrossRef.

Singh SA, Andraski AB, Pieper B, Goh W, Mendivil CO, Sacks FM, et al. Multiple apolipoprotein kinetics measured in human HDL by high-resolution/accurate mass parallel reaction monitoring. J Lipid Res. 2016; 57: 714-28, CrossRef.

Singh SA, Miyosawa K, Aikawa M. Mass spectrometry meets the challenge of understanding the complexity of the lipoproteome: recent findings regarding proteins involved in dyslipidemia and cardiovascular disease. Exp Rev Proteomics. 2015; 12: 519-32, CrossRef.

Singh SA, Aikawa M. Unbiased and targeted mass spectrometry for the HD: proteome. Curr Opin Lipidol. 2017; 28: 68. doi: 10.1097/mol.0000000000000374, CrossRef.

Rye KA, Barter PJ. Regulation of high-density lipoprotein metabolism. Circ Res. 2014; 114: 143-56, CrossRef.

Stoffel W, Krüger E, Deutzmann R. Cell-free translation of human liver apolipoprotein AI and AII mRNA. Processing of primary translation products. Hoppe Seylers Z Physiol Chem. 1983; 364: 227-37, CrossRef.

Chau P, Fielding PE, Fielding CJ. Bone morphogenetic protein-1 (BMP-1) cleaves human proapolipoprotein A1 and regulates its activation for lipid binding. Biochemistry. 2007; 46: 8445-50, CrossRef.

Zhu J, Gardner J, Pullinger CR, Kane JP, Thompson JF, Francone OL. Regulation of apoAI processing by procollagen C-proteinase enhancer-2 and bone morphogenetic protein-1. J Lipid Res. 2009; 50: 1330-9, CrossRef.

Gillard BK, Lin HY, Massey JB, Pownall HJ. Apolipoproteins A-I, A-II and E are independently distributed among intracellular and newly secreted HDL of human hepatoma cells. Biochim Biophys Acta. 2009; 1791: 1125-32, CrossRef.

Kiss RS, McManus DC, Franklin V, Tan WL, McKenzie A, Chimini G, Marcel YL. The lipidation by hepatocytes of human apolipoprotein A-I occurs by both ABCA1-dependent and -independent pathways. J Biol Chem. 2003; 278: 10119-27, CrossRef.

Ji A, Wroblewski JM, Cai L, de Beer MC, Webb NR, van der Westhuyzen DR. Nascent HDL formation in hepatocytes and role of ABCA1, ABCG1, and SR-BI. J Lipid Res. 2012; 53: 446-55, CrossRef.

Maric J, Kiss RS, Franklin V, Marcel YL. Intracellular lipidation of newly synthesized apolipoprotein A-I in primary murine hepatocytes. J Biol Chem. 2005; 280: 39942-9, CrossRef.

Nagata KO, Nakada C, Kasai RS, Kusumi A, Ueda K. ABCA1 dimermonomer interconversion during HDL generation revealed by single- molecule imaging. Proc Natl Acad Sci USA. 2013; 110: 5034-9, CrossRef.

Phillips MV. Molecular mechanisms of cellular cholesterol efflux. J Biol Chem. 2014; 289: 24020-9, CrossRef.

Kimura T, Sato K, Malchinkhuu E, Tomura H, Tamama K, Kuwabara A, et al. High-density lipoprotein stimulates endothelial cell migration and survival through sphingosine 1-phosphate and its receptors. Arterioscler Thromb Vasc Biol. 2003; 23: 1283-8, CrossRef.

Nofer JR, van der Giet M, Tölle M, Wolinska I, von Wnuck Lipinski K, Baba HA, et al. HDL induces NO-dependent vasorelaxation via the lysophospholipid receptor S1P3. J Clin Invest. 2004; 113: 569-81, CrossRef.

