ЛИПОПРОТЕИНЫ ВЫСОКОЙ ПЛОТНОСТИ: ОТ КОЛИЧЕСТВЕННЫХ ПОКАЗАТЕЛЕЙ К ФУНКЦИОНАЛЬНОЙ ОЦЕНКЕ И ТЕРАПИИ (ОБЗОР ЛИТЕРАТУРЫ)

Антиатерогенная роль липопротеинов высокой плотности (ЛПВП) связана, прежде всего, с их участием в обратном транспорте избытка холестерина из периферических тканей в печень. Эффективность данного механизма зависит от способности аполипопротеина А-I (апоА-I) - основного белкового компонента ЛПВП, захватывать холестерин из клеток. Как известно, акцепторные свойства данного белка могут изменяться под влиянием различных факторов. В обзоре обсуждаются современные подходы, направленные как на повышение уровня ЛПВП в плазме крови, так и на сохранение их нативных функциональных свойств. В качестве одного из ключевых критериев функциональности ЛПВП предлагается определять способность ЛПВП осуществлять отток холестерина из макрофагов. Исследования показали, что введение в организм реконструированных ЛПВП или пептидов-миметиков апоА-I ускоряет отток холестерина из периферических тканей, улучшает состояние эндотелия сосудов и приводит к регрессии атеросклеротической бляшки. Таким образом, терапия с использованием реконструированных ЛПВП и/или апоА-I-миметиков может стать эффективным способом лечения сердечно-сосудистых заболеваний, вызванных накоплением холестерина в сосудистой стенке. Поиск литературы проведён по базам данных: Scopus, Web of Science, MedLine, Pubmed, Consilium medicum, CyberLeninka, Pubfacts, MedBookAide, Mediasphera.ru, SpringerLink, BioMedSearch.com., ResearchGate.net., Google Scholar, РИНЦ.

Kajani S., Curley S., McGillicuddy F.C. Unravelling HDL-Looking beyond the cholesterol surface to the quality within.Int. J. Mol. Sci. 2018; 19(7): E1971. https://doi.org/10.3390/ijms19071971

Jomard A., Osto E. High density lipoprotein: metabolism, function, and therapeutic potential. Front. Cardiovasc. Med. 2020; 7(39): 1-12. https://doi.org/10.3389/fcvm.2020.00039

Barter P.J., Rye K.A. Targeting High-density Lipoproteins to Reduce Cardiovascular Risk: What Is the Evidence? Clin Ther. 2015; 37(12): 2716-2731. https://doi.org/10.1016/j.clinthera.2015.07.021

Brites F., Martin M., Guillas I., Kontush A. Antioxidative activity of high-density lipoprotein (HDL): mechanistic insights into potential clinical benefit. BBA Clin. 2017; 8: 66-77. https://doi.org/10.1016/j.bbacli.2017.07.002

Soran H., Schofield J.D., Durrington P.N. Antioxidant properties of HDL. Front. Pharmacol. 2015; 6: 222. https://doi.org/10.3389/fphar.2015.00222

Hou L., Tang S., Wu B.J., Ong K.L., Westerterp M., Barter P.J. et al. Apolipoprotein A-I improves pancreatic β-cell function independent of the ATP-binding cassette transporters ABCA1 and ABCG1. FASEB J. 2019; 33(7): 8479-89. https://doi.org/10.1096/fj.201802512RR

Потеряева О.Н., Усынин И.Ф. Антидиабетическая роль липопротеинов высокой плотности. Биомедицинская химия. 2018; 64(6): 463-71. https://doi.org/10.18097/ PBMC20186406463

Sirtori C.R., Ruscica M., Calabresi L., Chiesa G., Giovannoni R., Badimon J.J. HDL therapy today: from atherosclerosis, to stent compatibility to heart failure. Ann. Med. 2019; 51(7-8): 345-59. https://doi.org/10.1080/07853890.2019.1694695 Review.

