Эпигенетические лекарства: новый рубеж в лечении сердечной недостаточности

Эпигенетические лекарства: новый рубеж в лечении сердечной недостаточности

Автор: Айтбаев К.А., Муркамилов И.Т., Муркамилова Ж.А., Фомин В.В., Кудайбергенова И.О., Юсупова Т.Ф., Юсупов Ф.А.

Журнал: Евразийский кардиологический журнал @eurasian-cardiology-journal

Рубрика: Обзор

Статья в выпуске: 4, 2023 года.

Бесплатный доступ

Раскрытие секретов гибкости генома не только способствовало развитию исследований в этой области, но также послужило толчком к разработке новых методов лечения болезней человека. Лучшее понимание биологии хроматина (комплексы ДНК/гистоны) и некодирующих РНК (нкРНК) позволило разработать эпигенетические (эпи) препараты, способные модулировать программы транскрипции, связанные с сердечно-сосудистыми заболеваниями. Это особенно относится к сердечной недостаточности, где было показано, что эпигенетические механизмы лежат в основе развития некоторых патологических процессов, таких как гипертрофия левого желудочка, фиброз, апоптоз кардиомиоцитов и дисфункция микрососудов. Ориентация на эпигенетические сигналы может представлять собой многообещающий подход, особенно у пациентов с сердечной недостаточностью с сохраненной фракцией выброса (СНсФВ), где прогноз остается неблагоприятным, а эффективных методов лечения пока не существует. В этих условиях эпигенетика может использоваться для разработки индивидуальных терапевтических подходов, что прокладывает путь к персонализированной медицине. Несмотря на то, что благоприятные эффекты эпи-препаратов привлекают всё большее внимание, количество эпигенетических соединений, используемых в клинической практике, остается низким, что свидетельствует о необходимости разработки более селективных эпи-препаратов. В настоящем обзоре мы приводим перечень новых перспективных эпи-препаратов для лечения сердечно-сосудистых заболеваний, с акцентом, главным образом, на СНсФВ. Терапевтический эффект этих препаратов обусловлен воздействием как минимум на один из трёх основных эпигенетических механизмов: метилирование ДНК, модификация гистонов и некодирующие РНК.

Еще

Сердечная недостаточность, эпи-терапия, персонализированная медицина

Короткий адрес: https://sciup.org/143181072

IDR: 143181072   |   DOI: 10.38109/2225-1685-2023-4-76-82

Список литературы Эпигенетические лекарства: новый рубеж в лечении сердечной недостаточности

