kpcczКомплексные проблемы сердечно-сосудистых заболеванийComplex Issues of Cardiovascular Diseases2306-12782587-9537Federal State Budgetary Institution “Research Institute for Complex Issues of Cardiovascular Diseases”10.17802/2306-1278-2020-9-4-88-94kpccz-786Research ArticleАНАЛИТИЧЕСКИЙ ОБЗОР. Патологическая физиологияREVIEWS. Pathological physiologyРоль стресса эндоплазматического ретикулума в атеросклерозеThe role of endoplasmic reticulum stress in atherosclerosishttps://orcid.org/0000-0001-7952-1068Багери ЕктаМ.Bagheri EktaM.

Багери Екта Марьям - младший научный сотрудник лаборатории клеточной и молекулярной патологии сердечно-сосудистой системы.

Ул. Цюрупы 3, Москва, 117418

Bagheri Yekta Maryam - junior researcher at the Laboratory of Cellular and Molecular Pathology of Cardiovascular System.

3, Tsyurupy St., Moscow, 117418

https://orcid.org/0000-0002-0312-3773СухоруковВ. Н.SukhorukovV. N.

Сухоруков Василий Николаевич - научный сотрудник лаборатории клеточной и молекулярной патологии сердечно-сосудистой системы.

Ул. Цюрупы 3, Москва, 117418

Sukhorukov Vasily N. - research assistant at the Laboratory of Cellular and Molecular Pathology of Cardiovascular System.

3, Tsyurupy St., Moscow, 117418

https://orcid.org/0000-0002-6649-7924МаркинА. М.MarkinA. M.

Маркин Александр Михайлович, научный сотрудник лаборатории клеточной и молекулярной патологии сердечно-сосудистой системы.

Ул. Цюрупы 3, Москва, 117418

Markin Alexander M. - research assistant at the Laboratory of Cellular and Molecular Pathology of Cardiovascular System.

alexander.markin.34@gmail.comhttps://orcid.org/0000-0003-0978-6444СобенинИ. А.SobeninI. A.

Собенин Игорь Александрович - доктор медицинских наук, руководитель лаборатории медицинской генетики.

Ул. 3-я Черепковская 15А, Москва, 121552

Sobenin Igor A. - PhD, Head of the Laboratory of Medical Genetics.

15A, 3rd Cherepkovskaya St., Moscow, 121552

https://orcid.org/0000-0002-6495-1628ОреховА. Н.OrekhovA. N.

Орехов Александр Николаевич - доктор биологических наук, ведущий научный сотрудник лаборатории клеточной и молекулярной патологии сердечно-сосудистой системы НИИ морфологии человека; заведующий лабораторией ангиопатологии НИИ общей патологии и патофизиологии.

Orekhov Alexander N. - PhD, Professor, Senior Researcher, Laboratory of Cellular and Molecular Pathology of Cardiovascular System, RI of Human Morphology; Head of the Laboratory of Angiopathology, RI of General Pathology and Pathophysiology.

3, Tsyurupy St., Moscow, 117418; 8, Baltiyskaya St., Moscow, 125315

Федеральное государственное бюджетное научное учреждение Научно-исследовательский институт морфологии человекаРоссияFederal State Budget Scientific Institution Research Institute of Human MorphologyRussian FederationФедеральное государственное бюджетное учреждение Национальный медицинский исследовательский центр кардиологи Министерства здравоохранения Российской ФедерацииРоссияFederal State Budgetary Institution National Medical Research Center for Cardiology of the Ministry of Healthcare of the Russian FederationRussian FederationФедеральное государственное бюджетное научное учреждение Научно-исследовательский институт морфологии человека; Федеральное государственное бюджетное научное учреждение Научно-исследовательский институт общей патологии и патофизиологииРоссияFederal State Budget Scientific Institution Research Institute of Human Morphology; Federal State Budget Scientific Institution Research Institute of General Pathology and PathophysiologyRussian Federation202018122020948894Copyright © Багери Екта М., Сухоруков В.Н., Маркин А.М., Собенин И.А., Орехов А.Н., 20202020Багери Екта М., Сухоруков В.Н., Маркин А.М., Собенин И.А., Орехов А.Н.Bagheri Ekta M., Sukhorukov V.N., Markin A.M., Sobenin I.A., Orekhov A.N.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.nii-kpssz.com/jour/article/view/786

В обзоре проанализированы причины стресса эндоплазматического ретикулума и связанные с ним внутриклеточные события. Обсуждается связь стресса эндоплазматического ретикулума с воспалением и накоплением липидов в клетках при атеросклерозе.