Christoffersen C, Obinata H, Kumaraswamy SB, Galvani S, Ahnström J, Sevvana M, et al. Endothelium-protective sphingosine-1-phosphate provided by HDL- associated apolipoprotein M. Proc Natl Acad Sci USA. 2011; 108: 9613-8, CrossRef.

Galvani S, Sanson M, Blaho VA, Swendeman SL, Obinata H, Conger H, et al. HDL-bound sphingosine 1-phosphate acts as a biased agonist for the endothelial cell receptor S1P1 to limit vascular inflammation. Sci Signal. 2015; 8: ra79. doi: 10.1126/scisignal.aaa2581, CrossRef.

Wilkerson BA, Grass GD, Wing SB, Argraves WS, Argraves KM. Sphingosine 1-phosphate (S1P) carrier-dependent regulation of endothelial barrier: high density lipoprotein (HDL)-S1P prolongs endothelial barrier enhancement as compared with albumin-S1P via effects on levels, traf cking, and signaling of S1P1. J Biol Chem. 2012; 287: 44645-53. CrossRef.

Blaho VA, Galvani S, Engelbrecht E, Liu C, Swendeman SL, Kono M, et al. HDL-bound sphingosine-1-phosphate restrains lymphopoiesis and neuroinflammation. Nature. 2015; 523: 342-6, CrossRef.

Levkau B. HDL-S1P: cardiovascular functions, disease-associated alterations, and therapeutic applications. Front Pharmacol. 2015; 6: 243. doi: 10.3389/fphar.2015.00243, CrossRef.

Galvani S, Hla T. Quality versus quantity. Arterioscler Thromb Vasc Biol. 2017; 37: 1018-9, CrossRef.

Esteller A. Physiology of bile secretion. World J Gastroenterol. 2008; 14: 5641-9, CrossRef.

Paulusma CC, Folmer DE, Ho-Mok KS, de Waart DR, Hilarius PM, Verhoeven AJ, Oude Elferink RP. ATP8B1 requires an accessory protein for endoplasmic reticulum exit and plasma membrane lipid flippase activity. Hepatology. 2008; 47: 268-78, CrossRef.

Paulusma CC, Groen A, Kunne C, Ho-Mok KS, Spijkerboer AL, Rudi de Waart D, et al. Atp8b1 deficiency in mice reduces resistance of the canalicular membrane to hydrophobic bile salts and impairs bile salt transport. Hepatology. 2006; 44: 195-204, CrossRef.

Rottiers V, Näär AM. MicroRNAs in metabolism and metabolic disorders. Nat Rev Mol Cell Biol. 2012; 13: 239-50, CrossRef.

Michell DL, Vickers KC. Lipoprotein carriers of micrornas. Biochim Biophys Acta. 2016; 1861(12 Pt B): 2069-74, CrossRef.

Canfran-Duque A, Lin CS, Goedeke L, Suarez Y, Fernandez-Hernando C. Micro-RNAs and high-density lipoprotein metabolism. Arterioscler Thromb Vasc Biol. 2016; 36: 1076-84, CrossRef.

Martinez LO, Jacquet S, Esteve J-P, Rolland C, Cabezón E, Champagne E, et al. Ectopic beta-chain of ATP synthase is an apolipoprotein A-I receptor in hepatic HDL endocytosis. Nature. 2003; 421: 75-9, CrossRef.

Jacquet S, Malaval C, Martinez LO, Sak K, Rolland C, Perez C, et al. The nucleotide receptor P2Y13 is a key regulator of hepatic high-density lipoprotein (HDL) endocytosis. Cell Mol Life Sci. 2005; 62: 2508-15, CrossRef.

Goffinet M, Tardy C, Boubekeur N, Cholez G, Bluteau A, Oniciu DC, et al. P2Y13 receptor regulates HDL metabolism and atherosclerosis in vivo. PLoS One. 2014; 9: e95807. doi: 10.1371/journal.pone.0095807, CrossRef.