  • Weinhold B. Epigenetics: the science of change. Environ Health Perspect. 2006;114:A160–7. https://doi.org/10.1289/ehp.114-a160
  • Rozek LS, Dolinoy DC, Sartor MA, Omenn GS. Epigenetics: relevance and implications for public health. Annu Rev Public Health. 2014;35:105– 22. https://doi.org/10.1146/annurev-publhealth-032013-182513
  • Maunakea AK, Nagarajan RP, Bilenky M et al. Conserved role of intragenic DNA methylation in regulating alternative promoters. Nature. 2010;466:253–7. https://doi.org/10.1038/nature09165
  • Mohammed SA, Ambrosini S, Lüscher T et al. Epigenetic control of mitochondrial function in the vasculature. Front Cardiovasc Med. 2020;7:28. https://doi.org/10.3389/fcvm.2020.00028
  • Handy DE, Castro R, Loscalzo J. Epigenetic modifications: basic mechanisms and role in cardiovascular disease. Circulation. 2011;123:2145–56. https://doi.org/10.1161/CIRCULATIONAHA.110.956839
  • Gao J, Shao K, Chen X et al. The involvement of post-translational modifications in cardiovascular pathologies: focus on SUMOylation, neddylation, succinylation, and prenylation. J Mol Cell Cardiol. 2020;138:49–58. https://doi.org/10.1016/j.yjmcc.2019.11.146
  • Das S, Shah R, Dimmeler S et al. Noncoding RNAs in cardiovascular disease: current knowledge, tools and technologies for investigation, and future directions: a scientific statement from the American heart association. Circ Genom Precis Med. 2020;13:e000062. https://doi.org/10.1161/HCG.0000000000000062
  • Zhong J, Agha G, Baccarelli AA. The role of DNA methylation in cardiovascular risk and disease. Circ Res. 2016;118:119–31. https://doi.org/10.1161/CIRCRESAHA.115.305206
  • Aggarwal R, Jha M, Shrivastava A, Jha AK. Natural compounds: role in reversal of epigenetic changes. Biochemistry. 2015;80:972–89. https://doi.org/10.1134/S0006297915080027
  • Ganesan A, Arimondo PB, Rots MG et al. The timeline of epigenetic drug discovery: from reality to dreams. Clin Epigenet. 2019;11:174. https://doi.org/10.1186/s13148-019-0776-0
  • Savarese G, Becher PM, Lund LH et al. Global burden of heart failure: a comprehensive and updated review of epidemiology. Cardiovasc Res. 2023 Jan 18;118(17):3272-3287. https://doi.org/10.1093/cvr/cvac013
  • Redfield MM, Borlaug BA. Heart Failure With Preserved Ejection Fraction: A Review. JAMA. 2023 Mar 14;329(10):827-838. https://doi.org/10.1001/jama.2023.2020
  • Skinner MK. Role of epigenetics in developmental biology and transgenerational inheritance. Birth Defects Res C Embryo Today. 2011;93:51–5. https://doi.org/10.1002/bdrc.20199
  • From AM, Leibson CL, Bursi F et al. Diabetes in heart failure: prevalence and impact on outcome in the population. Am J Med. 2006;119:591–9. https://doi.org/10.1016/j.amjmed.2006.05.024
  • Liu CF, Tang WHW. Epigenetics in cardiac hypertrophy and heart failure. Basic Transl Sci. 2019;4:976–93. https://doi.org/10.1016/j.jacbts.2019.05.011
  • Bui AL, Horwich TB, Fonarow GC. Epidemiology and risk profile of heart failure. Nat Rev Cardiol. 2011;30:30–41. https://doi.org/10.1038/nrcardio.2010.165
  • Rich MW. Heart failure in the 21st century: a cardiogeriatric syndrome. J Gerontol A Biol Sci Med Sci. 2001;56:M88–96. https://doi.org/10.1093/gerona/56.2.M88
  • Backs J, Olson EN. Control of cardiac growth by histone acetylation/ deacetylation. Circ Res. 2006;98:15–24. https://doi.org/10.1161/01.RES.0000197782.21444.8f
  • Frey N, Katus HA, Olson EN, Hill JA. Hypertrophy of the heart: a new therapeutic target? Circulation. 2004; 109:1580–9. doi:10.1161/01.CIR.0000120390.68287.BB