The review reports the main causes underlying endoplasmic reticulum stress and related intracellular phenomena. The relationship of endoplasmic reticulum stress with inflammation and lipid accumulation in cells during atherosclerosis is discussed.

стресс эндоплазматического ретикулумареакция несвернутых белковлипопротеины низкой плотностипенистые клеткимакрофагиатеросклерозendoplasmic reticulum stressunfolded protein responseldlfoam cellsmacrophagesatherosclerosisРабота проведена при финансовой поддержке Российского научного фонда (грант № 20-15-00364)ReferencesWilliams K.J., Tabas I. Atherosclerosis and inflammation. Science. 2002; 297: 521-522. doi: 10.1126/science.297.5581.521Williams K.J., Tabas I. Atherosclerosis and inflammation. Science. 2002; 297: 521-522. doi: 10.1126/science.297.5581.521Gargalovic P.S., Gharavi N.M., Clark M.J., Pagnon J, Yang W.P., He A., et al. The unfolded protein response is an important regulator of inflammatory genes in endothelial cells. Arterioscler. Thromb. Vasc. Biol. 2006; 26: 2490-2496. doi: 10.1161/01.ATV.0000242903.41158.a1Gargalovic P.S., Gharavi N.M., Clark M.J., Pagnon J, Yang W.P., He A., et al. The unfolded protein response is an important regulator of inflammatory genes in endothelial cells. Arterioscler. Thromb. Vasc. Biol. 2006; 26: 2490-2496. doi: 10.1161/01.ATV.0000242903.41158.a1Sobenin IA., Myasoedova V.A., Orekhov A.N. Phytoestrogen-Rich Dietary Supplements in Anti-Atherosclerotic Therapy in Postmenopausal Women. Curr Pharm Des. 2016;22(2):152-63. doi:10.2174/1381612822666151112150520Sobenin IA., Myasoedova V.A., Orekhov A.N. Phytoestrogen-Rich Dietary Supplements in Anti-Atherosclerotic Therapy in Postmenopausal Women. Curr Pharm Des. 2016;22(2):152-63. doi:10.2174/1381612822666151112150520Moore K. J., Sheedy F. J., Fisher E. A. Macrophages in atherosclerosis: a dynamic balance. Nature Reviews Immunology. 2013; 13 (10): 709-721.Moore K. J., Sheedy F. J., Fisher E. A. Macrophages in atherosclerosis: a dynamic balance. Nature Reviews Immunology. 2013; 13 (10): 709-721.Bouhlel M. A., Derudas B., Rigamonti E., Dievar R., Brozek J., Haulon S., et al. PPARy activation primes human monocytes into alternative M2 macrophages with antiinflammatory properties. Cell metabolism. 2007; 6 (2): 137143. doi: 10.1016/j.cmet.2007.06.010.Bouhlel M. A., Derudas B., Rigamonti E., Dievar R., Brozek J., Haulon S., et al. PPARy activation primes human monocytes into alternative M2 macrophages with antiinflammatory properties. Cell metabolism. 2007; 6 (2): 137143. doi: 10.1016/j.cmet.2007.06.010.VarinA., Gordon S. Alternative activation of macrophages: immune function and cellular biology. Immunobiology. 2009;214:630-41. doi:101016/j.imbio.200811.009.VarinA., Gordon S. Alternative activation of macrophages: immune function and cellular biology. Immunobiology. 2009;214:630-41. doi:101016/j.imbio.200811.009.Brocheriou I., Maouche S., Durand H., Braunersreuther V., Le Naour G., Gratchev A., Koskas F., Mach F., Kzhyshkowska J., Ninio E. Antagonistic regulation of macrophage phenotype by M-CSF and GM-CSF: implication in atherosclerosis. Atherosclerosis. 2011;214:316-24. doi:10.1016/j.atherosclerosis.2010.11.023.Brocheriou I., Maouche S., Durand H., Braunersreuther V., Le Naour G., Gratchev A., Koskas F., Mach F., Kzhyshkowska J., Ninio E. Antagonistic regulation of macrophage phenotype by M-CSF and GM-CSF: implication in atherosclerosis. Atherosclerosis. 2011;214:316-24. doi:10.1016/j.atherosclerosis.2010.11.023.Stoger J.L., Gijbels M.J., van der Velden S., Manca M., van der Loos C.M., Biessen E.A., Daemen M.J., Lutgens E., de Winther M.P. Distribution of macrophage polarization markers in human atherosclerosis. Atherosclerosis. 