Karalis I., Jukema J.W. HDL mimetics infusion and regression of atherosclerosis: is it still considered a valid therapeutic option? Curr. Cardiol. Rep. 2018; 20(8): 66. https://doi.org/10.1007/s11886-018-1004-9

Перова Н.В. Атеромаркеры липопротеинов высокой плотности. Ч. II. Липопротеины высокой плотности: структура, состав, физико-химические и физиологические антиатерогенные свойства, их механизмы и маркеры (обзор литературы). Профилактическая медицина. 2017; 20(4): 37-44. https://doi.org/10.17116/profmed201720437-44

Торховская Т.И., Кудинов В.А., Захарова Т.С., Маркин С.С. Дисфункциональные липопротеины высокой плотности: роль в атерогенезе и потенциальные мишени для фосфолипидной терапии. Кардиология. 2018; 58(3): 73-83. https://doi.org/10.18087/cardio.2018.3.10101

Ossoli A., Simonelli S., Varrenti M., Morici N., Oliva F., Stucchi M. et al. Recombinant LCAT (Lecithin:Cholesterol Acyltransferase) rescues defective HDL (High-Density Lipoprotein)-mediated endothelial protection in acute coronary syndrome. Arterioscler. Thromb. Vasc. Biol. 2019; 39(5): 915-24. https://doi.org/10.1161/ATVBAHA.118.311987

Rosenson R.S., Brewer H.B., Ansell B.J., Barter P., Chapman M.J., Heinecke J.W. et al. Dysfunctional HDL and atherosclerotic cardiovascular disease. Nat. Rev. Cardiol. 2016; 13(1): 48-60. https://doi.org/10.1038/nrcardio.2015.124

Hwang Y.-C., Ahn H-Y., Park S.-W., Park C.-Y. Association of HDL-C and apolipoprotein A-I with the risk of type 2 diabetes in subjects with impaired fasting glucose. Eur. J. Endocrin. 2014; 171: 137-42. https://doi.org/10.1530/EJE-14-0195

Madsen C.M., Varbo A., Nordestgaard B.G. Extreme high high-density lipoprotein cholesterol is paradoxically associated with high mortality in men and women: two prospective cohort studies. Eur. Heart J. 2017; 38(32): 2478-86. https://doi.org/10.1093/eurheartj/ehx163

Gille A., D’Andrea D., Tortorici M.A., Hartel G., Wright S.D. CSL112 (apolipoprotein A-I [human]) enhances cholesterol efflux similarly in healthy individuals and stable atherosclerotic disease patients highlights. Arterioscler. Thromb.Vasc. Biol. 2018; 38(4): 953-63. https://doi.org/10.1161/atvbaha.118.310538

Allard-Ratick M.P., Kindya B.R., Khambhati J., Engels M.C., Sandesara P.B., Rosenson R.S. et al. HDL: fact, fiction, or function? HDL cholesterol and cardiovascular risk. Eur. J. Prev. Cardiolog. 2019; 123(10): 1736-7. https://doi.org/10.1177/2047487319848214

Marques L.R., Diniz T.A., Antunes B.M., Rossi F.E., Caperuto E.C., Lira F.S. et al. Reverse cholesterol transport: molecular mechanisms and the non-medical approach to enhance HDL cholesterol. Front Physiol. 2018; 9: 526. https://doi.org/10.3389/fphys.2018.00526

Kosmas C.E., Martinez I., Sourlas A., Kyriaki V., Bouza K.V., Campos F.N. et al. High-density lipoprotein (HDL) functionality and its relevance to atherosclerotic cardiovascular disease. Drugs in Context. 2018; 7: 212525. https://doi.org/10.7573/dic.212525

Метельская В.А. Функциональная многогранность липопротеинов высокой плотности: поиск золотой середины. Атеросклероз. 2021; 17(2): 61-71. https://doi.org/10.52727/2078-256X-2021-17-2-61-71

Потеряева О.Н., Усынин И.Ф. Терапевтические подходы к восстановлению антиатерогенной функции липопротеинов высокой плотности. Якутский медицинский журнал. 2021; 75(3): 98-103. https://doi.org/10.25789/YMJ.2021.75.25