  • Hill JA, Olson EN, Biology M-L. Mechanisms of disease cardiac plasticity. N Engl J Med. 2008;58:1370–80. https://doi.org/10.1056/NEJMra072139
  • Duygu B, de Windt LJ, da Costa Martins PA. Targeting microRNAs in heart failure. Trends Cardiovasc Med. 2016;26:99–110. https://doi.org/10.1016/j.tcm.2015.05.008
  • Ganesan A. Multitarget drugs: an epigenetic epiphany. ChemMedChem. 2016;11:1227–41. https://doi.org/10.1002/cmdc.201500394
  • Madsen A, Höppner G, Krause J et al. An important role for DNMT3amediated DNA methylation in cardiomyocyte metabolism and contractility. Circulation. 2020;142:1562–78. https://doi.org/10.1161/CIRCULATIONAHA.119.044444
  • Stenzig J, Schneeberger Y, Löser A et al. Pharmacological inhibition of DNA methylation attenuates pressure overload-induced cardiac hypertrophy in rats. J Mol Cell Cardiol. 2018;120:53–63. https://doi.org/10.1016/j.yjmcc.2018.05.012
  • Gnyszka A, Jastrzebski Z, Flis S. DNA methyltransferase inhibitors and their emerging role in epigenetic therapy of cancer. Anticancer Res. 2013;33:2989–96.
  • Fraineau S, Palii CG, Allan DS, Brand M. Epigenetic regulation of endothelial-cell-mediated vascular repair. FEBS J. 2015;282:1605–29. https://doi.org/10.1111/febs.13183
  • Plácido R, Heinonen IHA, Volpe M et al. Microvascular dysfunction in heart failure with preserved ejection fraction. Front Physiol. 2018;10:1347. https://doi.org/10.3389/fphys.2019.01347
  • Rajan A, Shi H, Xue B. Class I and II histone deacetylase inhibitors differentially regulate thermogenic gene expression in brown adipocytes open. Sci Rep. 2018;8:13072. https://doi.org/10.1038/s41598-018-31560-w
  • Napoli C, Benincasa G, Donatelli F, Ambrosio G. Precision medicine in distinct heart failure phenotypes: focus on clinical epigenetics. Am Heart J. 2020;224:113–28. https://doi.org/10.1016/j.ahj.2020.03.007
  • Wang Y, Miao X, Liu Y et al. Dysregulation of histone acetyltransferases and deacetylases in cardiovascular diseases. Oxid Med Cell Longev. 2014;2014:641979. https://doi.org/10.1155/2014/641979
  • Kong Y, Tannous P, Lu G et al. Suppression of class I and II histone deacetylases blunts pressure-overload cardiac hypertrophy. Circulation. 2006;113:2579–88. https://doi.org/10.1161/CIRCULATIONAHA.106.625467
  • Granger A, Abdullah I, Huebner F et al. Histone deacetylase inhibition reduces myocardial ischemia-reperfusion injury in mice. FASEB J.2008;22:3549–60. https://doi.org/10.1096/fj.08-108548
  • Xie M, Kong Y, Tan W et al. Histone deacetylase inhibition blunts ischemia/reperfusion injury by inducing cardiomyocyte autophagy. Circulation. 2014;129:1139–51. https://doi.org/10.1161/CIRCULATIONAHA.113.002416
  • Kee HJ, Sohn IS, Nam KI et al. Inhibition of histone deacetylation blocks cardiac hypertrophy induced by angiotensin II infusion and aortic banding. Circulation. 2006 Jan 3;113(1):51-59. https://doi.org/10.1161/CIRCULATIONAHA.105.559724
  • Wallner M, Eaton DM, Berretta RM et al. HDAC inhibition improves cardiopulmonary function in a feline model of diastolic dysfunction. Sci Transl Med. 2020;12:eaay7205. https://doi.org/10.1126/scitranslmed.aay7205
  • Testai L, Sestito S, Martelli A et al. Synthesis and pharmacological characterization of mitochondrial KATP channel openers with enhanced mitochondriotropic effects. Bioorgan Chem. 2021;107:104572. https://doi.org/10.1016/j.bioorg.2020.104572
  • Kelly WK, Marks P, Richon VM. CCR 20th anniversary commentary: vorinostat–gateway to epigenetic therapy. Clin Cancer Res. 2015;21:2198–200. https://doi.org/10.1158/1078-0432.CCR-14-2556