2012;225(2):461-8. doi: 101016/j.atherosclerosis.2012.09.013.Stoger J.L., Gijbels M.J., van der Velden S., Manca M., van der Loos C.M., Biessen E.A., Daemen M.J., Lutgens E., de Winther M.P. Distribution of macrophage polarization markers in human atherosclerosis. Atherosclerosis. 2012;225(2):461-8. doi: 101016/j.atherosclerosis.2012.09.013.Minamino T., Kitakaze M. ER stress in cardiovascular disease. Journal of Molecular and Cellular Cardiology. 2010; 48 (6): 1105-1110. doi:10.1016/j.yjmcc.2009.10.026Minamino T., Kitakaze M. ER stress in cardiovascular disease. Journal of Molecular and Cellular Cardiology. 2010; 48 (6): 1105-1110. doi:10.1016/j.yjmcc.2009.10.026Gaut J.R., Hendershot L.M. The modification and assembly of proteins in the endoplasmic reticulum. Curr Opin Cell Biol. 1993; 5: 589-595Gaut J.R., Hendershot L.M. The modification and assembly of proteins in the endoplasmic reticulum. Curr Opin Cell Biol. 1993; 5: 589-595Lee A.S. The glucose-regulated proteins: stress induction and clinical applications. Trends Biochem Sci. 2001; 26: 504510. doi:10.1016/s0968-0004(01)01908-9Lee A.S. The glucose-regulated proteins: stress induction and clinical applications. Trends Biochem Sci. 2001; 26: 504510. doi:10.1016/s0968-0004(01)01908-9Szegezdi E., Logue S.E., Gorman A.M., Samali A. Mediatirs of endoplasmic reticulum stresss-induced apoptosis. EMBO Rep. 2006; 7 (9): 880-885. doi:10.1038/sj.embor.7400779Szegezdi E., Logue S.E., Gorman A.M., Samali A. Mediatirs of endoplasmic reticulum stresss-induced apoptosis. EMBO Rep. 2006; 7 (9): 880-885. doi:10.1038/sj.embor.7400779Zhang K., Kaufman D.J. Identification and characterization of endoplasmic reticulum stress-induced apoptosis in vivo. Methods Enzymol. 2008; 442: 395-419.Zhang K., Kaufman D.J. Identification and characterization of endoplasmic reticulum stress-induced apoptosis in vivo. Methods Enzymol. 2008; 442: 395-419.Han J., Kaufman R.J. The role of ER stress in lipid metabolism and lipotoxicity. J Lipid Res. 2016; 57(8): 1329-38. doi: 10.1194/jlr.R067595Han J., Kaufman R.J. The role of ER stress in lipid metabolism and lipotoxicity. J Lipid Res. 2016; 57(8): 1329-38. doi: 10.1194/jlr.R067595Ron D., Walter P. Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol. 2007; 8: 519-529. doi:10.1038/nrm2199Ron D., Walter P. Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol. 2007; 8: 519-529. doi:10.1038/nrm2199Todd D.J., Lee A.H, Glimcher L.H. The endoplasmic reticulum stress response in immunity and autoimmunity. Nat Rev. Immunol. 2008; 8:663-674. doi:10.1038/nri2359Todd D.J., Lee A.H, Glimcher L.H. The endoplasmic reticulum stress response in immunity and autoimmunity. Nat Rev. Immunol. 2008; 8:663-674. doi:10.1038/nri2359Yoshida H., Matsui T., Yamamoto A., Okada T., Mori K. XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor. Cell. 2001; 107: 881-891. doi:10.1016/s0092-8674(01)00611-0Yoshida H., Matsui T., Yamamoto A., Okada T., Mori K. XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor. Cell. 2001; 107: 881-891. doi:10.1016/s0092-8674(01)00611-0Lee A.H., Iwakoshi N.N., Glimcher L.H. XBP-1 regulates a subset of endoplasmic reticulum resident chaperone genes in the unfolded protein response. Mol Cell Biol. 2003; 23: 7448-7459. doi:10.1128/mcb.23.21.7448-7459Lee A.H., Iwakoshi N.N., Glimcher L.H. XBP-1 regulates a subset of endoplasmic reticulum resident chaperone genes in the unfolded protein response. Mol Cell Biol. 2003; 23: 