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New Molecular Aspects of Cardiac Arrest; Promoting Cardiopulmonary Resuscitation Approaches

Mona Zamanian-Azodi, Mostafa Rezaei-Tavirani, Mohammad Rostami-Nejad, Fatemeh Tajik-Rostami




Introduction: Cardiopulmonary resuscitation (CPR) is a method to improve survival of patients with cardiac arrest. This study aimed to identify the key genes affected five minutes after cardiac arrest, hoping to elevate the efficacy of CPR.

Methods: In this bioinformatics study differentially expressed genes of six pigs were downloaded from GEO and screened. The significant and characterized genes were analyzed via calculating fold change and protein-protein interaction (PPI) networks. The crucial nodes were determined based on centrality parameters and their related biological processes were investigated via ClueGO.

Results: 17 significant up-regulated (LogFC ≥ 2) and 22 down-regulated (LogFC < -0.5) genes were detected. Transthyretin (TTR logFC = 4.59) and Gonadotropin-releasing hormone receptor (GNRHR logFC = 3.84) had higher logFC among up-regulated and down-regulated genes, respectively. The critical genes including four up-regulated and five down-regulated genes were detected from network analysis. GNRHR and Prolactin precursor (PRL) were among the most important down res 5 minutes after cardiac arrest and Beta-2 adrenergic receptor and Cadherin-1 were among the most important up regulated gens. 

Conclusion: The introduced potential biomarkers could reveal a new molecular aspect for CPR performance and pituitary gland protection was highlighted in this respect.   


Cardiac Arrest; Cardiopulmonary Resuscitation; Protein Interaction Maps; Gene Ontology, Biomarkers


Cave DM, Gazmuri RJ, Otto CW, Nadkarni VM, Cheng A, Brooks SC, et al. Part 7: CPR techniques and devices. Circulation. 2010;122(18 suppl 3):S720-S8.

Yeung J, Meeks R, Edelson D, Gao F, Soar J, Perkins GD. The use of CPR feedback/prompt devices during training and CPR performance: a systematic review. Resuscitation. 2009;80(7):743-51.

Zhao H, Li C-S, Gong P, Tang Z-R, Hua R, Mei X, et al. Molecular mechanisms of therapeutic hypothermia on neurological function in a swine model of cardiopulmonary resuscitation. Resuscitation. 2012;83(7):913-20.

Minamishima S, Bougaki M, Sips PY, De Yu J, Minamishima YA, Elrod JW, et al. Hydrogen sulfide improves survival after cardiac arrest and cardiopulmonary resuscitation via a nitric oxide synthase 3–dependent mechanism in mice. Circulation. 2009;120(10):888-96.

Böttiger BW, Motsch J, Braun V, Martin E, Kirschfink M. Marked activation of complement and leukocytes and an increase in the concentrations of soluble endothelial adhesion molecules during cardiopulmonary resuscitation and early reperfusion after cardiac arrest in humans. Critical care medicine. 2002;30(11):2473-80.

Minamishima S, Kida K, Tokuda K, Wang H, Sips PY, Kosugi S, et al. Inhaled Nitric Oxide Improves Outcomes After Successful Cardiopulmonary Resuscitation in MiceClinical Perspective. Circulation. 2011;124(15):1645-53.

Martijn C, Wiklund L. Effect of methylene blue on the genomic response to reperfusion injury induced by cardiac arrest and cardiopulmonary resuscitation in porcine brain. BMC medical genomics. 2010;3(1):27.

Navlakha S, Kingsford C. The power of protein interaction networks for associating genes with diseases. Bioinformatics. 2010;26(8):1057-63.

Nguyen T-P, Liu W-c, Jordán F. Inferring pleiotropy by network analysis: linked diseases in the human PPI network. BMC systems biology. 2011;5(1):179.

Karbalaei R, Allahyari M, Rezaei-Tavirani M, Asadzadeh-Aghdaei H, Zali MR. Protein-protein interaction analysis of Alzheimers disease and NAFLD based on systems biology methods unhide common ancestor pathways. Gastroenterology and Hepatology from bed to bench. 2018;11(1):27.

Safari-Alighiarloo N, Taghizadeh M, Rezaei-Tavirani M, Goliaei B, Peyvandi AA. Protein-protein interaction networks (PPI) and complex diseases. Gastroenterology and Hepatology from bed to bench. 2014;7(1):17.

