Efeito cardioprotetor dos inibidores da Fosfodiesterase 5 em modelo de Diabetes Mellitus experimental
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O Diabetes mellitus (DM) é considerado uma pandemia do século XXI e está frequentemente associado às doenças cardiovasculares (DCVs). O objetivo desta revisão integrativa foi analisar os efeitos cardioprotetores de inibidores da fosdodiesterase 5 (PDE5i) em modelos de diabetes experimental. Os artigos foram selecionados nas bases de dados PubMed, SciElo e LILACS no período de 2014 a 2019. Foram utilizados os seguintes descritores combinados com os operadores booleanos: Diabetes mellitus experimental AND Phosphodiesterase 5 inhibitors; Diabetic cardiomyopathies AND Phosphodiesterase 5 inhibitors. Foi obtida uma amostra inicial de 155 artigos, dos quais seis se enquadraram nos critérios para a síntese da revisão. Os estudos analisados evidenciaram que o tratamento com os PDEi5 em modelos experimentais, resultou em efeitos positivos sobre a função cardíaca e parâmetros metabólicos. Resultados semelhantes também foram observados em humanos. A redução da hipertrofia cardíaca, apoptose de cardiomiócitos, fatores pró-inflamatórios e estresse oxidativo e a modulação de fatores de transcrição envolvidos na homeostasia do diabetes, foram achados prevalentes entre os estudos. Os mecanismos de ação envolvidos na cardioproteção ainda não foram totalmente elucidados, contudo a restauração da via da guanosina monofato cíclica ativada (GMPc) pela Guanilato ciclase solúvel (GCs) via Óxido Nítrico (NO) foi um mecanismo comum entre os estudos.
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Referências
International Diabetes Federation (IDF). IDF diabetes atlas: Eighth edition 2017. Available from: https://diabetesatlas.org/upload/resources/previous/files/8/IDF_DA_8e-EN-final.pdf
Falcão-Pires I, Leite-Moreira AF. Diabetic cardiomyopathy: Understanding the molecular and cellular basis to progress in diagnosis and treatment. Heart Fail Rev. 2012;17(3):325-44. http://dx.doi.org/10.1007/s10741-011-9257-z
Bugger H, Abel ED. Molecular mechanisms of diabetic cardiomyopathy. Diabetologia. 2014;57(4):660-71. http://dx.doi.org/10.1007/s00125-014-3171-6
Gilca GE, Stefanescu G, Badulescu O, Tanase DM, Bararu I, Ciocoiu M. Diabetic cardiomyopathy: current approach and potential diagnostic and therapeutic targets. J Diabetes Res. 2017;2017:1-7. http://doi.org/10.1155/2017/1310265
Tian J, Zhao Y, Liu Y, Liu Y, Chen K, Lyu S. Roles and Mechanisms of Herbal Medicine for Diabetic Cardiomyopathy: Current Status and Perspective. Oxid Med Cell Longev. 2017;2017:8214541. http://doi.org/10.1155/2017/8214541
Carabetti JAM. Cardiomiopatía diabética. Rev Urug Cardiol. 2017;32(3):264-76. http://dx.doi.org/10.29277/RUC/32.3.7
Lukowski R, Krieg T, Rybalkin SD, Beavo J, Hofmann F. Turning on cGMP-dependent pathways to treat cardiac dysfunctions: Boom, bust, and beyond. Trends Pharmacol Sci. 2014;35(8):404-13. http://dx.doi.org/10.1016/j.tips.2014.05.003
Lu Z, Xu X, Hu X, Lee S, Traverse JH, Zhu G, et al. Oxidative stress regulates left ventricular PDE5 expression in the falling heart. Circulation. 2010;121(3):1474-8. http://doi.org/10.1161/circulationaha.109.906818
Das A, Durrant D, Salloum FN, Xi L, Kukreja RC. PDE5 inhibitors as therapeutics for heart disease, diabetes and cancer. Pharmacol Ther. 2015;147:12-21. http://doi.org/10.1016/j.pharmthera.2014.10.003
Zahabi A, Picard S, Fortin N, Reudelhuber TL, Deschepper CF. Expression of constitutively active guanylate cyclase in cardiomyocytes inhibits the hypertrophic effects of isoproterenol and aortic constriction on mouse hearts. J Biol Chem. 2003;278(48):47694-9. http://doi.org/10.1074/jbc.m309661200
Kishimoto I, Rossi K, Garbers DL. A genetic model provides evidence that the receptor for atrial natriuretic peptide (guanylyl cyclase-A) inhibits cardiac ventricular myocyte hypertrophy. Proc Natl Acad Sci. 2001;98(5):2703-6. http://doi.org/10.1073/pnas.051625598
Carvajal JA, Germain AM, Huidobro-Toro JP, Weiner CP. Molecular mechanism of cGMP-mediated smooth muscle relaxation. J Cell Physiol. 2000;184(3):409-20. http://doi.org/10.1002/1097-4652(200009)184:33.0.co;2-k
Polsinelli VB, Shah SJ. Advances in the pharmacotherapy of chronic heart failure with preserved ejection fraction: an ideal opportunity for precision medicine. Expert Opin Pharmacother. 2017;18(4):399-409. http://doi.org/10.1080/14656566.2017.1288717
Senni M, Paulus WJ, Gavazzi A, Fraser AG, Díez J, Solomon SD, et al. New strategies for heart failure with preserved ejection fraction: The importance of targeted therapies for heart failure phenotypes. Eur Heart J. 2014;35(40):2797-811. http://doi.org/10.1093/eurheartj/ehu204
Frey MK, Lang I. Tadalafil for the treatment of pulmonary arterial hypertension. Expert Opin Pharmacother. 2012;13(5):747-55. http://doi.org/10.1517/14656566.2012.662220
Melnyk BM, Fineout-Overholt E. Making the case for evidence-based practice and cultivating a spirit of inquiry. In: Melnyk BM, Fineout-Overholt E. Evidence-based practice in nursing & healthcare. A guide to best practice. 2nd ed. Philadelphia: Wolters Kluwer, 2011; p.3-24.