7448-7459. doi:10.1128/mcb.23.21.7448-7459Yamamoto K., Sato T., Matsui T., Sato M., Okada T., Yoshida H., et al. Transcriptional induction of mammalian ER quality control proteins is mediated by single or combined action of ATF6a and XBP1. Dev Cell. 2007; 13: 365-376. doi:10.1016/j.devcel.2007.07.018Yamamoto K., Sato T., Matsui T., Sato M., Okada T., Yoshida H., et al. Transcriptional induction of mammalian ER quality control proteins is mediated by single or combined action of ATF6a and XBP1. Dev Cell. 2007; 13: 365-376. doi:10.1016/j.devcel.2007.07.018Harding H.P., Zhang Y., Ron D. Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase. Nature. 1999; 397: 271-274. doi: 10.1038/16729Harding H.P., Zhang Y., Ron D. Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase. Nature. 1999; 397: 271-274. doi: 10.1038/16729Schroder M., Kaufman R.J. The mammalian unfolded protein response. Ann Rev Biochem. 2005; 74: 739-789. doi:10.1146/annurev.biochem.73.011303.074134Schroder M., Kaufman R.J. The mammalian unfolded protein response. Ann Rev Biochem. 2005; 74: 739-789. doi:10.1146/annurev.biochem.73.011303.074134Adachi Y., Yamamoto K., Okada T., Yoshida H., Harada A., Mori K. ATF6 is a transcription factor specializing in the regulation of quality control proteins in the endoplasmic reticulum. Cell Struct Funct. 2008; 33: 75-89. doi:10.1247/csf.07044Adachi Y., Yamamoto K., Okada T., Yoshida H., Harada A., Mori K. ATF6 is a transcription factor specializing in the regulation of quality control proteins in the endoplasmic reticulum. Cell Struct Funct. 2008; 33: 75-89. doi:10.1247/csf.07044Xiaoyun S., Schmitz G., Zhang M., Mackie R.I, Cann I.K. Chapter One Heterologous Gene Expression in Filamentous Fungi. Adv Appl Microbiol. 2012; 81:1-61. doi: 10.1016/B978-0-12-394382-8.00001-0.Xiaoyun S., Schmitz G., Zhang M., Mackie R.I, Cann I.K. Chapter One Heterologous Gene Expression in Filamentous Fungi. Adv Appl Microbiol. 2012; 81:1-61. doi: 10.1016/B978-0-12-394382-8.00001-0.Toth A., Nickson P., Mandl A. Endoplasmic reticulum stress as a novel therapeutic target in heart diseases. Cardiovasc Hematol Disord Drug Targets.2007; 7 (3): 205-218Toth A., Nickson P., Mandl A. Endoplasmic reticulum stress as a novel therapeutic target in heart diseases. Cardiovasc Hematol Disord Drug Targets.2007; 7 (3): 205-218Groenendyk J., Sreenivasaiah P.K., Kim do H. Biology of endoplasmic reticulum stress in the heart. Cir Res. 2010; 107 (10): 1185-1197. doi: 10.1161/CIRCRESAHA.110.227033Groenendyk J., Sreenivasaiah P.K., Kim do H. Biology of endoplasmic reticulum stress in the heart. Cir Res. 2010; 107 (10): 1185-1197. doi: 10.1161/CIRCRESAHA.110.227033Gregor M.F., Hotamisligil G.S. Thematic review series: Adipocyte Biology. Adipocyte stress: the endoplasmic reticulum and metabolic disease. J Lipid Res. 2007 ;48(9): 1905-14. doi:10.1194/jlr.R700007-JLR200Gregor M.F., Hotamisligil G.S. Thematic review series: Adipocyte Biology. Adipocyte stress: the endoplasmic reticulum and metabolic disease. J Lipid Res. 2007 ;48(9): 1905-14. doi:10.1194/jlr.R700007-JLR200Ozcan U., Cao Q., Yilmaz E., Lee A.H., Iwakoshi N.N., Ozdelen E., et al. Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science. 2004; 306:457461. doi:10.1126/science.1103160Ozcan U., Cao Q., Yilmaz E., Lee A.H., Iwakoshi N.N., Ozdelen E., et al. Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science. 2004; 306:457461. doi:10.1126/science.1103160Lee A.H., Scapa E.F., Cohen D.E., Glimcher L.H. Regulation of hepatic lipogenesis by the transcription factor XBP1. Science. 