Interação molecular entre o reparo tecidual via sinalização SDF-1/CXCR4 e a resposta inflamatória no infarto agudo do miocárdio com supradesnivelamento do segmento-ST

Authors

  • Melissa Kristochek da Silva Instituto de Cardiologia - Fundação Universitária de Cardiologia (IC/FUC), Porto Alegre, RS, Brasil
  • Marco Antônio de Bastiani Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brasil
  • Lucinara Dadda Dias Instituto de Cardiologia - Fundação Universitária de Cardiologia (IC/FUC), Porto Alegre, RS, Brasil
  • Raphael Boesche Guimarães Instituto de Cardiologia - Fundação Universitária de Cardiologia (IC/FUC), Porto Alegre, RS, Brasil
  • Marcela Corso Arend Instituto de Cardiologia - Fundação Universitária de Cardiologia (IC/FUC), Porto Alegre, RS, Brasil
  • Melissa Medeiros Markoski Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brasil

DOI:

https://doi.org/10.29327/multiscience.2022002

Keywords:

dano tecidual, eixo SDF-1/CXCR4, infarto do miocárdio, reparo cardíaco, inflamação

Abstract

A relação resposta inflamatória/dano isquêmico é pré-requisito para início do processo de adaptação do tecido cardíaco pós-infarto, contexto no qual a sinalização SDF-1/CXCR4 desempenha papel central no reparo tecidual. Este estudo objetivou investigar a modulação exercida pelo eixo SDF-1/CXCR4 sobre a resposta inflamatória após infarto agudo do miocárdio com elevação do segmento-ST (STEMI). Para tanto, desenvolvemos Redes Bayesianas a partir de dados de microarranjo (GEO) e avaliamos a expressão dos transcritos de interesse em pacientes com STEMI por qPCR. No contexto pró-inflamatório e agudo pós-infarto observamos forte relação entre proteínas de adesão endotelial e do infiltrado celular. No cenário crônico e anti-inflamatório, verificamos relação entre proteínas envolvidas com remodelamento tecidual e bloqueio de vias apoptóticas. Os níveis de expressão dos transcritos avaliados encontravam-se aumentados nos momentos iniciais pós-infarto. Conclui-se que os efeitos promovidos pela interação SDF-1/CXCR4 podem ser modulados segundo o perfil imunológico, influenciando diretamente nos seus efeitos adaptativos e cardioprotetores.

References

Anderson LR, Owens TW, Naylor MJ (2014) Structural and mechanical functions of integrins. Biophys Ver. DOI: 10.1007/s12551-013-0124-0

Ashburner M, Ball C, Blake J, et al. (2000) Gene ontology: tool for the unification of biology. Nat Genet. DOI: 10.1038/75556

Barandon L, Casassus F, Leroux L, Moreau C, Allières C, Lamazière JM, Dufourcq P, Couffinhal T, Duplàa C (2011) Secreted frizzled-related protein improves postinfarction scar formation through a modulation of inflammatory response. Arterioscler Thromb Vasc Biol. DOI: 10.1161/ATVBAHA.111.232280

Becker M, De Bastiani MA, Parisi MM, Guma FTCR, Markoski MM, Castro MAA, Kaplan MH, Barbé-Tuana FM & Klamt F (2015) Integrated Transcriptomics Establish Macrophage Polarization Signatures and have Potential Applications for Clinical Health and Disease. Scientific Reports. DOI: 10.1038/srep13351

Dobaczewski M, Gonzalez-Quesada C, Frangogiannis NG (2010) The extracellular matrix as a modulator of the inflammatory and reparative response following myocardial infarction. J Mol Cell Cardiol. DOI: 10.1016/j.yjmcc.2009.07.015

Flower DR (1999) Modelling G-protein-coupled receptors for drug design. Biochim Biophys Acta. DOI: 10.1016/s0304-4157(99)00006-4

Frangogiannis NG and Rosenzweig A (2012) Regulation of the inflammatory response in cardiac repair. Circ Res. DOI: 10.1161/CIRCRESAHA.111.243162

Frangogiannis NG (2015) Inflammation in cardiac injury, repair and regeneration. Curr Opin Cardiol. DOI: 10.1097/HCO.0000000000000158

Frantz S, Nahrendorf M (2014) Cardiac macrophages and their role in ischaemic heart disease. Cardiovasc Res. DOI:10.1093/cvr/cvu025

Gordon S, Martinez FO (2010) Alternative activation of macrophages: mechanism and functions. Immunity. DOI: 10.1016/j.immuni.2010.05.007

Hermans KC, Daskalopoulos EP and Blankesteijn WM (2012) Interventions in Wnt signaling as a novel therapeutic approach to improve myocardial infarct healing. Fibrogenesis Tissue Repair. DOI: 10.1186/1755-1536-5-16

Hu X, Dai S, Wu WJ, Tan W, Zhu X, Mu J, Guo Y, Bolli R, and Rokosh G (2007) Stromal cell derived factor-1 alpha confers protection against myocardial ischemia/reperfusion injury: role of the cardiac stromal cell derived factor-1 alpha CXCR4 axis. Circulation. DOI: 10.1161/CIRCULATIONAHA.106.672451

Kiliszek M, Burzynska B, Michalak M, Gora M, Winkler A, Maciejak A, Leszczynska A, Gajda E, Kochanowski J, Opolskit G (2012) Altered gene expression pattern in peripheral blood mononuclear cells in patients with acute myocardial infarction. PLoS One. DOI: org/10.1371/journal.pone.0050054

