New approaches to pathogenetic anti-inflammatory therapy of cardiovascular diseases

Abstract

In recent years, new data have been obtained confirming the role of inflammation as the leading pathogenetic mechanism for the development of atherosclerosis and its complications. In addition, atherosclerosis is considered in the spectrum of atypical autoinflammatory diseases.

The aim of the paper is to highlight the role of inflammation in the development and progression of atherosclerosis and other cardiovascular diseases as well as to identify new therapeutic targets for the treatment of cardiovascular disease.

The search has been performed in the PubMed, e-library, Embase, ClinicalTrials.gov databases, using the keywords: “inflammation”, “NLRP3 inflammasome”, “TNF-α”, “IL-1 blocker”, “atherosclerosis”, “cardiovascular disease”. As a result, 210 references have obtained; the results of 15 clinical studies have been selected for the final analysis as well as 15 papers containing the results of original studies with access to the full text articles in Russian or English.

The analysis of literature sources revealed that inflammation plays a crucial role in the development of cardiovascular diseases, and modern anti-inflammatory therapy is a promising, pathogenetically justified strategy for the prevention and treatment of cardiovascular diseases.

Keywords

cardiovascular disease / atherosclerosis / inflammation / inflammasome / interleukin-1 / colchicine

References

[1] Strategiya razvitiya zdravookhraneniya v Rossiiskoi Federatsii na period do 2025 goda. Ukaz prezidenta Rossiiskoi Federatsii ot 06 iyunya 2019 g. No. 254. (In Russ.)

[2] Стратегия развития здравоохранения в Российской Федерации на период до 2025 года. Указ президента Российской Федерации от 06 июня 2019 г. № 254.

[3] Rossiya v tsifrakh 2019. Kratkii statisticheskii sbornik. Moscow: Rosstat; 2019. (In Russ.)

[4] Россия в цифрах 2019. Краткий статистический сборник. Москва: Росстат, 2019.

[5] Ezhov MV, Sergienko IV, Aronov DM, et al. Diagnostics and correction of lipid metabolism disorders in order to prevent and treat atherosclerosis. Russian recommendations VI revision. Journal of Atherosclerosis and Dyslipidaemias (JAD). 2017;3(28):5–22. (In Russ.)

[6] Ежов М.В., Сергиенко И.В., Аронов Д.М. и др. Диагностика и коррекция нарушений липидного обмена с целью профилактики и лечения атеросклероза. Российские рекомендации VI пересмотр // Атеросклероз и дислипидемии. 2017. Т. 3, № 28. С. 5–22.

[7] Ridker PM, Cushman M, Stampfer MJ, et al. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med. 1997;336(14):973–979. DOI: 10.1056/NEJM199704033361401

[8] Ridker P.M., Cushman M., Stampfer M.J. et al. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men // N. Engl. J. Med. 1997. Vol. 336, No. 14. P. 973–979. DOI: 10.1056/NEJM199704033361401

[9] Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med. 2000;342(12):836–843. DOI: 10.1056/NEJM200003233421202

[10] Ridker P.M., Hennekens C.H., Buring J.E., Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women // N. Engl. J. Med. 2000. Vol. 342, No. 12. P. 836–843. DOI: 10.1056/NEJM200003233421202

[11] Tabas I, Lichtman AH. Monocyte-macrophages and T cells in atherosclerosis. Immunity. 2017;47(4):621–634. DOI: 10.1016/j.immuni.2017.09.008

[12] Tabas I., Lichtman A.H. Monocyte-macrophages and T cells in atherosclerosis // Immunity. 2017. Vol. 47, No. 4. P. 621–634. DOI: 10.1016/j.immuni.2017.09.008

[13] Emini Veseli B, Perrotta P, De Meyer GRA, et al. Animal models of atherosclerosis. Eur J Pharmacol. 2017;816:3–13. DOI: 10.1016/j.ejphar.2017.05.010

[14] Emini Veseli B., Perrotta P., De Meyer G.R.A. et al. Animal models of atherosclerosis // Eur. J. Pharmacol. 2017. Vol. 816. P. 3–13. DOI: 10.1016/j.ejphar.2017.05.010

[15] Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020;41(1):111–188. DOI: 10.1093/eurheartj/ehz455