2008; 320:1492-1496. doi: 10.1126/science.1158042Lee A.H., Scapa E.F., Cohen D.E., Glimcher L.H. Regulation of hepatic lipogenesis by the transcription factor XBP1. Science. 2008; 320:1492-1496. doi: 10.1126/science.1158042Oyadomari S., Harding HP., Zhang Y., Oyadomari M., Ron D. Dephosphorylation of translation initiation factor 2alpha enhances glucose tolerance and attenuates hepatosteatosis in mice. Cell Metab. 2008; 7:520-532. doi:10.1016/j.cmet.2008.04.011Oyadomari S., Harding HP., Zhang Y., Oyadomari M., Ron D. Dephosphorylation of translation initiation factor 2alpha enhances glucose tolerance and attenuates hepatosteatosis in mice. Cell Metab. 2008; 7:520-532. doi:10.1016/j.cmet.2008.04.011Ota T., Gayet C., Ginsberg H.N., Clin J. Inhibition of apolipoprotein B100 secretion by lipid-induced hepatic endoplasmic reticulum stress in rodents. Invest. 2008; 118:316332. doi: 10.1172/JCI32752Ota T., Gayet C., Ginsberg H.N., Clin J. Inhibition of apolipoprotein B100 secretion by lipid-induced hepatic endoplasmic reticulum stress in rodents. Invest. 2008; 118:316332. doi: 10.1172/JCI32752Ozawa K., Miyazaki M., Matsuhisa M., Takano K., Nakatani Y, Hatazaki M., et al. The endoplasmic reticulum chaperone improves insulin resistance in type 2 diabetes. Diabetes. 2005; 54:657-663. doi:10.2337/diabetes.54.3.657Ozawa K., Miyazaki M., Matsuhisa M., Takano K., Nakatani Y, Hatazaki M., et al. The endoplasmic reticulum chaperone improves insulin resistance in type 2 diabetes. Diabetes. 2005; 54:657-663. doi:10.2337/diabetes.54.3.657Ozcan U., Yilmaz E., Ozcan L., Furuhashi M., Vaillancourt E., Smith R.O., et al. Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes. Science. 2006; 313:1137-1140. doi: 10.1126/science.1128294Ozcan U., Yilmaz E., Ozcan L., Furuhashi M., Vaillancourt E., Smith R.O., et al. Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes. Science. 2006; 313:1137-1140. doi: 10.1126/science.1128294Ramanadham S., Hsu F.F, Zhang S., Jin C., Bohrer A., Song H., et al. Apoptosis of insulin-secreting cells induced by endoplasmic reticulum stress is amplified by overexpression of group VIA calcium-independent phospholipase A2 (iPLA2 beta) and suppressed by inhibition of iPLA2 beta. Biochemistry. 2004; 43:918-930. doi:10.1021/bi035536mRamanadham S., Hsu F.F, Zhang S., Jin C., Bohrer A., Song H., et al. Apoptosis of insulin-secreting cells induced by endoplasmic reticulum stress is amplified by overexpression of group VIA calcium-independent phospholipase A2 (iPLA2 beta) and suppressed by inhibition of iPLA2 beta. Biochemistry. 2004; 43:918-930. doi:10.1021/bi035536mTessitore A., del P Martin M., Sano R., Ma Y., Mann L., Ingrassia A., et al. GM1-ganglioside-mediated activation of the unfolded protein response causes neuronal death in a neurodegenerative gangliosidosis. Mol Cell. 2004; 15:753-766. doi: 10.1016/j.molcel.2004.08.029Tessitore A., del P Martin M., Sano R., Ma Y., Mann L., Ingrassia A., et al. GM1-ganglioside-mediated activation of the unfolded protein response causes neuronal death in a neurodegenerative gangliosidosis. Mol Cell. 2004; 15:753-766. doi: 10.1016/j.molcel.2004.08.029Hotamisligil G. Endoplasmic reticulum stress and atherosclerosis. Nat Med. 2010; 16: 396-399. doi:10.1038/nm0410-396Hotamisligil G. Endoplasmic reticulum stress and atherosclerosis. Nat Med. 2010; 16: 396-399. doi:10.1038/nm0410-396Almeida SF., Fleming JV., Azevedo JE., Carmo-Fonseca M., de Sousa M. Stimulation of an unfolded protein response impairs MHC class I expression. J Immunol. 2007; 178: 36123619. doi: 10.4049/jimmunol.178.6.3612Almeida SF., Fleming JV., Azevedo JE., Carmo-Fonseca M., de Sousa M. Stimulation of an unfolded protein response impairs MHC class I expression. J Immunol. 