Fabre AC, Malaval C, Ben Addi A, Verdier C, Pons V, Serhan N, et al. P2Y13 receptor is critical for reverse cholesterol transport. Hepatology. 2010; 52: 1477-83, CrossRef.

Serhan N, Cabou C, Verdier C, Lichtenstein L, Malet N, Perret B, et al. Chronic pharmacological activation of P2Y13 receptor in mice decreases HDL-cholesterol level by increasing hepatic HDL uptake and bile acid secretion. Biochim Biophys Acta. 2013; 1831: 719-25, CrossRef.

Lichtenstein L, Serhan N, Annema W, Combes G, Robaye B, Boeynaems JM, et al. Lack of P2Y13 in mice fed a high cholesterol diet results in decreased hepatic cholesterol content, biliary lipid secretion and reverse cholesterol transport. Nutr Metab. 2013; 10: 67. doi: 10.1186/1743-7075-10-67, CrossRef.

Arakaki N, Kita T, Shibata H, Higuti T. Cell-surface Hþ-ATP synthase as a potential molecular target for anti-obesity drugs. FEBS Lett. 2007; 581: 3405-9, CrossRef.

Howard AD, Verghese PB, Arrese EL, Soulages JL. The beta-subunit of ATP synthase is involved in cellular uptake and resecretion of apoA-I but does not control apoA-I-induced lipid efflux in adipocytes. Mol Cell Biochem. 2011; 348: 155-64, CrossRef.

Lee H, Jun DJ, Suh BC, Choi BH, Lee JH, Do MS, et al. Dual roles of P2 purinergic receptors in insulin-stimulated leptin production and lipolysis in differentiated rat white adipocytes. J Biol Chem. 2005; 280: 28556-63, CrossRef.

Radojkovic C, Genoux A, Pons V, Combes G, de Jonge H, Champagne E, et al. Stimulation of cell surface F1-ATPase activity by apolipoprotein A-I inhibits endothelial cell apoptosis and promotes proliferation. Arterioscler Thromb Vasc Biol. 2009; 29: 1125-30, CrossRef.

Cavelier C, Ohnsorg PM, Rohrer L, von Eckardstein A. The beta-chain of cell surface F0F1 ATPase modulates ApoA-I and HDL transcytosis through aortic endothelial cells. Arterioscler Thromb Vasc Biol. 2012; 32: 131-9, CrossRef.

Tran-Dinh A, Diallo D, Delbosc S, Varela-Perez LM, Dang Q, Lapergue B, et al. HDL and endothelial protection. Br J Pharmacol. 2013; 169: 493-511, CrossRef.

Mineo C, Deguchi H, Griffin JH, Shaul PW. Endothelial and antithrombotic actions of HDL. Circ Res. 2006; 98: 1352-64, CrossRef.

Erlinge D, Burnstock G. P2 receptors in cardiovascular regulation and disease, Purinergic Signal. 2008; 4: 85-7, CrossRef.

Martinez LO, Najib S, Perret B, Cabou C, Lichtensein L. Ecto-F1-ATPase/P2Y pathways in metabolic and vascular functions of high density lipoproteins. Atherosclerosis. 2015; 238: 89-100, CrossRef.

Edmondson AC, Braund PS, Stylianou IM, Khera AV, Nelson CP, Wolfe ML, et al. Dense genotyping of candidate gene loci identifies variants associated with high-density lipoprotein cholesterol. Circ Cardiovasc Genet. 2011; 4: 145-55, CrossRef.

Van Capelleveen JC, Bochem AE, Motazacker MM, Hovingh GK, Kastelein JJP. Genetics of HDL-C: a causal link to atherosclerosis? Curr Atheroscler Rep. 2013; 15: 326. doi: 10.1007/s11883-013-0326-8, CrossRef.

Tuteja S, Rader DJ. High-density lipoproteins in the prevention of cardiovascular disease: changing the paradigm. Nature. 2014; 96: 48-56, CrossRef.