  • Ho TCS, Chan AHY, Ganesan A. Thirty years of HDAC inhibitors: 2020 insight and hindsight. J Med Chem Am Chem Soc. 2020;63:12460–84. https://doi.org/10.1021/acs.jmedchem.0c00830
  • Jeong MY, Lin YH, Wennersten SA et al. Histone deacetylase activity governs diastolic dysfunction through a nongenomic mechanism. Sci Transl Med. 2018;10:eaao0144. https://doi.org/10.1126/scitranslmed.aao0144
  • Gillette T.G. HDAC inhibition in the heart: erasing hidden fibrosis. Circulation.2021;143(19):1891-1893. https://doi.org/10.1161/CIRCULATIONAHA.121.054262
  • Travers JG, Wennersten SA, Peña B, Bagchi RA, Smith HE, Hirsch RA, McKinsey TA. HDAC inhibition reverses preexisting diastolic dysfunction and blocks covert extracellular matrix remodeling. Circulation.2021;143(19):1874-1890. https://doi.org/10.1161/CIRCULATIONAHA.120.046462
  • Mattson RH, Cramer JA, Williamson PD, Novelly RA. Valproic acid in epilepsy: clinical and pharmacological effects. Ann Neurol. 1978;3:20–5. https://doi.org/10.1002/ana.410030105
  • Mokhtarani M, Diaz GA, Rhead W et al. Urinary phenylacetylglutamine as dosing biomarker for patients with urea cycle disorders. Mol Genet Metab. 2012;107:308–14. https://doi.org/10.1016/j.ymgme.2012.08.006 44. Tian S, Lei I, Gao W et al. HDAC inhibitor valproic acid protects heart function through Foxm1 pathway after acute myocardial infarction. EBioMedicine. 2019;39:83–94. https://doi.org/10.1016/j.ebiom.2018.12.003
  • Subramanian U, Kumar P, Mani I et al. Retinoic acid and sodium butyrate suppress the cardiac expression of hypertrophic markers and proinflammatory mediators in Npr1 gene-disrupted haplotype mice. Physiol Genomics. 2016;48:477–90. https://doi.org/10.1152/physiolgenomics.00073.2015
  • Chan-Penebre E, Kuplast KG, Majer CR et al. A selective inhibitor of PRMT5 with in vivo and in vitro potency in MCL models. Nat Chem Biol. 2015;11:432–7. https://doi.org/10.1038/nchembio.1810
  • Morera L, Lübbert M, Jung M. Targeting histone methyltransferases and demethylases in clinical trials for cancer therapy. Clin Epigenet. 2016;8:57. https://doi.org/10.1186/s13148-016-0223-4
  • Guo Y, Su Z-Y, Kong A-NT. Current perspectives on epigenetic modifications by dietary chemopreventive and herbal phytochemicals. Curr Pharmacol Rep. 2015;1:245–57. https://doi.org/10.1007/s40495-015-0023-0
  • Andrieu G, Belkina AC, Denis GV. Clinical trials for BET inhibitors run ahead of the science. Drug Discov Today Technol. 2016;19:45–50. https://doi.org/10.1016/j.ddtec.2016.06.004
  • Kalow W. Pharmacogenetics and pharmacogenomics: origin, status, and the hope for personalized medicine. Pharmacogenomics J. 2006;6:162–5. https://doi.org/10.1038/sj.tpj.6500361
  • Shi J, Vakoc CR. The mechanisms behind the therapeutic activity of BET bromodomain inhibition. Mol Cell Cell Press. 2014;54:728–36. https://doi.org/10.1016/j.molcel.2014.05.016
  • Borck PC, Guo LW, Plutzky J. BET epigenetic reader proteins in cardiovascular transcriptional programs. Circ Res. 2020;126:1190–208. https://doi.org/10.1161/CIRCRESAHA.120.315929
  • Nicholls SJ, Ray KK, Johansson JO et al. Selective BET protein inhibition with apabetalone and cardiovascular events: a pooled analysis of trials in patients with coronary artery disease. Am J Cardiovasc Drugs. 2018;18:109–15. https://doi.org/10.1007/s40256-017-0250-3
  • Nicholls SJ, Schwartz GG, Buhr KA et al. Apabetalone and hospitalization for heart failure in patients following an acute coronary syndrome: a prespecified analysis of the BETonMACE study. Cardiovasc Diabetol. 2021;20:13. https://doi.org/10.1186/s12933-020-01199-x