2007; 178: 36123619. doi: 10.4049/jimmunol.178.6.3612Granados DP., Tanguay P.L, Hardy M.P, Caron E., de Verteuil D., Meloche S., et al. ER stress affects processing of MHC class I-associated peptides.BMC Immunol. 2009; 10: 10. doi:10.1186/1471-2172-10-10Granados DP., Tanguay P.L, Hardy M.P, Caron E., de Verteuil D., Meloche S., et al. ER stress affects processing of MHC class I-associated peptides.BMC Immunol. 2009; 10: 10. doi:10.1186/1471-2172-10-10Yang L., Jhaveri R., Huang J., Qi Y., Diehl A.M. Endoplasmic reticulum stress, hepatocyte CD1d and NKT cell abnormalities in murine fatty livers. Lab. Invest. 2007; 87: 927937. doi: 10.1038/labinvest.3700603Yang L., Jhaveri R., Huang J., Qi Y., Diehl A.M. Endoplasmic reticulum stress, hepatocyte CD1d and NKT cell abnormalities in murine fatty livers. Lab. Invest. 2007; 87: 927937. doi: 10.1038/labinvest.3700603Kelley J.L., Ozment T.R., Li C., Schweitzer J.B., Williams D.L. Scavenger receptor-A (CD204): A two-edged sword inhealth and disease. Critical Reviews in Immunology. 2014; 34 (3): 241—261. doi:10.1615/critrevimmunol.2014010267Kelley J.L., Ozment T.R., Li C., Schweitzer J.B., Williams D.L. Scavenger receptor-A (CD204): A two-edged sword inhealth and disease. Critical Reviews in Immunology. 2014; 34 (3): 241—261. doi:10.1615/critrevimmunol.2014010267Ji Y., Jian B., Wang N., Sun Y., Moya M.L., Phillips M.C., et al. Scavenger receptor BI promotes high density lipoprotein-mediated cellular cholesterol efflux. J Biol Chem. 1997; 272 (34): 20982-5. doi: 10.1074/jbc.272.34.20982Ji Y., Jian B., Wang N., Sun Y., Moya M.L., Phillips M.C., et al. Scavenger receptor BI promotes high density lipoprotein-mediated cellular cholesterol efflux. J Biol Chem. 1997; 272 (34): 20982-5. doi: 10.1074/jbc.272.34.20982Cojocaru E., Trandafirescu M., Leon M., Cotu^iu C., Foia L. Immunohistochemical expression of anti-CD68 antibody in atherosclerotic plaque. Rom J Morphol. Embryol. 2012; 53 (1): 61—66.Cojocaru E., Trandafirescu M., Leon M., Cotu^iu C., Foia L. Immunohistochemical expression of anti-CD68 antibody in atherosclerotic plaque. Rom J Morphol. Embryol. 2012; 53 (1): 61—66.Goyal T., Mitra S., Khaidakov M., Wang X., Singla S., Ding Z., et al. Current concepts of the role of oxidized LDL receptors in atherosclerosis. Cur Atheroscler Rep. 2012; 14: 150-159. doi:10.1007/s11883-012-0228-1Goyal T., Mitra S., Khaidakov M., Wang X., Singla S., Ding Z., et al. Current concepts of the role of oxidized LDL receptors in atherosclerosis. Cur Atheroscler Rep. 2012; 14: 150-159. doi:10.1007/s11883-012-0228-1Tabas I. Macrophage Apoptosis in Atherosclerosis: Consequences on Plaque Progression and the Role of Endoplasmic Reticulum Stress. Antioxid Redox Signal. 2009; 11 (9): 2333-2339. doi: 10.1089/ars.2009.2469Tabas I. Macrophage Apoptosis in Atherosclerosis: Consequences on Plaque Progression and the Role of Endoplasmic Reticulum Stress. Antioxid Redox Signal. 2009; 11 (9): 2333-2339. doi: 10.1089/ars.2009.2469Martmez M.S, Garda A., Luzardo E., Chavez-Castillo M., Olivar L.C., Salazar J., et al. Energetic metabolism in cardiomyocytes: molecular basis of heart ischemia and arrhythmogenesis. Vessel Plus. 2017; 1:130-4. doi: 10.20517/2574-1209.2017.34Martmez M.S, Garda A., Luzardo E., Chavez-Castillo M., Olivar L.C., Salazar J., et al. Energetic metabolism in cardiomyocytes: molecular basis of heart ischemia and arrhythmogenesis. Vessel Plus. 2017; 1:130-4. doi: 10.20517/2574-1209.2017.34Gargalovic P.S., Gharavi N.M., Clark M.J., Pagnon J., Yang