Goodman AL, Gordon JI. Our unindicted coconspirators: human metabolism from a microbial perspective. Cell Metab. 2010; 12:111-6, CrossRef.

Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, DuGar B, et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature. 2011; 472: 57-63, CrossRef.

Tang WH, Wang Z, Levison BS, Koeth RA, Britt EB, Fu X, et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med. 2013; 368: 1575-84, CrossRef.

Koeth RA, Wang Z, Levison BS, Buffa JA, Org E, Sheehy BT, et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med. 2013; 19: 576-85, CrossRef.

Nakaya K, Takiguchi S, Ikewaki K. A new frontier for reverse cholesterol transport. The impact of intestinal microbiota on reverse cholesterol transport. Arterioscler Thromb Vasc Biol. 2017; 37: 385-6, CrossRef.

Mineo C, Shaul PW. Regulation of signal transduction by HDL. J Lipid Res. 2013; 54: 2315-24, CrossRef.

Nofer JR. Signal transduction by HDL: agonists, receptors, and signaling cascades. Exp Pharmacol. 2015; 224: 229-56, CrossRef.

Duffy D, Rader DJ. Emerging therapies targeting high-density lipoprotein metabolism and reverse cholesterol transport. Circulation. 2006; 113: 1140-50, CrossRef.

Barter PJ, Nicholls S, Rye KA, Anantharamaiah GM, Navab M, Fogelman AM. Antiinflammatory properties of HDL. Circ Res. 2004; 95: 764-72, CrossRef.

Cockerill GW, Rye K-A, Gamble JR, Vadas MA, Barter PJ. High-density lipoproteins inhibit cytokine-induced expression of endothelial cell adhesion molecules. Arterioscler Thromb Vasc Biol. 1995; 15: 1987-94, CrossRef.

Bisoendial RJ, Hovingh GK, Levels JH, Lerch PG, Andresen I, Hayden MR, et al. Restoration of endothelial function by increasing high-density lipoprotein in subjects with isolated low high-density lipoprotein. Circulation. 2003; 107: 2944-8, CrossRef.

Seetharam D, Mineo C, Gormley AK, Gibson LL, Vongpatanasin W, Chambliss KL, et al. High-density lipoprotein promotes endothelial cell migration and reendothelialization via scavenger receptor-B type I. Circ Res. 2006; 98: 63-72, CrossRef.

Tso C, Martinic G, Fan WH, Rogers C, Rye KA, Barter PJ. High-density lipoproteins enhance progenitor-mediated endothelium repair in mice. Arterioscler Thromb Vasc Biol. 2006; 26: 1144-9, CrossRef.

Sumi M, Sata M, Miura SI, Rye KA, Toya N, Kanaoka Y, et al. Reconstituted high-density lipoprotein stimulates differentiation of endothelial progenitor cells and enhances ischemia-induced angiogenesis. Arterioscler Thromb Vasc Biol. 2007; 27: 813-18, CrossRef.

Yvan-Charvet L, Pagler T, Gautier EL, Avagyan S, Siry RL, Han S, et al. ATP-binding cassette transporters and HDL suppress hematopoietic stem cell proliferation. Science. 2010; 328: 1689-93, CrossRef.

Drew BG, Duffy SJ, Formosa MF, Natoli AK, Henstridge DC, Penfold SA, et al. High-density lipoprotein modulates glucose metabolism in patients with type 2 diabetes mellitus. Circulation. 2009; 119: 2103-11, CrossRef.

Soran H, Schofield JD, Liu Y, Durrington PN. How HDL protects LDL against atherogenic modification: paraoxonase 1 and other dramatis personae. Curr Opin Lipidol. 2015; 26: 247-56, CrossRef.

Kruger AL, Peterson S, Turkseven S, Kaminski PM, Zhang FF, Quan S, et al. D-4F induces heme oxygenase-1 and extracellular superoxide dismutase, decreases endothelial cell sloughing, and improves vascular reactivity in rat model of diabetes. Circulation. 2005; 111: 3126-34, CrossRef.