  • Tsujikawa LM, Fu L, Das S et al. Apabetalone (RVX-208) reduces vascular inflammation in vitro and in CVD patients by a BET-dependent epigenetic mechanism. Clin Epigenet. 2019;11:102. https://doi.org/10.1186/s13148-019-0696-z
  • Brandts J, Ray KK. Apabetalone – BET protein inhibition in cardiovascular disease and type 2 diabetes. Future Cardiol. 2020;16:385–95. https://doi.org/10.2217/fca-2020-0017
  • Chioccioli M, Roy S, Rigby K et al. A lung targeted miR-29 mimic as a therapy for pulmonary fibrosis. bioRxiv [Preprint]. 2021. https://doi.org/10.1101/2021.12.22.473724
  • van Rooij E, Sutherland LB, Thatcher JE et al. Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis. Proc Natl Acad Sci USA. 2008;105:13027–32. https://doi.org/10.1073/pnas.0805038105
  • Landmesser U, Poller W, Tsimikas S et al. From traditional pharmacological towards nucleic acid-based therapies for cardiovascular diseases. Eur Heart J. 2020;41:3884–99. https://doi.org/10.1093/eurheartj/ehaa229
  • Gargiulo P, Marzano F, Salvatore M, et al. MicroRNAs: diagnostic, prognostic and therapeutic role in heart failure — a review. ESC Heart Failure. 2023;10:2:753-761. https://doi.org/10.1002/ehf2.14153
  • Ruan W, Zhao F, Zhao S et al. Knockdown of long noncoding RNA MEG3 impairs VEGF-stimulated endothelial sprouting angiogenesis via modulating VEGFR2 expression in human umbilical vein endothelial cells. Gene. 2018;649:32–9. https://doi.org/10.1016/j.gene.2018.01.072
  • Leisegang MS, Fork C, Josipovic I et al. Long noncoding RNA MANTIS facilitates endothelial angiogenic function. Circulation. 2017;136:65–79. https://doi.org/10.1161/CIRCULATIONAHA.116.026991
  • Man HSJ, Sukumar AN, Lam GC et al. Angiogenic patterning by STEEL, an endothelial-enriched long noncoding RNA. Proc Natl Acad Sci USA. 2018;115:2401–6. https://doi.org/10.1073/pnas.1715182115
  • Zhang X, Tang X, Hamblin MH, Yin K-J. Long non-coding RNA malat1 regulates angiogenesis in hindlimb ischemia. Int J Mol Sci. 2018; 19:1723. doi:10.3390/ijms19061723
  • Simion V, Haemmig S, Feinberg MW. LncRNAs in vascular biology and disease. Vasc Pharmacol. 2019;114:145–56. https://doi.org/10.1016/j.vph.2018.01.003
  • Miano JM, Zheng D, Bell RD et al. Identification and initial functional characterization of a human vascular cell-enriched long noncoding RNA. Arterioscler Thromb Vasc Biol. 2014;34:1249–59. https://doi.org/10.1161/ATVBAHA.114.303240
  • Vance KW, Schulte C, Thum T et al. Long non-coding RNAs: at the heart of cardiac dysfunction? Front Physiol. 2019;10:30. https://doi.org/10.3389/fphys.2019.00030
  • Zhou W, Wang C, Chang J et al. RNA methylations in cardiovascular diseases, molecular structure, biological functions and regulatory roles in cardiovascular diseases. Front Pharmacol. 2021;12:722728. https://doi.org/10.3389/fphar.2021.722728
  • Qin Y, Li L, Luo E et al. Role of m6A RNA methylation in cardiovascular disease (review). Int J Mol Med. 2020;46:1958–72. https://doi.org/10.3892/ijmm.2020.4746
  • Zhang B, Xu Y, Cui X et al. Alteration of m6A RNA methylation in heart failure with preserved ejection fraction. Front Cardiovasc Med. 2021;8:647806. https://doi.org/10.3389/fcvm.2021.647806
  • Cao M, Luo H, Li D et al. Research advances on circulating long noncoding RNAs as biomarkers of cardiovascular diseases. Int J Cardiol. 2022;353:109–17. https://doi.org/10.1016/j.ijcard.2022.01.070
Еще
Статья обзорная
QR-код для установки приложения SciUp Наведите камеру и скачайте бесплатное приложение SciUp