Ferri N., Corsini A., Sirtori C.R., Ruscica M. Present therapeutic role of cholesteryl ester transfer protein inhibitors. Pharmacol. Res. 2018; 128: 29-41. https://doi.org/10.1016/j.phrs.2017.12.028

Tall A.R., Rader D.J. Trials and tribulations of CETP inhibitors. Circ. Res. 2018; 122(1): 106-12. https://doi.org/10.1161/CIRCRESAHA.117.311978

Barter P., Genest J. HDL cholesterol and ASCVD risk stratification: A debate. Atherosclerosis. 2019; 283: 7-12. https://doi.org/10.1016/j.atherosclerosis.2019.01.001

Barter P.J., Caulfield M., Eriksson M., Grundy S.M., Kastelein J.JP., Komajda M. et al. Effects of torcetrapib in patients at high risk for coronary events. N. Engl. J. Med. 2007; 357(21): 2109-22. https://doi.org/10.1056/NEJMoa0706628

Bagdade J., Barter P., Quiroga C., Alaupovic P. Effects of torcetrapib and statin treatment on apoC-III and apoprotein-defined lipoprotein subclasses (from the ILLUMINATE Trial). Am. J. Cardiol. 2017; 119(11): 1753-6. https://doi.org/10.1016/j.amjcard.2017.02.049

Schwartz G.G., Olsson A.G., Abt M., Ballantyne C.M., Barter P.J., Brumm J. et al. Effects of dalcetrapib in patients with a recent acute coronary syndrome. N. Engl. J. Med. 2012; 367(22): 2089-99. https://doi.org/10.1056/NEJMoa1206797

Tardif J.-C., Rhainds D., Rheaume E., Dube M.-P. CETP: Pharmacogenomics-Based Response to the CETP Inhibitor Dalcetrapib. Arterioscler. Thromb. Vasc. Biol. 2017; 37(3): 396-400. https://doi.org/10.1161/ATVBAHA.116.307122

Nicholls S.J., Ruotolo G., Brewer H.B., Kane J.P., Wang M.D., Krueger K.A. et al. Cholesterol efflux capacity and pre-beta-1 HDL concentrations are increased in dyslipidemic patients treated with evacetrapib. JACC. 2015; 66: 2201-10. https://doi.org/10.1016/j.jacc.2015.09.013

Lincoff A.M., Nicholls S.J., Riesmeyer J.S., Barter P.J., Brewer H.B, Fox K.A.A.et al. Evacetrapib and cardiovascular outcomes in high-risk vascular disease. N. Engl. J. Med. 2017; 376(20): 1933-42. https://doi.org/10.1056/NEJMoa1609581

Bloomfield D., Carlson G.L., Sapre A., Tribble D., McKenney J.M., Littlejohn T.W. et al. Efficacy and safety of the cholesteryl ester transfer protein inhibitor anacetrapib as monotherapy and coadministered with atorvastatin in dyslipidemic patients. Am. Heart J. 2009; 157(2): 352-60. https://doi.org/10.1016/j.ahj.2008.09.022

Gotto A.M., Kher Jr., U., Chatterjee M.S., Liu Y., Li X.S., Vaidya S. et al. Lipids, safety parameters, and drug concentrations after an additional 2 years of treatment with anacetrapib in the DEFINE study. J. Сardiovasc. Pharmacol. Ther. 2014; 19(6): 543-9. https://doi.org/10.1177/1074248414529621

HPS3/TIMI55-REVEAL Collaborative Group, Bowman L., Hopewell J.C., Chen F., Wallendszus K., Stevens W., Collins R. et al. Effects of anacetrapib in patients with atherosclerotic vascular disease. N. Engl. J. Med. 2017; 377(13): 1217-27. https://doi.org/10.1056/NEJMoa1706444

Di Bartolo B.A., Nicholls S.J. Anacetrapib as a potential cardioprotective strategy. Drug. Des. Devel. Ther. 2017; 11:3497-502. https://doi.org/10.2147/DDDT.S114104