Bussolati B, Ahmed A, Pemberton H, Landis RC, Di Carlo F, Haskard DO, et al. Bifunctional role for VEGF-induced heme oxygenase-1 in vivo: induction of angiogenesis and inhibition of leukocytic infiltration. Blood. 2004; 103: 761-6, CrossRef.

Tan JTM, Ng MKC, Bursill CA. The role of high-density lipoproteins in the regulation of angiogenesis. Cardiovasc Res. 2015; 106: 184-93, CrossRef.

Van der Stoep M, Korporaal JA, van Eck M. High-density lipoprotein as a modulator of platelet and coagulation responses. Cardiovasc Res. 2014; 103: 362-71, CrossRef.

Siebel Al, Heywood SE, Kingwell BA. HDL and glucose metabolism: current evidence and therapeutic potential. Front Pharmacol. 2015; 6: 258. doi: 10.3389/fphar.2015.00258, CrossRef.

Rye KA, Barter PJ, Cochran BJ. Apolipoprotein A-1 interactions with insulin secretion and production. Curr Opin Lipidol. 2016; 27: 8-13, CrossRef.

Lim S, Park YM, Sakuma I, Koh KK. How to control residual cardiovascular risk despite statin treatment: focusing on HDL-cholesterol. Int J Cardiol 2013; 166: 8-14, CrossRef.

Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014; 129: S1-45, CrossRef.

Hafiane A, Genest J. High density lipoproteins: measurement techniques and potential biomarkers of cardiovascular risk. BBA Clin. 2015; 3: 175-88, CrossRef.

Karathanasis SK, Freeman LA, Gordon SM, Remaley AT. The changing face of HDL and the best way to measure it. Clin Chem. 2017; 63: 196-210, CrossRef.

Asztalos BF, Tani M, Schaefer EJ. Metabolic and functional relevance of HDL subspecies. Curr Opin Lipidol. 2011; 22: 176-85, CrossRef.

Tall AR. Cholesterol efflux pathways and other poten- tial mechanisms involved in the athero-protective effect of high density lipoproteins. J Intern Med. 2008; 263: 256 –73, CrossRef.

de la Llera-Moya M, Drazul-Schrader D, Asztalos BF, Cuchel M, Rader DJ, Rothblat GH. The ability to promote efflux via ABCA1 determines the capacity of serum specimens with similar high-density lipoprotein choles- terol to remove cholesterol from macrophages. Arterioscler Thromb Vasc Biol. 2010; 30: 796-801, CrossRef.

Monette JS, Hutchins PM, Ronsein GE, Wimberger J, Irwin AD, Tang C, et al. Patients with coronary endothelial dysfunction have impaired cholesterol efflux capacity and reduced HDL particle concentration. Circ Res. 2016; 119: 83-90, CrossRef.

Kontush A, Lindahl M, Lhomme M, Calabresi L, Chapman MJ, Davidson WS. Structure of HDL: particle subclasses and molecular components. In: von Eckardstein A, Kardassis D, editors. Handbook of Experimental Pharmacology. Now York: Springer; 2015. p.3-51, CrossRef.

Rosales C, Davidson WS, Gillard BK, Gotto AM Jr, Pownall HJ. Speciated high-density lipoprotein biogenesis and functionality. Curr Atheroscler Rep. 2016; 18: 25. doi: 10.1007/s11883-016-0572-7, CrossRef.

Ballantyne CM, Miller M, Niesor EJ, Burgess T, Kallend D, Stein EA. Effect of dalcetrapib plus pravastatin on lipoprotein metabolism and high-density lipoprotein composition and function in dyslipidemic patients: results of a phase IIb dose-ranging study. Am Heart J. 2012; 163: 515-21.e3, CrossRef.