Peyvandi H, Peyvandi AA, Safaei A, Azodi MZ, Rezaei-Tavirani M. Introducing Potential Key Proteins and Pathways in Human Laryngeal Cancer: A System Biology Approach. Iranian Journal of Pharmaceutical Research: IJPR. 2018;17(1):415.

Miclescu A, Basu S, Wiklund L. Cardio-cerebral and metabolic effects of methylene blue in hypertonic sodium lactate during experimental cardiopulmonary resuscitation. Resuscitation. 2007;75(1):88-97.

Bai B, Xie B, Pan Z, Shan L, Zhao J, Zhu H. Identification of candidate genes and long non-coding RNAs associated with the effect of ATP5J in colorectal cancer. International journal of oncology. 2018;52(4):1129-38.

Mlecnik B, Galon J, Bindea G. Comprehensive functional analysis of large lists of genes and proteins. Journal of proteomics. 2018;171:2-10.

Herbert J, Wilcox JN, Pham K-TC, Fremeau RT, Zeviani M, Dwork A, et al. Transthyretin A choroid plexus‐specific transport protein in human brain: The 1986 S. Weir Mitchell Award. Neurology. 1986;36(7):900-.

Jiang Z, Gibson JP, Archibald AL, Haley CS. The porcine gonadotropin-releasing hormone receptor gene (GNRHR): genomic organization, polymorphisms, and association with the number of corpora lutea. Genome. 2001;44(1):7-12.

Snyder EM, Turner ST, Johnson BD. β2-adrenergic receptor genotype and pulmonary function in patients with heart failure. Chest. 2006;130(5):1527-34.

Graziano F, Humar B, Guilford P. The role of the E-cadherin gene (CDH1) in diffuse gastric cancer susceptibility: from the laboratory to clinical practice. Annals of oncology. 2003;14(12):1705-13.

Pannone G, Santoro A, Feola A, Bufo P, Papagerakis P, Lo Muzio L, et al. The role of E-cadherin down-regulation in oral cancer: CDH1 gene expression and epigenetic blockage. Current Cancer Drug Targets. 2014;14(2):115-27.

Konishi Y, Stegmüller J, Matsuda T, Bonni S, Bonni A. Cdh1-APC controls axonal growth and patterning in the mammalian brain. Science. 2004;303(5660):1026-30.

Rodriguez-Rodriguez P, Almeida A, Bolaños JP. Brain energy metabolism in glutamate-receptor activation and excitotoxicity: role for APC/C-Cdh1 in the balance glycolysis/pentose phosphate pathway. Neurochemistry international. 2013;62(5):750-6.

Steegers-Theunissen RP, Obermann-Borst SA, Kremer D, Lindemans J, Siebel C, Steegers EA, et al. Periconceptional maternal folic acid use of 400 µg per day is related to increased methylation of the IGF2 gene in the very young child. PLoS One. 2009;4(11):e7845.

Brade T, Kumar S, Cunningham TJ, Chatzi C, Zhao X, Cavallero S, et al. Retinoic acid stimulates myocardial expansion by induction of hepatic erythropoietin which activates epicardial Igf2. Development. 2011;138(1):139-48.

Mehta SR, Yusuf S, Díaz R, Zhu J, Pais P, Xavier D, et al. Effect of glucose-insulin-potassium infusion on mortality in patients with acute ST-segment elevation myocardial infarction: the CREATE-ECLA randomized controlled trial. Jama. 2005;293(4):437-46.

Stellpflug SJ, Harris CR, Engebretsen KM, Cole JB, Holger JS. Intentional overdose with cardiac arrest treated with intravenous fat emulsion and high-dose insulin. Clinical toxicology. 2010;48(3):227-9.

La Rosa S, Celato N, Uccella S, Capella C. Detection of gonadotropin-releasing hormone receptor in normal human pituitary cells and pituitary adenomas using immunohistochemistry. Virchows Archiv. 2000;437(3):264-9.

Freeman ME, Kanyicska B, Lerant A, Nagy G. Prolactin: structure, function, and regulation of secretion. Physiological reviews. 2000;80(4):1523-631.

Cosowsky L, Rao SV, Macdonald GJ, Papkoff H, Campbell RK, Moyle WR. The groove between the α-and β-subunits of hormones with lutropin (LH) activity appears to contact the LH receptor, and its conformation is changed during hormone binding. Journal of Biological Chemistry. 1995;270(34):20011-9.

DOI: https://doi.org/10.22037/emergency.v6i1.21467


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