Barter P.J., Cochran B.J., Rye K.A. CETP inhibition, statins and diabetes. Atherosclerosis. 2018; 278: 143-6. https://doi.org/10.1016/j.atherosclerosis.2018.09.033

Masson W., Lobo M., Siniawski D., Huerin M., Molinero G., Valero R. et al. Therapy with cholesteryl ester transfer protein (CETP) inhibitors and diabetes risk. Diabetes Metab. 2018; 44(6): 508-13. https://doi.org/10.1016/j.diabet.2018.02.005

Parolini C., Adorni M.P., Busnelli M., Manzini S., Cipollari E., Favari E. et al. Can infusions of large synthetic HDL containing trimeric apoA-I stabilize atherosclerotic plaques in hypercholesterolemic rabbits. J. Cardiol. 2019; 35(10): 1400-8. https://doi.org/10.1016/j.cjca.2019.05.033

Chen W., Wu Y., Lu Q., Wang S., Xing D. Endogenous ApoA-I expression in macrophages: a potential target for protection against atherosclerosis. Clin. Chim. Acta. 2020; 505: 55-9. https://doi.org/10.1016/j.cca.2020.02.025

Shaw J.A., Bobik A., Murphy A., Kanellakis P., Blombery P., Mukhamedova N. et al. Infusion of reconstituted high-density lipoprotein leads to acute changes in human atherosclerotic plaque. Circ. Res. 2008; 103(10): 1084-91. https://doi.org/10.1161/CIRCRESAHA.108.182063

Tardif J.C., Gregoire J., L’Allier P.L., Ibrahim R., Lesperance J., Heinonen T.M. et al. Effects of reconstituted high-density lipoprotein infusions on coronary atherosclerosis: a randomized controlled trial. JAMA. 2007; 297(15): 1675-82. https://doi.org/10.1001/jama.297.15.jpc70004

Cuadrado-Godia E., Regueiro A., Nunez J., Diaz-Ricard M., Novella S., Oliveras A. et al. Endothelial progenitor cells predict cardiovascular events after atherothrombotic stroke and acute myocardial infarction. A PROCELL Substudy. PLOS ONE. 2015; 10(9): e0132415. https://doi.org/10.1371/journal.pone.0132415

Gebhard C., Rheaume E., Berry C., Brand G., Kernaleguen A.E., Theberge-Julien G. et al. Beneficial effects of reconstituted high-density lipoprotein (rHDL) on circulating CD34+ cells in patients after an acute coronary syndrome. PLOS ONE. 2017. 12(1): e0168448. https://doi.org/10.1371/journal.pone.0168448

Gibson M.C., Korjian S., Tricoci P., Daaboul Y., Yee M., Jain P. et al. Safety and tolerability of CSL112, a reconstituted, infusible, plasma-derived apolipoprotein A-I, after acute myocardial infarction: The AEGIS-I Trial (ApoA-I Event Reducing in Ischemic Syndromes I). Circulation. 2016; 134(24): 1918-30. https://doi.org/10.1016/S0735-1097(18)30706-X

Gille A., D’Andrea D., Tortorici M.A., Hartel G., Wright S.D. CSL112 (apolipoprotein A-I [human]) enhances cholesterol efflux similarly in healthy individuals and stable atherosclerotic disease patients highlights. Arterioscler. Thromb. Vasc. Biol. 2018; 38(4): 953-63. https://doi.org/10.1161/atvbaha.118.310538

Andrews J., Janssan A., Nguyen T., Pisaniello A.D., Scherer D.J., Kastelein J.J. et al. Effect of serial infusions of reconstituted high-density lipoprotein (CER-001) on coronary atherosclerosis: rationale and design of the CARAT study. Cardiovasc. Diagn. Ther. 2017; 7(1): 45-51. https://doi.org/10.21037/cdt.2017.01.01