W.P., He A., et al. The unfolded protein response is an important regulator of inflammatory genes in endothelial cells. Arterioscler Thromb Vasc Biol. 2006; 26: 2490-2496. doi: 10.1161/01.ATV.0000242903.41158.a1Gargalovic P.S., Gharavi N.M., Clark M.J., Pagnon J., Yang W.P., He A., et al. The unfolded protein response is an important regulator of inflammatory genes in endothelial cells. Arterioscler Thromb Vasc Biol. 2006; 26: 2490-2496. doi: 10.1161/01.ATV.0000242903.41158.a1Li Y., Schwabe R.F., DeVries-Seimon T., Yao P.M., Gerbod-Giannone M.C., Tall A.R., Davis R.J., Flavell R., Brenner D.A., Tabas I. Free cholesterol-loaded macrophages are an abundant source of tumor necrosis factor-а and interleukin-6: model of NF-kB- and MAP kinase-dependent inflammation in advanced atherosclerosis. J Biol Chem. 2005; 280: 21763-21772. doi: 10.1074/jbc.M501759200Li Y., Schwabe R.F., DeVries-Seimon T., Yao P.M., Gerbod-Giannone M.C., Tall A.R., Davis R.J., Flavell R., Brenner D.A., Tabas I. Free cholesterol-loaded macrophages are an abundant source of tumor necrosis factor-а and interleukin-6: model of NF-kB- and MAP kinase-dependent inflammation in advanced atherosclerosis. J Biol Chem. 2005; 280: 21763-21772. doi: 10.1074/jbc.M501759200Schroder M., Kaufman R.J. Divergent roles of IRE1alpha and PERK in the unfolded protein response. Curr Mol Med. 2006; 6 (1): 5-36. doi:10.2174/156652406775574569Schroder M., Kaufman R.J. Divergent roles of IRE1alpha and PERK in the unfolded protein response. Curr Mol Med. 2006; 6 (1): 5-36. doi:10.2174/156652406775574569Zhang K., Kaufman R.J. From endoplasmic-reticulum stress to the inflammatory response. Nature. 2008; 454 (7203): 455-462. doi: 10.1038/nature07203Zhang K., Kaufman R.J. From endoplasmic-reticulum stress to the inflammatory response. Nature. 2008; 454 (7203): 455-462. doi: 10.1038/nature07203Calvo M.J, Martmez M.S., Torres W., Chavez-Castillo M., Luzardo E., Villasmil N., et al. Omega-3 polyunsaturated fatty acids and cardiovascular health: a molecular view into structure and function. Vessel Plus. 2017; 1:116-128. doi:116-128.10.20517/2574-1209.2017.14Calvo M.J, Martmez M.S., Torres W., Chavez-Castillo M., Luzardo E., Villasmil N., et al. Omega-3 polyunsaturated fatty acids and cardiovascular health: a molecular view into structure and function. Vessel Plus. 2017; 1:116-128. doi:116-128.10.20517/2574-1209.2017.14Rius J., Guma M., Schachtrup C., Akassoglou K., Zinkernagel A.S., Nizet V., et al. NF-kB links innate immunity to the hypoxic response through transcriptional regulation of HIF-1a Nature. 2008; 453: 807-811. doi: 10.1038/nature06905Rius J., Guma M., Schachtrup C., Akassoglou K., Zinkernagel A.S., Nizet V., et al. NF-kB links innate immunity to the hypoxic response through transcriptional regulation of HIF-1a Nature. 2008; 453: 807-811. doi: 10.1038/nature06905Deng J., Lu P.D., Zhang Y., Scheuner D., Kaufman R.J., Sonenberg N., et al. Translational repression mediates activation of nuclear factor-KB by phosphorylated translation initiation factor 2. Mol Cell Biol. 2004; 24: 10161-10168. doi: 10.1128/MCB.24.23.10161-10168.2004Deng J., Lu P.D., Zhang Y., Scheuner D., Kaufman R.J., Sonenberg N., et al. Translational repression mediates activation of nuclear factor-KB by phosphorylated translation initiation factor 2. Mol Cell Biol. 2004; 24: 10161-10168. doi: 10.1128/MCB.24.23.10161-10168.2004Xu C., Bailly-Maitre B., Reed JC. Endoplasmic reticulum stress: cell life and death decisions. J Clin Invest. 2005; 115: 2656 -2664. doi:10.1172/JCI26373Xu C., Bailly-Maitre B., Reed JC. Endoplasmic reticulum stress: cell life and death decisions. J Clin Invest. 