Lachtermacher S, Esporcatte BL, Montalvão F, Costa PC, Rodrigues DC, Belem L, Rabischoffisky A, Faria Neto HC, Vasconcellos R, Iacobas S, Iacobas DA, Dohmann HF, Spray DC, Goldenberg RC, Campos-de-Carvalho AC (2010) Cardiac gene expression and systemic cytokine profile are complementary in a murine model of post-ischemic heart failure. Braz J Med Biol Res. DOI: 10.1590/s0100-879x2010007500014

Liehn EA, Tuchscheerer N, Kanzler I, Drechsler M, Fraemohs L, Schuh A, Koenen RR, Zander S, Soehnlein O, Hristov M, Grigorescu G, Urs AO, Leabu M, Bucur I, Merx MW, Zernecke A, Ehling J, Gremse F, Lammers T, Kiessling F, Bernhagen J, Schober A, Weber C (2011) Double-edged role of the CXCL12/CXCR4 axis in experimental myocardial infarction. J Am Coll Cardiol. DOI: 10.1016/j.jacc.2011.08.033

Livak KJ and Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. DOI: 10.1006/meth.2001.1262

Maciejak A, Kiliszek M, Michalak M, Tulacz D, Opolski G, Matlak K, Dobrzycki S, Segiet A, Gora M, Burzynska B (2015) Gene expression profiling reveals potential prognostic biomarkers associated with the progression of heart failure. Genome Med. DOI: 10.1186/s13073-015-0149-z

Marchant DJ, Boyd JH, Lin DC, Granville DJ, Garmaroudi FS, McManus B (2012) Inflammation in myocardial diseases. Circ Res. DOI: 10.1161/CIRCRESAHA.111.243170

Neves SR, Ramand PT and Iyengar RR (2002) G protein pathways. Science. DOI: 10.1126/science.107155

Ni Y, Müller P, Wei L, Ji Y (2018) Bayesian graphical models for computational network biology. BMC Bioinformatics. DOI: 10.1186/s12859-018-2063-z

Okkenhaug K (2013) Signaling by the phosphoinositide 3-kinase family in immune cells. Annu Rev Immunol. DOI: 10.1146/annurev-immunol-032712-095946

Peterson MR, Haller SE, Ren J, Nair S, He G (2016) CARD9 as a potential target in cardiovascular disease. Drug Des Devel Ther. DOI: 10.2147/DDDT.S122508.

Pfeffer MA, Braunwald E (1990) Ventricular remodeling after myocardial infarction. Experimental observations and clinical implications. Circulation. DOI: 10.1161/01.cir.81.4.1161

Raychaudhuri S, Prinz WA (2010) The diverse functions of oxysterol-binding proteins. Annu Rev Cell Dev Biol. Doi: 10.1146/annurev.cellbio.042308.113334

Ren J, Yang M, Qi G, Zheng J, Jia L, Cheng J, Tian C, Li H, Lin X, Du J (2011) Proinflammatory protein CARD9 is essential for infiltration of monocytic fibroblast precursors and cardiac fibrosis caused by Angiotensin II infusion. Am J Hypertens. DOI: 10.1038/ajh.2011.42

Saxena A, Fish JE, White MD, Yu S, Smyth JW, Shaw RM, DiMaio JM, Srivastava D (2008) Stromal cell-derived factor-1alpha is cardioprotective after myocardial infarction. Circulatio. DOI: 10.1161/CIRCULATIONAHA.107.694992

Schulte G, Bryja V (2007) The Frizzled family of unconventional G-protein-coupled receptors. Trends Pharmacol Sci. DOI: 10.1016/j.tips.2007.09.001

Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES, Mesirov JP (2005) Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. DOI: 10.1073/pnas.0506580102

Suresh R, Li X, Chiriac A, Goel K, Terzic A, Perez-Terzic C, Nelson TJ (2014) Transcriptome from circulating cells suggests dysregulated pathways associated with long-term recurrent events following first-time myocardial infarction. J Mol Cell Cardiol. DOI: 10.1016/j.yjmcc.2014.04.017

Wang K, Zhao X, Kuang C, Qian D, Wang H, Jiang H, Deng M, Huang L (2012) Overexpression of SDF-1α enhanced migration and engraftment of cardiac stem cells and reduced infarcted size via CXCR4/PI3K pathway. PLoS One. DOI: 10.1371/journal.pone.0043922

Yu J, Li M, Qu Z, Yan D, Li D, Ruan Q (2010) SDF-1/CXCR4-mediated migration of transplanted bone marrow stromal cells toward areas of heart myocardial infarction through activation of PI3K/Akt. J Cardiovasc Pharmacol. DOI: 10.1097/FJC.0b013e3181d7a384

Zheng H, Fu G, Dai T, Huang H (2007) Migration of endothelial progenitor cells mediated by stromal cell-derived factor-1alpha/CXCR4 via PI3K/Akt/eNOS signal transduction pathway. J Cardiovasc Pharmacol. DOI: 10.1097/FJC.0b013e318093ec8f

Redes Bayesianas do perfil pró-inflamatório e anti-inflamatório pós-IAM

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Published

2021-11-29

How to Cite

Silva, M. K. da, de Bastiani, M. A., Dias, L. D., Guimarães, R. B., Corso Arend, M. ., & Medeiros Markoski, M. (2021). Interação molecular entre o reparo tecidual via sinalização SDF-1/CXCR4 e a resposta inflamatória no infarto agudo do miocárdio com supradesnivelamento do segmento-ST. Multidisciplinary Science Journal, 4, e2022002. https://doi.org/10.29327/multiscience.2022002

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Research Article