Krauss RM, Wojnooski K, Orr J, Geaney JC, Pinto CA, Liu Y, et al. Changes in lipoprotein subfraction concentration and composition in healthy individuals treated with the CETP inhibitor anacetrapib. J Lipid Res. 2012; 53: 540-7, CrossRef.

Kuller LH, Grandits G, Cohen JD, Neaton JD, Prineas R. Lipoprotein particles, insulin, adiponectin, C-reactive protein and risk of coronary heart disease among men with metabolic syndrome. Atherosclerosis. 2007;195: 122–128, CrossRef.

Mackey RH, Greenland P, Goff DC Jr, Lloyd-Jones D, Sibley CT, Mora S. High-density lipoprotein cholesterol and particle concentrations, carotid atherosclerosis, and coronary events: MESA (Multi-Ethnic Study of Atherosclerosis). J Am Coll Cardiol. 2012; 60: 508-16, CrossRef.

Parish S, Offer A, Clarke R, Hopewell JC, Hill MR, Otvos JD, et al. Lipids and lipoproteins and risk of different vascular events in the MRC/BHF Heart Protection Study. Circulation. 2012; 125: 2469-78, CrossRef.

Mora S, Glynn RJ, Ridker PM. HDL cholesterol, size, particle number, and residual vascular risk after potent statin therapy. Circulation. 2013; 128: 1189-97, CrossRef.

Navab M, Hama SY, Anantharamaiah GM, Hassan K, Hough GP, Watson AD, et al. Normal high density lipoprotein inhibits three steps in the formation of mildly oxidized low density lipoprotein: steps 2 and 3. J Lipid Res. 2000; 41: 1495-508, PMID.

van Leuven SI, Hezemans R, Levels JH, Snoek S, Stokkers PC, Hovingh GK, et al. Enhanced atherogenesis and altered high density lipoprotein in patients with Crohn’s disease. J Lipid Res. 2007; 48: 2640-6, CrossRef.

Bloedon LT, Dunbar R, Duffy D, Pinell-Salles P, Norris R, DeGroot BJ, et al. Safety, pharmacokinetics, and pharmacodynamics of oral apoA-I mimetic peptide D-4F in high-risk cardiovascular patients. J Lipid Res. 2008; 49: 1344-352, CrossRef.

Gebhard C, Rhainds D, Tardif JC. HDL and cardiovascular risk: is cholesterol in particle subclasses relevant? Eur Heart J 2015; 36: 10-2, CrossRef.

Sattler KJE, Elbasan Ş, Keul P, Elter-Schulz M, Bode C, Gräler MH, et al. Sphingosine 1-phosphate levels in plasma and HDL are altered in coronary artery disease. Basic Res Cardiol. 2010; 105: 821-32, CrossRef.

Argraves KM, Sethi AA, Gazzolo PJ, Wilkerson BA, Remaley AT, Tybjaerg-Hansen A, et al. S1P, dihydro-S1P and C24:1-ceramide levels in the HDL-containing fraction of serum inversely correlate with occurrence of ischemic heart disease. Lipids Health Dis. 2011; 10: 70. doi: 10.1186/1476-511x-10-70, CrossRef.

Xiong X, Liu H, Hua L, Zhao H, Wang D, Li Y. The association of HDL-apoCIII with coronary heart disease and the effect of statin treatment on it. Lipids Health Dis. 2015; 14: 127. doi: 10.1186/s12944-015-0129-8, CrossRef.

Chang PY, Lee CM, Hsu HC, Lin HJ, Chien KL, Chen MF, et al. Identification of the HDL-ApoCIII to VLDL-ApoCIII ratio as a predictor of coronary artery disease in the general population: the Chin-Shan Community Cardiovascular Cohort (CCCC) study in Taiwan. Lipids Health Dis. 2012; 11: 162. doi: 10.1186/1476-511x-11-162, CrossRef.

Besler C, Heinrich K, Rohrer L, Doerries C, Riwanto M, Shih DM, et al. Mechanisms underlying adverse effects of HDL on eNOS-activating pathways in patients with coronary artery disease. J Clin Invest. 2011; 121: 2693-708, CrossRef.