2005; 115: 2656 -2664. doi:10.1172/JCI26373Myasoedova V.A., Chistiakov D.A., Grechko A.V., Orekhov A.N. Matrix metalloproteinases in pro-atherosclerotic arterial remodeling. J Mol Cell Cardiol. 2018; 123:159-167. doi: 10.1016/j.yjmcc.2018.08.026.Myasoedova V.A., Chistiakov D.A., Grechko A.V., Orekhov A.N. Matrix metalloproteinases in pro-atherosclerotic arterial remodeling. J Mol Cell Cardiol. 2018; 123:159-167. doi: 10.1016/j.yjmcc.2018.08.026.Kim R., Emi M., Tanabe K., Murakami S. Role of the unfolded protein response in cell death. Apoptosis. 2006; 11: 5-13. doi: 10.1007/s10495-005-3088-0Kim R., Emi M., Tanabe K., Murakami S. Role of the unfolded protein response in cell death. Apoptosis. 2006; 11: 5-13. doi: 10.1007/s10495-005-3088-0Seimon T.A., Nadolski M.J., Liao X., Magallon J. Atherogenic lipids and lipoproteins trigger CD36-TLR2-dependent apoptosis in macrophages undergoing endoplasmic reticulum stress. Cell Metab. 2010; 12 (5):467-82. doi:10.1016/j.cmet.2010.09.010Seimon T.A., Nadolski M.J., Liao X., Magallon J. Atherogenic lipids and lipoproteins trigger CD36-TLR2-dependent apoptosis in macrophages undergoing endoplasmic reticulum stress. Cell Metab. 2010; 12 (5):467-82. doi:10.1016/j.cmet.2010.09.010Harding H.P., Zhang Y., Zeng H., Novoa I., Lu P.D., Calfon M., et al. An integrated stress response regulates amino acid metabolism and resistance to oxidative stress. Mol Cell 2003; 11 (3): 619-633. doi:10.1016/s1097-2765(03)00105-9Harding H.P., Zhang Y., Zeng H., Novoa I., Lu P.D., Calfon M., et al. An integrated stress response regulates amino acid metabolism and resistance to oxidative stress. Mol Cell 2003; 11 (3): 619-633. doi:10.1016/s1097-2765(03)00105-9Strassheim D., Karoor V., Stenmark K., Verin A., Gerasimovskaya E. A current view of G protein-coupled receptor-mediated signaling in pulmonary hypertension: finding opportunities for therapeutic intervention. Vessel Plus 2018; 2:21.Strassheim D., Karoor V., Stenmark K., Verin A., Gerasimovskaya E. A current view of G protein-coupled receptor-mediated signaling in pulmonary hypertension: finding opportunities for therapeutic intervention. Vessel Plus 2018; 2:21.Nishitoh H., Matsuzawa A., Tobiume K., Saegusa K., Takeda K., Inoue K., et al. ASK1 is essential for endoplasmic reticulum stress-induced neuronal cell death triggered by expanded polyglutamine repeats. Genes Dev. 2002; 16: 13451355. doi:10.1101/gad.992302Nishitoh H., Matsuzawa A., Tobiume K., Saegusa K., Takeda K., Inoue K., et al. ASK1 is essential for endoplasmic reticulum stress-induced neuronal cell death triggered by expanded polyglutamine repeats. Genes Dev. 2002; 16: 13451355. doi:10.1101/gad.992302Tabas I., Ron D. Integrating the mechanisms of apoptosis induced by endoplasmic reticulum stress. Nat Cell Biol. 2011 Mar; 13(3): 184-190. doi: 10.1038/ncb0311-184Tabas I., Ron D. Integrating the mechanisms of apoptosis induced by endoplasmic reticulum stress. Nat Cell Biol. 2011 Mar; 13(3): 184-190. doi: 10.1038/ncb0311-184Parolari A., Poggio P., Myasoedova V., Songia P., Bonalumi G., Pilozzi A., et al. Biomarkers in Coronary Artery Bypass Surgery: Ready for Prime Time and Outcome Prediction. Front Cardiovasc Med. 2016;2:39. doi: 10.3389/fcvm.2015.00039Parolari A., Poggio P., Myasoedova V., Songia P., Bonalumi G., Pilozzi A., et al. Biomarkers in Coronary Artery Bypass Surgery: Ready for Prime Time and Outcome Prediction. Front Cardiovasc Med. 2016;2:39. doi: 10.3389/fcvm.2015.00039

The authors declare that there are no conflicts of interest present.