Tardy C., Goffinet M., Boubekeur N., Cholez G., Ackermann R., Sy G. et al. HDL and CER001 Inverse-Dose Dependent Inhibition of Atherosclerotic Plaque Formation in apoE-/- Mice: Evidence of ABCA1 Down-Regulation. PLOS ONE. 2015; 10: e0137584. https://doi.org/10.1371/journal.pone.0137584

Kootte R.S., Smits L.P., van der Valk F.M., Dasseux J-L., Keyserling C., Barbaras R. et al. Effect of open-label infusion of an apoA-I-containing particle (CER-001) on RCT and artery wall thickness in patients with FHA. J. Lipid. Res. 2015; 56(3): 703-12. https://doi.org/10.1194/jlr.M055665

Hovingh G.K., Smits L.P., Stefanutti C., Soran H., Kwok S., De Graaf J. et al. The effect of an apolipoprotein A-I-containing high-density lipoproteinmimetic particle (CER-001) on carotid artery wall thickness in patients with homozygous familial hypercholesterolemia: The Modifying Orphan Disease Evaluation (MODE) study. Am. Heart J. 2015; 169(5): 736-42.e1. https://doi.org/10.1016/j.ahj.2015.01.008

Tardif J.-C., Ballantyne C.M., Barter P., Dasseux J.-L., Fayad Z.A., Guertin M-C. et al. Effects of the high density lipoprotein mimetic agent CER-001 on coronary atherosclerosis in patients with acute coronary syndromes: a randomized trial. Eur. Heart. J. 2014; 35(46): 3277-86. https://doi.org/10.1093/eurheartj/ehu171

Nicholls S.J., Andrews J., Kastelein J.J.P., Merkely B., Nissen S.E., Ray K.K.et al. Effect of serial infusions of CER-001, a pre-β high-density lipoprotein mimetic, on coronary atherosclerosis in patients following acute coronary syndromes in the CER-001 atherosclerosis regression acute coronary syndrome trial: a randomized clinical trial. JAMA Cardiol. 2018; 3(9): 815-22. https://doi.org/10.1001/jamacardio.2018.2121

Kataoka Y., Andrews J., Duong M., Nguyen T., Schwarz N., Fendler J. et al. Regression of coronary atherosclerosis with infusions of the high-density lipoprotein mimetic CER-001 in patients with more extensive plaque burden. Cardiovasc. Diagn. Ther. 2017; 7(3): 252-63. https://doi.org/10.21037/cdt.2017.02.01

Rye K-A., Barter P.J. Cardioprotective functions of HDLs. J. Lipid Res. 2013; 55(2): 168-79. https://doi.org/10.1194/jlr.R039297

Takata K., Di Bartolo B.A., Nicholls S.J. High-density lipoprotein infusions. Cardiol Clin. 2018; 36(2): 311-5. https://doi.org/10.1016/j.ccl.2017.12.012

Nissen S.E., Tsunoda T., Tuzcu E.M., Schoenhagen P., Cooper C.J., Yasin M. et al. Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial. JAMA. 2003; 290(17): 2292-2300. https://doi.org/10.1001/jama.290.17.2292

Wang L., Tian F., Arias A., Yang M., Sharifi B.G., Shah P.K.Comparative effects of diet-induced lipid lowering versus lipid lowering along with apoA-I Milano gene therapy on regression of atherosclerosis. J. Cardiovasc. Pharmacol. Ther. 2016; 21(3): 320-8. https://doi.org/10.1177/1074248415610216

Wacker B.K., Dronadula N., Bi L., Stamatikos A., Dichek D.A. Apo A-I (Apolipoprotein A-I) vascular gene therapy provides durable protection against atherosclerosis in hyperlipidemic rabbits. Arterioscler. Thromb. Vasc. Biol. 2018; 38(1): 206-17. https://doi.org/10.1161/ATVBAHA.117.309565

Stamatikos A., Dronadula N., Ng P., Palmer D., Knight E., Wacker B.K et al. ABCA1 overexpression in endothelial cells in vitro enhances apoAI-mediated cholesterol efflux and decreases inflammation. Hum. Gene Ther. 2019; 30(2): 236-348. https://doi.org/10.1089/hum.2018.120