Kasumov T, Willard B, Li L, Li M, Conger H, Buffa JA, et al. 2H2O-based high-density lipoprotein turnover method for the assessment of dynamic high-density lipoprotein function in mice. Arterioscler Thromb Vasc Biol. 2013; 33: 1994-2003, CrossRef.

Martinez LO, Genoux A, Ferrieres J, Duparc T, Perret B. Serum inhibitory factor 1, high-density lipoprotein and cardiovascular diseases. Curr Opin Lipidol 2017; 28: 337-46, CrossRef.

Genoux A, Lichtenstein L, Ferrières J, Duparc T, Bongard V, Vervueren PL, et al. Serum levels of mitochondrial inhibitory factor 1 are independently associated with long-term prognosis in coronary artery disease: the GENES Study. BMC Med. 2016; 14: 125. doi: 10.1186/s12916-016-0672-9, CrossRef.

Sharrett AR, Ballantyne CM, Coady SA, Heiss G, Sorlie PD, Catellier D, et al. Coronary heart disease prediction from lipoprotein cholesterol levels, triglycerides, lipoprotein(a), apolipoproteins A-I and B, and HDL density subfractions: the atherosclerosis risk in communities (aric) study. Circulation. 2001; 104: 1108-13, CrossRef.

Gordon T, Castelli WP, Hjortland MC, Kannel WB, Dawber TR. High density lipoprotein as a protective factor against coronary heart disease. The Framingham Study. Am J Med. 1977; 62: 707-14, CrossRef.

Gordon DJ, Probst eld JL, Garrison RJ, Neaton JD, Castelli WP, Knoke JD, et al. High-density lipoprotein cholesterol and cardiovascular disease. Four prospective American studies. Circulation. 1989; 79: 8-15, CrossRef.

Di Angelantonio E, Sarwar N, Perry P, Kaptoge S, Ray KK, Thompson A, et al. Major lipids, apolipoproteins, and risk of vascular disease. JAMA. 2009; 302: 1993-2000, CrossRef.

Barter P, Gotto AM, LaRosa JC, Maroni J, Szarek M, Grundy SM, et al. HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events. N Engl J Med. 2007; 357: 1301-10, CrossRef.

Ginsberg HN, Elam MB, Lovato LC, Crouse JR 3rd, Leiter LA, Linz P, et al. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med. 2010; 362: 1563-74, CrossRef.

von Eckardstein A. Implications of torcetrapib failure for the future of HDL therapy: is HDL-cholesterol the right target? Expert Rev Cardiovasc Ther. 2010; 8: 345-58, CrossRef.

Besler C, Lüscher TF, Landmesser U. Molecular mechanisms of vascular effects of High-density lipoprotein: alterations in cardiovascular disease. EMBO Mol Med. 2012; 4: 251-68, CrossRef.

Luscher TF, Landmesser U, von Eckardstein A, Fogelman AM. High-density lipoprotein. Vascular protctive effcts, dysfunction, and potential as therapeutic target. Circ Res. 2014; 114: 171- 82, CrossRef.

Verges B, Florentin E, Baillot-Rudoni S, Petit JM, Brindisi MC, Pais de Barros JP, et al. Rosuvastatin 20 mg restores normal HDL-apoA-I kinetics in type 2 diabetes. J Lipid Res. 2009; 50: 1209-15, CrossRef.

Verdier C, Martinez LO, Ferrieres J, Elbaz M, Genoux A, Perret B. Targeting high-density lipoproteins: update on a promising therapy. Arch of Cardiol Dis. 2013; 106: 601-11, CrossRef.

Mineo C, Shaul PW. PON-dering differences in HDL function in coro- nary artery disease. J Clin Invest. 2011; 121: 2545-8, CrossRef.