[16] Mach F., Baigent C., Catapano A.L. et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk // Eur. Heart J. 2020. Vol. 41, No. 1. P. 111–188. DOI: 10.1093/eurheartj/ehz455

[17] Mazurov VI, Belyaeva IB, Petrova MS, Bashkinov RA. Modern paradigm of treatment of hyperuricemia and gout in comorbid patients with the development of cardio-vascular pathology. Medical Council. 2020;(19):78–88. (In Russ.) DOI: 10.21518/2079-701X-2020-19-78-88

[18] Мазуров В.И., Беляева И.Б., Петрова М.С., Башкинов Р.А. Современная парадигма лечения гиперурикемии и подагры у коморбидных пациентов с развитием кардиоваскулярной патологии // Медицинский Совет. 2020. № 19. С. 78–88. DOI: 10.21518/2079-701X-2020-19-78-88

[19] Misawa T, Takahama M, Kozaki T, et al. Microtubule-driven spatial arrangement of mitochondria promotes activation of the NLRP3 inflammasome. Nat Immunol. 2013;14(5):454–460. DOI: 10.1038/ni.2550

[20] Misawa T., Takahama M., Kozaki T. et al. Microtubule-driven spatial arrangement of mitochondria promotes activation of the NLRP3 inflammasome // Nat. Immunol. 2013. Vol. 14, No. 5. P. 454–460. DOI: 10.1038/ni.2550

[21] Cronstein BN, Molad Y, Reibman J, et al. Colchicine alters the quantitative and qualitative display of selectins on endothelial cells and neutrophils. J Clin Invest. 1995;96(2):994–1002. DOI: 10.1172/JCI118147

[22] Cronstein B.N., Molad Y., Reibman J. et al. Colchicine alters the quantitative and qualitative display of selectins on endothelial cells and neutrophils // J. Clin. Invest. 1995. Vol. 96, No. 2. P. 994–1002. DOI: 10.1172/JCI118147

[23] Chia EW, Grainger R, Harper JL. Colchicine suppresses neutrophil superoxide production in a murine model of gouty arthritis: a rationale for use of low-dose colchicine. Br J Pharmacol. 2008;153(6):1288–1295. DOI: 10.1038/bjp.2008.20

[24] Chia E.W., Grainger R., Harper J.L. Colchicine suppresses neutrophil superoxide production in a murine model of gouty arthritis: a rationale for use of low-dose colchicine // Br. J. Pharmacol. 2008. Vol. 153, No. 6. P. 1288–1295. DOI: 10.1038/bjp.2008.20

[25] Marques-da-Silva C, Chaves MM, Castro NG, et al. Colchicine inhibits cationic dye uptake induced by ATP in P2X2 and P2X7 receptor-expressing cells: implications for its therapeutic action. Br J Pharmacol. 2011;163(5):912–926. DOI: 10.1111/j.1476-5381.2011.01254.x

[26] Marques-da-Silva C., Chaves M.M., Castro N.G. et al. Colchicine inhibits cationic dye uptake induced by ATP in P2X2 and P2X7 receptor-expressing cells: implications for its therapeutic action // Br. J. Pharmacol. 2011. Vol. 163, No. 5. P. 912–926. DOI: 10.1111/j.1476-5381.2011.01254.x

[27] Wang Y, Viollet B, Terkeltaub R, Liu-Bryan R. AMP-activated protein kinase suppresses urate crystal-induced inflammation and transduces colchicine effects in macrophages. Ann Rheum Dis. 2016;75(1):286–294. DOI: 10.1136/annrheumdis-2014-206074

[28] Wang Y., Viollet B., Terkeltaub R., Liu-Bryan R. AMP-activated protein kinase suppresses urate crystal-induced inflammation and transduces colchicine effects in macrophages // Ann. Rheum. Dis. 2016. Vol. 75, No. 1. P. 286–294. DOI: 10.1136/annrheumdis-2014-206074

[29] Crittenden DB, Lehmann RA, Schneck L, et al. Colchicine use is associated with decreased prevalence of myocardial infarction in patients with gout. J Rheumatol. 2012;39(7):1458–1464. DOI: 10.3899/jrheum.111533

