Cover Image

Compound-Protein Interaction Analysis in Condition Following Cardiac Arrest

Mona Zamanian Azodi, Mostafa Rezaei-Tavirani, Majid Rezaei-Tavirani

Background: Cardiac arrest (CA) and differentially expressed genes (DEGs) relative to post-CA have attracted the attention of scientist to prevent damages, which threaten patients. In the present study, metabolites relevant to DEGs of post-CA condition investigated via protein-compound interaction to understand the pathological mechanisms in the human body. Materials and Methods: STITCH plug-in integrated into Cytoscape V.3.6.1 was used to detect the most significant interacting compounds relative to DEGs of pig’s brain after 5 minutes’ CA. The genes were obtained from the Gene Expression Omnibus database. The identified elements were considered for further evaluation and validation by literature survey. Result: Findings indicate that biochemical compounds including magnesium, calcium, glucose, glycerol, hydrogen, chloride, sulfate, and estradiol interact with DEGs in the two up- and down-regulated networks. Conclusion: The compounds interacting with DEGs are suitable subjects to analysis for re-regulation of the body after CA.[GMJ.2018;7:e1380]    


Heart Arrest; Protein Interaction Maps; Biomarkers; Transcriptome

Peng Y, Gregorich ZR, Valeja SG, Zhang H, Cai W, Chen Y-C, et al. Top-down proteomics reveals concerted reductions in myofilament and Z-disc protein phosphorylation after acute myocardial infarction. Molecular & Cellular Proteomics. 2014:mcp. M114. 040675.

Lemiale V, Dumas F, Mongardon N, Giovanetti O, Charpentier J, Chiche J-D, et al. Intensive care unit mortality after cardiac arrest: the relative contribution of shock and brain injury in a large cohort. Intensive care medicine. 2013;39(11):1972-80.


Zamanian-Azodi M, Rezaei-Tavirani M, Rostami-Nejad M, Tajik-Rostami F. New Molecular Aspects of Cardiac Arrest; Promoting Cardiopulmonary Resuscitation Approaches. Emergency. 2018;6(1):40.

Gul S, Huesgen K, Wang K, Mark K, Tyndall J. Prognostic utility of neuroinjury biomarkers in post out-of-hospital cardiac arrest (OHCA) patient management. Medical hypotheses. 2017;105:34-47.


Jacquet S, Yin X, Sicard P, Clark J, Kanaganayagam GS, Mayr M, et al. Identification of cardiac myosin-binding protein C as a candidate biomarker of myocardial infarction by proteomics analysis. Molecular & Cellular Proteomics. 2009;8(12):2687-99.

PMid:19721077 PMCid:PMC2816024

Spooner PM, Albert C, Benjamin EJ, Boineau R, Elston RC, George Jr AL, et al. Sudden cardiac death, genes, and arrhythmogenesis: consideration of new population and mechanistic approaches from a National Heart, Lung, and Blood Institute workshop, part II. Circulation. 2001;103(20):2447-52.


Lemaitre RN, Johnson CO, Hesselson S, Sotoodhenia N, McKnight B, Sitlani CM, et al. Common variation in fatty acid metabolic genes and risk of incident sudden cardiac arrest. Heart rhythm. 2014;11(3):471-7.

PMid:24418166 PMCid:PMC3966996

Nagase M, Sakurai A, Sugita A, Matsumoto N, Kubo A, Miyazaki Y, et al. Oxidative stress and abnormal cholesterol metabolism in patients with post-cardiac arrest syndrome. Journal of clinical biochemistry and nutrition. 2017;61(2):108-17.

PMid:28955127 PMCid:PMC5612819

Eun JW, Yang HD, Kim SH, Hong S, Park KN, Nam SW, et al. Identification of novel biomarkers for prediction of neurological prognosis following cardiac arrest. Oncotarget. 2017;8(10):16144.

PMid:28147324 PMCid:PMC5369953

Zamanian-Azodi M, Mortazavi-Tabatabaei SA, Mansouri V, Vafaee R. Metabolite-protein interaction (MPI) network analysis of obsessive-compulsive disorder (OCD) from reported metabolites. Arvand Journal of Health and Medical Sciences. 2016.

Chen L, Zhang Y-H, Zheng M, Huang T, Cai Y-D. Identification of compound–protein interactions through the analysis of gene ontology, KEGG enrichment for proteins and molecular fragments of compounds. Molecular Genetics and Genomics. 2016;291(6):2065-79.