Calkin AC, Drew BG, Ono A, Duffy SJ, Gordon MV, Schoenwaelder SM, et al. Reconstituted high-density lipoprotein attenuates platelet function in individuals with type 2 diabetes mellitus by promoting cholesterol efflux. Circulation. 2009; 120: 2095-104, CrossRef.

Murphy AJ, Bijl N, Yvan-Charvet L, Welch CB, Bhagwat N, Reheman A, et al. Cholesterol efflux in megakaryocyte progenitors suppresses platelet production and thrombocytosis. Nature Med. 2013; 19: 586-594, CrossRef.

Kontush A, Therond P, Zerrad A, Couturier M, Negre-Salvayre A, de Souza JA, et al. Preferential sphingosine-1-phosphate enrichment and sphingomyelin depletion are key features of small dense HDL3 particles: relevance to antiapoptotic and antioxidative activities. Arterioscler Thromb Vasc Biol. 2007; 27: 1843-9, CrossRef.

Patel S, Drew BG, Nakhla S, Duffy SJ, Murphy AJ, Barter PJ, et al. Reconstituted high-density lipoprotein increases plasma high-density lipoprotein anti-inflammatory properties and cholesterol efflux capacity in patients with type 2 diabetes. J Am Coll Cardiol. 2009; 53: 962-71, CrossRef.

De Souza JA, Vindis C, Nègre-Salvayre A, Rye K-A, Couturier M, Therond P, et al. Small, dense HDL 3 particles attenuate apoptosis in endothelial cells: pivotal role of apolipoprotein A-I. J Cell Mol Med. 2010; 14: 608-20, CrossRef.

Nieuwdorp M, Vergeer M, Bisoendial RJ, op ‘t Roodt J, Levels H, Birjmohun RS, et al. Reconstituted HDL infusion restores endothelial function in patients with type 2 diabetes mellitus. Diabetologia. 2008; 51: 1081-4, CrossRef.

Spieker LE, Sudano I, Hürlimann D, Lerch PG, Lang MG, Binggeli C, et al. High-density lipoprotein restores endothelial function in hypercholesterolemic men. Circulation. 2002; 105: 1399-402, PMID.

Besler C, Heinrich K, Rohrer L, Doerries C, Riwanto M, Shih DM, et al. Mechanisms underlying adverse effects of HDL on eNOS-activating pathways in patients with coronary artery disease. J Clin Invest. 2011; 121: 2693-708, CrossRef.

Barter PJ, Rye KA, Tardif JC, Waters DD, Boekholdt SM, Breazna A, et al. Effect of torcetrapib on glucose, insulin, and hemoglobin A1c in subjects in the Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events (ILLUMINATE) trial. Circulation. 2011; 124: 555-62, CrossRef.

Drew BG, Duffy SJ, Formosa MF, Natoli AK, Henstridge DC, Penfold SA, et al. High-density lipoprotein modulates glucose metabolism in patients with type 2 diabetes mellitus. Circulation. 2009; 119: 2103-11, CrossRef.

Fryirs MA, Barter PJ, Appavoo M, Tuch BE, Tabet F, Heather AK, et al. Effects of high-density lipoproteins on pancreatic β-cell insulin secretion. Arterioscler Thromb Vasc Biol. 2010; 30: 1642-8, CrossRef.

Kingwell BA, Chapman MJ, Kontush A, Miller NE. HDL-targeted therapies progress, failure and future. Nat Rev Drug Discov. 2014; 13: 445-64, CrossRef.

Hernaez A, Farraz M, Fito M. Olive oil phenolic compounds and high-density lipoprotein function. Curr Opin Lipidol. 2016; 27: 47-53, CrossRef.

Annema W, von Eckardstein A. high-density lipoprotein-multifunctional but vulnerable protection from atherosclerosis. Circ J. 2013; 77: 2432-48, CrossRef.




DOI: https://doi.org/10.18585/inabj.v10i2.465

Indexed by:

                 

                

                

  

 

The Prodia Education and Research Institute