[30] Crittenden D.B., Lehmann R.A., Schneck L. et al. Colchicine use is associated with decreased prevalence of myocardial infarction in patients with gout // J. Rheumatol. 2012. Vol. 39, No. 7. P. 1458–1464. DOI: 10.3899/jrheum.111533

[31] Grajek S, Michalak M, Urbanowicz T, Olasińska-Wiśniewska A. A meta-analysis evaluating the colchicine therapy in patients with coronary artery disease. Front Cardiovasc Med. 2021;8:740896. DOI: 10.3389/fcvm.2021.740896

[32] Grajek S., Michalak M., Urbanowicz T., Olasińska-Wiśniewska A. A meta-analysis evaluating the colchicine therapy in patients with coronary artery disease // Front. Cardiovasc. Med. 2021. Vol. 8. P. 740896. DOI: 10.3389/fcvm.2021.740896

[33] Fernández-Cuadros ME, Goizueta-San-Martin G, Varas-de-Dios B, et al. Colchicine-induced rhabdomyolysis: clinical, biochemical, and neurophysiological features and review of the literature. Clin Med Insights Arthritis Musculoskelet Disord. 2019;12:1179544119849883. DOI: 10.1177/1179544119849883

[34] Fernández-Cuadros M.E., Goizueta-San-Martin G., Varas-de-Dios B. et al. Colchicine-induced rhabdomyolysis: clinical, biochemical, and neurophysiological features and review of the literature // Clin. Med. Insights Arthritis Musculoskelet. Disord. 2019. Vol. 12. P. 1179544119849883. DOI: 10.1177/1179544119849883

[35] Sattar L, Memon RA, Ashfaq F, et al. Efficacy and safety of colchicine in prevention of secondary cardiovascular outcomes among patients with coronary vessel disease: a meta-analysis. Cureus. 2022;14(7):e26680. DOI: 10.7759/cureus.26680

[36] Sattar L., Memon R.A., Ashfaq F. et al. Efficacy and safety of colchicine in prevention of secondary cardiovascular outcomes among patients with coronary vessel disease: a meta-analysis // Cureus. 2022. Vol. 14, No. 7. P. e26680. DOI: 10.7759/cureus.26680

[37] Myachikova VYu, Titov VA, Maslyanskiy AL, Moiseeva OM. Idiopathic recurrent pericarditis — a paradigm shift? Russian Journal of Cardiology. 2019;(11):155–163. (In Russ.) DOI: 10.15829/1560-4071-2019-11-155-163

[38] Мячикова В.Ю., Титов В.А., Маслянский А.Л., Моисеева О.М. Идиопатический рецидивирующий перикардит — смена парадигмы? // Российский кардиологический журнал. 2019. Т. 11. С. 155–163. DOI: 10.15829/1560-4071-2019-11-155-163

[39] Maisch B, Seferović PM, Ristić AD, et al. Guidelines on the diagnosis and management of pericardial diseases executive summary; The Task force on the diagnosis and management of pericardial diseases of the European society of cardiology. Eur Heart J. 2004;25(7):587–610. DOI: 10.1016/j.ehj.2004.02.002

[40] Maisch B., Seferović P.M., Ristić A.D. et al. Guidelines on the diagnosis and management of pericardial diseases executive summary; The Task force on the diagnosis and management of pericardial diseases of the European society of cardiology // Eur. Heart J. 2004. Vol. 25, No. 7. P. 587–610. DOI: 10.1016/j.ehj.2004.02.002

[41] Myachikova V, Moiseeva O, Konradi A, et al. A retrospective analysis of colchicine in combination with NSAIDs therapy in patients with systemic form of adult-onset Still’s disease with serositis. Clin Exp Rheumatol. 2022;40(8):1474–1479. DOI: 10.55563/clinexprheumatol/1o41c8

[42] Myachikova V., Moiseeva O., Konradi A. et al. A retrospective analysis of colchicine in combination with NSAIDs therapy in patients with systemic form of adult-onset Still’s disease with serositis // Clin. Exp. Rheumatol. 2022. Vol. 40, No. 8. P. 1474–1479. DOI: 10.55563/clinexprheumatol/1o41c8