Dunbar R.L., Movva R., Bloedon L.T., Duffy D., Norris R.B., Navab M. et al. Oral apolipoprotein A-I mimetic D-4F lowers HDL-inflammatory index in high-risk patients: a first-in-human multiple-dose, randomized controlled trial. Clin. Transl. Sci. 2017; 10: 455-69. https://doi.org/10.1111/cts.12487

Xu W., Qian M., Huang C., Cui P., Li W., Du Q. et al.Comparison of mechanisms of endothelial cell protections between high-density lipoprotein and apolipoprotein A-I mimetic peptide. Front. Pharmacol. 2019; 10: 817. https://doi.org/10.3389/fphar.2019.00817

Liu D., Ding Z., Wu M., Xu W., Qian M., Du Q. et al. The apolipoprotein A-I mimetic peptide, D-4F, alleviates ox-LDL-induced oxidative stress and promotes endothelial repair through the eNOS/HO-1 pathway. JMCC. 2017; 105: 77-88. https://doi.org/10.1016/j.yjmcc.2017.01.017

Moreira R.S., Irigoyen M.C., Capcha J.M.C., Sanches T.R., Gutierrez P.S., Garnica M.R. et al. Synthetic apolipoprotein A-I mimetic peptide 4F protects hearts and kidneys after myocardial infarction. Am. J. Physiol. Regul.Integr.Comp. Physiol. 2020; 318(3): R529-R544. https://doi.org/10.1152/ajpregu.00185.2019

You J., Wang J., Xie L., Zhu C., Xiong, J. D-4F, an apolipoprotein A-I mimetic, inhibits TGF-β1 induced epithelial-mesenchymal transition in human alveolar epithelial cell. Exp. Toxicol. Pathol. 2016; 68(9): 533-41. https://doi.org/10.1016/j.etp.2016.07.005

Peng M., Zhang Q., Liu Y., Guo X., Ju J., Xu L. et al. Apolipoprotein A-I mimetic peptide L-4F suppresses granulocytic-myeloid-derived suppressor cells in mouse pancreatic cancer. Front. Pharmacol. 2020; 11: 576. https://doi.org/10.3389/fphar.2020.00576

Delk S.C., Chattopadhyay A., Escola-Gil J.C., Fogelman A.M., Reddy S.T. Apolipoprotein mimetics in cancer. Semin. Cancer Biol. 2021; 73: 158-68. https://doi.org/10.1016/j.semcancer.2020.11.002

Nikolic D., Rizzo M., Mikhailidis D.P., Wong N.C., Banach M. An evaluation of RVX-208 for the treatment of atherosclerosis. Expert. Opin. Investig. Drugs. 2015; 24(10): 1389-98. https://doi.org/10.1517/13543784.2015.1083010

Bailey D., Jahagirdar R., Gordon A., Hafiane A., Campbell S., Chatur S. et al. RVX-208: a small molecule that increases apolipoprotein A-I and high-density lipoprotein cholesterol in vitro and in vivo. JACC. 2010; 55: 2580-9. https://doi.org/10.1016/j.jacc.2010.02.035

Nicholls S.J., Puri R., Wolski K., Ballantyne C.M., Barter P.J., Brewer H.B. et al. Effect of the BET protein inhibitor, RVX-208, on progression of coronary atherosclerosis: results of the phase 2b, randomized, double-blind, multicenter, ASSURE trial. Am. J. Cardiovasc. Drugs. 2016; 16(1): 55-65. https://doi.org/10.1007/s40256-015-0146-z

Morton J., Bao S., Vanags L.Z., Tsatralis T., Ridiandries A., Siu C.W. et al. Strikingly different atheroprotective effects of apolipoprotein A-I in early- versus late-stage atherosclerosis. JACC Basic. Transl. Sci. 2018; 3(2): 187-99. https://doi.org/10.1016/j.jacbts.2017.11.004