Szklarczyk D, Morris JH, Cook H, Kuhn M, Wyder S, Simonovic M, et al. The STRING database in 2017: quality-controlled protein–protein association networks, made broadly accessible. Nucleic acids research. 2016:gkw937.


Floegel A, Kühn T, Sookthai D, Johnson T, Prehn C, Rolle-Kampczyk U, et al. Serum metabolites and risk of myocardial infarction and ischemic stroke: a targeted metabolomic approach in two German prospective cohorts. European journal of epidemiology. 2018;33(1):55-66.

PMid:29181692 PMCid:PMC5803284

Ward-Caviness CK, Xu T, Aspelund T, Thorand B, Montrone C, Meisinger C, et al. Improvement of myocardial infarction risk prediction via inflammation-associated metabolite biomarkers. Heart. 2017:heartjnl-2016-310789.

Elmer J, Callaway CW, editors. The brain after cardiac arrest. Seminars in neurology; 2017: Thieme Medical Publishers.

Opie LH. Metabolism of free fatty acids, glucose and catecholamines in acute myocardial infarction: relation to myocardial ischemia and infarct size. The American journal of cardiology. 1975;36(7):938-53.

Bolk J, Van der Ploeg T, Cornel J, Arnold A, Sepers J, Umans V. Impaired glucose metabolism predicts mortality after a myocardial infarction. International journal of cardiology. 2001;79(2-3):207-14.

Arnold SV, Lipska KJ, Li Y, McGuire DK, Goyal A, Spertus JA, et al. Prevalence of glucose abnormalities among patients presenting with an acute myocardial infarction. American heart journal. 2014;168(4):466-70. e1.

Gröber U, Schmidt J, Kisters K. Magnesium in prevention and therapy. Nutrients. 2015;7(9):8199-226.

PMid:26404370 PMCid:PMC4586582

Shafiq A, Goyal A, Jones PG, Sahil S, Hoffman M, Qintar M, et al. Serum magnesium levels and in-hospital mortality in acute myocardial infarction. Journal of the American College of Cardiology. 2017;69(22):2771-2.


Woods KL, Fletcher S. Long-term outcome after intravenous magnesium sulphate in suspected acute myocardial infarction: the second Leicester Intravenous Magnesium Intervention Trial (LIMIT-2). The Lancet. 1994;343(8901):816-9.

Cieslewicz A, Jankowski J, Korzeniowska K, Balcer-Dymel N, Jablecka A. The role of magnesium in cardiac arrhythmias. Journal of Elementology. 2013;18(2).

Noppens RR, Kofler J, Hurn PD, Traystman RJ. Dose-dependent neuroprotection by 17β-estradiol after cardiac arrest and cardiopulmonary resuscitation. Critical care medicine. 2005;33(7):1595-602.


Noppens RR, Kofler J, Grafe MR, Hurn PD, Traystman RJ. Estradiol after cardiac arrest and cardiopulmonary resuscitation is neuroprotective and mediated through estrogen receptor-β. Journal of Cerebral Blood Flow & Metabolism. 2009;29(2):277-86.

PMid:18957991 PMCid:PMC2682442

Lebesgue D, Chevaleyre V, Zukin RS, Etgen AM. Estradiol rescues neurons from global ischemia-induced cell death: multiple cellular pathways of neuroprotection. Steroids. 2009;74(7):555-61.

PMid:19428444 PMCid:PMC3029071

Nayler WG. The role of calcium in the ischemic myocardium. The American journal of pathology. 1981;102(2):262.

PMid:7008622 PMCid:PMC1903686

Yarmohammadi H, Uy-Evanado A, Reinier K, Rusinaru C, Chugh H, Jui J, et al., editors. Serum calcium and risk of sudden cardiac arrest in the general population. Mayo Clinic Proceedings; 2017: Elsevier.

Sejersted OM. Calcium controls cardiac function–by all means! The Journal of physiology. 2011;589(12):2919-20.

PMid:21676882 PMCid:PMC3139072

Rubenowitz E, Molin I, Axelsson G, Rylander R. Magnesium in drinking water in relation to morbidity and mortality from acute myocardial infarction. Epidemiology. 2000:416-21.


Urban P, Scheidegger D, Buchmann B, Barth D. Cardiac arrest and blood ionized calcium levels. Annals of internal medicine. 1988;109(2):110-3.


Mikkola TS, Tuomikoski P, Lyytinen H, Korhonen P, Hoti F, Vattulainen P, et al. Estradiol-based postmenopausal hormone therapy and risk of cardiovascular and all-cause mortality. Menopause. 2015;22(9):976-83.



  • There are currently no refbacks.