[43] Salih M, Smer A, Charnigo R, et al. Colchicine for prevention of post-cardiac procedure atrial fibrillation: Meta-analysis of randomized controlled trials. Int J Cardiol. 2017;243:258–262. DOI: 10.1016/j.ijcard.2017.04.022

[44] Salih M., Smer A., Charnigo R. et al. Colchicine for prevention of post-cardiac procedure atrial fibrillation: Meta-analysis of randomized controlled trials // Int. J. Cardiol. 2017. Vol. 243. P. 258–262. DOI: 10.1016/j.ijcard.2017.04.022

[45] Lennerz C, Barman M, Tantawy M, et al. Colchicine for primary prevention of atrial fibrillation after open-heart surgery: Systematic review and meta-analysis. Int J Cardiol. 2017;249:127–137. DOI: 10.1016/j.ijcard.2017.08.039

[46] Lennerz C., Barman M., Tantawy M. et al. Colchicine for primary prevention of atrial fibrillation after open-heart surgery: Systematic review and meta-analysis // Int. J. Cardiol. 2017. Vol. 249. P. 127–137. DOI: 10.1016/j.ijcard.2017.08.039

[47] Chung ES, Packer M, Lo KH, et al. Randomized, double-blind, placebo-controlled, pilot trial of infliximab, a chimeric monoclonal antibody to tumor necrosis factor-alpha, in patients with moderate-to-severe heart failure: results of the anti-TNF Therapy Against Congestive Heart Failure (ATTACH) trial. Circulation. 2003;107(25):3133–3140. DOI: 10.1161/01.CIR.0000077913.60364.D2

[48] Chung E.S., Packer M., Lo K.H. et al. Randomized, double-blind, placebo-controlled, pilot trial of infliximab, a chimeric monoclonal antibody to tumor necrosis factor-alpha, in patients with moderate-to-severe heart failure: results of the anti-TNF Therapy Against Congestive Heart Failure (ATTACH) trial // Circulation. 2003. Vol. 107, No. 25. P. 3133–3140. DOI: 10.1161/01.CIR.0000077913.60364.D2

[49] Toso A, Leoncini M, Magnaghi G, et al. Rationale and design of Colchicine on-admission to reduce inflammation in acute coronary syndrome (COLOR-ACS) study. J Cardiovasc Med (Hagerstown). 2023;24(1):52–58. DOI: 10.2459/JCM.0000000000001389

[50] Toso A., Leoncini M., Magnaghi G. et al. Rationale and design of Colchicine on-admission to reduce inflammation in acute coronary syndrome (COLOR-ACS) study // J. Cardiovasc. Med. (Hagerstown). 2023. Vol. 24, No. 1. P. 52–58. DOI: 10.2459/JCM.0000000000001389

[51] Akodad M, Lattuca B, Nagot N, et al. COLIN trial: Value of colchicine in the treatment of patients with acute myocardial infarction and inflammatory response. Arch Cardiovasc Dis. 2017;110(6–7):395–402. DOI: 10.1016/j.acvd.2016.10.004

[52] Akodad M., Lattuca B., Nagot N. et al. COLIN trial: Value of colchicine in the treatment of patients with acute myocardial infarction and inflammatory response // Arch. Cardiovasc. Dis. 2017. Vol. 110, No. 6–7. P. 395–402. DOI: 10.1016/j.acvd.2016.10.004

[53] McKnight AH, Katzenberger DR, Britnell SR. Colchicine in acute coronary syndrome: a systematic review. Ann Pharmacother. 2021;55(2):187–197. DOI: 10.1177/1060028020942144

[54] McKnight A.H., Katzenberger D.R., Britnell S.R. Colchicine in acute coronary syndrome: a systematic review // Ann. Pharmacother. 2021. Vol. 55, No. 2. P. 187–197. DOI: 10.1177/1060028020942144

[55] Dawson LP, Quinn S, Tong D, et al. Colchicine and quality of life in patients with acute coronary syndromes: results from the COPS randomized trial. Cardiovasc Revasc Med. 2022;44:53–59. DOI: 10.1016/j.carrev.2022.06.017

[56] Dawson L.P., Quinn S., Tong D. et al. Colchicine and quality of life in patients with acute coronary syndromes: results from the COPS randomized trial // Cardiovasc. Revasc. Med. 2022. Vol. 44. P. 53–59. DOI: 10.1016/j.carrev.2022.06.017