Whittemore R, Knafl K. The integrative review: updated methodology. J Adv Nurs. 2005;52(2):546-53. http://doi.org/10.1111/j.1365-2648.2005.03621.x
Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;7(6):e1000097. http://doi.org/10.1371/journal.pmed.1000097
Bacci L, Barbati SA, Colussi C, Aiello A, Isidori AM, Grassi C, et al. Sildenafil normalizes MALAT1 level in diabetic cardiomyopathy. Endocrine. 2018;62(1):259-62. http://doi.org/10.1007/s12020-018-1599-z
Barbati SA, Colussi C, Bacci L, Aiello A, Re A, Stigliano E, et al. Transcription factor CREM mediates high glucose response in cardiomyocytes and in a male mouse model of prolonged hyperglycemia. Endocrinology. 2017;158(7):2391-405. http://doi.org/10.1210/en.2016-1960
Venneri MA, Giannetta E, Panio G, De Gaetano R, Gianfrilli D, Pofi R, et al. Chronic inhibition of PDE5 limits pro-inflammatory monocyte-macrophage polarization in streptozotocin-induced diabetic mice. PLoS One. 2015;10(5):e0126580. http://doi.org/10.1371/journal.pone.0126580
Koka S, Aluri HS, Xi L, Lesnefsky EJ, Kukreja RC. Chronic inhibition of phosphodiesterase 5 with tadalafil attenuates mitochondrial dysfunction in type 2 diabetic hearts: potential role of NO/SIRT1/PGC-1α signaling. Am J Physiol Circ Physiol. 2014;306(11):1558-68. http://doi.org/10.1152/ajpheart.00865.2013
Goulopoulou S, Hannan JL, Matsumoto T, Ogbi S, Ergul A, Webb RC. Reduced vascular responses to soluble guanylyl cyclase but increased sensitivity to sildenafil in female rats with type 2 diabetes. Am J Physiol Circ Physiol. 2015;309(2):H297. http://doi.org/10.1152/ajpheart.00079.2015
Mátyás C, Németh BT, Oláh A, Török M, Ruppert M, Kellermayer D, et al. Prevention of the development of heart failure with preserved ejection fraction by the phosphodiesterase-5A inhibitor vardenafil in rats with type 2 diabetes. Eur J Heart Fail. 2017;19(3):326-36. http://doi.org/10.1002/ejhf.711
Varma A, Das A, Hoke NN, Durrant DE, Salloum FN, Kukreja RC. Anti-inflammatory and cardioprotective effects of tadalafil in diabetic mice. PLoS One. 2012;7(9):e45243. http://doi.org/e45243.10.1371/journal.pone.0045243
Koka S, Xi L, Kukreja RC. Chronic treatment with long acting phosphodiesterase-5 inhibitor tadalafil alters proteomic changes associated with cytoskeletal rearrangement and redox regulation in Type 2 diabetic hearts. Basic Res Cardiol. 2012;107(2):249. http://doi.org/10.1007/s00395-012-0249-5
Koka S, Das A, Salloum FN, Kukreja RC. Phosphodiesterase-5 inhibitor tadalafil attenuates oxidative stress and protects against myocardial ischemia/reperfusion injury in type 2 diabetic mice. Free Radic Biol Med. 2013;60:80-8. http://doi.org/10.1016/j.freeradbiomed.2013.01.031
Giannetta E, Isidori AM, Galea N, Carbone I, Mandosi E, Vizza CD, et al. Chronic Inhibition of cGMP phosphodiesterase 5A improves diabetic cardiomyopathy: a randomized, controlled clinical trial using magnetic resonance imaging with myocardial tagging. Circulation. 2012;125(19):2323-33. http://doi:10.1161/CIRCULATIONAHA.111.063412