[57] Shah B, Pillinger M, Zhong H, et al. Effects of acute colchicine administration prior to percutaneous coronary intervention: colchicine-PCI randomized trial. Circ Cardiovasc Interv. 2020;13(4):e008717. DOI: 10.1161/CIRCINTERVENTIONS.119.008717

[58] Shah B., Pillinger M., Zhong H. et al. Effects of acute colchicine administration prior to percutaneous coronary intervention: colchicine-PCI randomized trial // Circ. Cardiovasc. Interv. 2020. Vol. 13, No. 4. P. e008717. DOI: 10.1161/CIRCINTERVENTIONS.119.008717

[59] Galli M, Princi G, Crea F, D’Amario D. Colchicine and risk of non-cardiovascular death in patients with coronary artery disease: a pooled analysis underling possible safety concern. Eur Heart J Cardiovasc Pharmacother. 2021;7(3):e18–e19. DOI: 10.1093/ehjcvp/pvaa137

[60] Galli M., Princi G., Crea F., D’Amario D. Colchicine and risk of non-cardiovascular death in patients with coronary artery disease: a pooled analysis underling possible safety concern // Eur. Heart J. Cardiovasc. Pharmacother. 2021. Vol. 7, No. 3. P. e18–e19. DOI: 10.1093/ehjcvp/pvaa137

[61] Opstal TSJ, Nidorf SM, Fiolet ATL, et al. Drivers of mortality in patients with chronic coronary disease in the low-dose colchicine 2 trial. Int J Cardiol. 2023;372:1–5. DOI: 10.1016/j.ijcard.2022.12.026

[62] Opstal T.S.J., Nidorf S.M., Fiolet A.T.L. et al. Drivers of mortality in patients with chronic coronary disease in the low-dose colchicine 2 trial // Int. J. Cardiol. 2023. Vol. 372. P. 1–5. DOI: 10.1016/j.ijcard.2022.12.026

[63] Opstal TSJ, van Broekhoven A, Fiolet ATL, et al. Long-term efficacy of colchicine in patients with chronic coronary disease: insights from LoDoCo2. Circulation. 2022;145(8):626–628. DOI: 10.1161/CIRCULATIONAHA.121.058233

[64] Opstal T.S.J., van Broekhoven A., Fiolet A.T.L. et al. Long-term efficacy of colchicine in patients with chronic coronary disease: insights from LoDoCo2 // Circulation. 2022. Vol. 145, No. 8. P. 626–628. DOI: 10.1161/CIRCULATIONAHA.121.058233

[65] Soehnlein O, Libby P. Targeting inflammation in atherosclerosis — from experimental insights to the clinic. Nat Rev Drug Discov. 2021;20(8):589–610. DOI: 10.1038/s41573-021-00198-1

[66] Soehnlein O., Libby P. Targeting inflammation in atherosclerosis — from experimental insights to the clinic // Nat. Rev. Drug Discov. 2021. Vol. 20, No. 8. P. 589–610. DOI: 10.1038/s41573-021-00198-1

[67] Abbate A, Toldo S, Marchetti C, et al. Interleukin-1 and the inflammasome as therapeutic targets in cardiovascular disease. Circ Res. 2020;126(9):1260–1280. DOI: 10.1161/CIRCRESAHA.120.315937

[68] Abbate A., Toldo S., Marchetti C. et al. Interleukin-1 and the inflammasome as therapeutic targets in cardiovascular disease // Circ. Res. 2020. Vol. 126, No. 9. P. 1260–1280. DOI: 10.1161/CIRCRESAHA.120.315937

[69] D’Amario D, Cappetta D, Cappannoli L, et al. Colchicine in ischemic heart disease: the good, the bad and the ugly. Clin Res Cardiol. 2021;110(10):1531–1542. DOI: 10.1007/s00392-021-01828-9

[70] D’Amario D., Cappetta D., Cappannoli L. et al. Colchicine in ischemic heart disease: the good, the bad and the ugly // Clin. Res. Cardiol. 2021. Vol. 110, No. 10. P. 1531–1542. DOI: 10.1007/s00392-021-01828-9

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