Investigating Adipokine levels in the sera of patients with Myocardial Infarction in a 6-month follow up

Investigating Adipokine levels in the sera of patients with Myocardial Infarction in a 6-month follow up

Adipokines are peptides that regulate endothelial function, inflammation, blood pressure, and hemostasis. We measured Leptin, Adiponectin, Resistin and Adipsin in a cohort of 36 STEMI patients. Serum levels of Adipokines were measured in three time-points by a multiplex assay. A significant difference in Adipsin concentration between day-5 (T5) and day-180 (T180) post-MI was observed. Resistin levels decreased significantly from day 0 (T0) to T5 and T180. Adiponectin/Resistin ratio increased from T0 to T180. Leptin at T0 and T5 were higher in non-smokers. Adipsin at T0 was inversely correlated with heart rate, respiratory rate and pulse rate. Adiponectin/Resistin ratio at T180 negatively correlated with respiratory-rate. Adiponectin/Resistin ratio at T180 was higher in patients with grade-1 atrioventricular (AV) block. Anteroseptal hypokinesia (AH) correlated with Resistin at T0 and Adipsin at T5 while Leptin at T0 and T5 correlated with AH. Adiponectin/Resistin ratio at T180 was; however, lower in patients with AH. A decreasing trend in Resistin and its T0 association with AH plus correlation of Leptin at T0 and T5 with AH show the effect of Adipokines on mechanical complications after MI. We suggest that Adipokine networks have both beneficial and harmful effects and may be new cardiac biomarkers and/or drug targets.

___

  • 1. Benjamin EJ, Muntner P, et al. Heart Disease and Stroke Statistics-2019 Update: A Report From the American Heart Association. Circulation. 2019;139(10):e56-e528.
  • 2. Abbate A, Bussani R, et al. Right Ventricular Cardiomyocyte Apoptosis in Patients With Acute Myocardial Infarction of the Left Ventricular Wall. Am J Cardiol. 2008;102(6):658-62.
  • 3. Granger DN, Rodrigues SF, et al. Microvascular responses to cardiovascular risk factors. Microcirculation. 2010;17(3):192-205.
  • 4. Fasshauer M, Bluher M. Adipokines in health and disease. Trends Pharmacol Sci. 2015;36(7):461-70.
  • 5. Gualillo O. Elevated serum leptin concentrations induced by experimental acute inflammation. Life Sciences 2000;67:2433–41.
  • 6. Procaccini C, La Rocca C, et al. Leptin as immune mediator: Interaction between neuroendocrine and immune system. Dev Comp Immunol. 2017;66:120-9.
  • 7. Kontunen P, Vuolteenaho K, et al. Resistin is linked to inflammation, and leptin to metabolic syndrome, in women with inflammatory arthritis. Scand J Rheumatol. 2011;40(4):256-62.
  • 8. Mancuso P. The role of adipokines in chronic inflammation. Immunotargets Ther. 2016;5:47-56.
  • 9. Lehr S, Hartwig S, et al. Adipokines: a treasure trove for the discovery of biomarkers for metabolic disorders. Proteomics Clin Appl. 2012;6(1-2):91-101.
  • 10. Bluher M. Adipokines - removing road blocks to obesity and diabetes therapy. Mol Metab. 2014;3(3):230-40.
  • 11. Smekal A, Vaclavik J. Adipokines and cardiovascular disease: A comprehensive review. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2017;161(1):31-40.
  • 12. Ekmen N, Helvaci A, et al. Leptin as an important link between obesity and cardiovascular risk factors in men with acute myocardial infarction. Indian Heart J. 2016;68(2):132-7.
  • 13. Muse ED. The Association of Resistin with Cardiovascular Disease in The Multi-Ethnic Study of Atherosclerosis. Atherosclerosis. 2015;239(1):101-8.
  • 14. Lehrke M, Reilly MP, et al. An inflammatory cascade leading to hyperresistinemia in humans. PLoS Med. 2004;1(2):e45.
  • 15. Aquilante CL, Kosmiski LA, et al. Relationship between plasma resistin concentrations, inflammatory chemokines, and components of the metabolic syndrome in adults. Metabolism. 2008;57(4):494-501.
  • 16. Ntaios G, Gatselis NK, et al. Adipokines as mediators of endothelial function and atherosclerosis. Atherosclerosis. 2013;227(2):216-21.
  • 17. Kim M, Oh JK, et al. Role of resistin in cardiac contractility and hypertrophy. J Mol Cell Cardiol. 2008;45(2):270-80.
  • 18. Kaser S, Kaser A, et al. Resistin messenger-RNA expression is increased by proinflammatory cytokines in vitro. Biochem Biophys Res Commun. 2003;309(2):286-90.
  • 19. Calabro P, Samudio I, et al. Resistin promotes smooth muscle cell proliferation through activation of extracellular signal-regulated kinase 1/2 and phosphatidylinositol 3-kinase pathways. Circulation. 2004;110(21):3335-40.
  • 20. Kawanami D, Maemura K, et al. Direct reciprocal effects of resistin and adiponectin on vascular endothelial cells: a new insight into adipocytokine–endothelial cell interactions. Biochem Biophys Res Commun. 2004;314(2):415-9.
  • 21. Scherer PE. A Novel Serum Protein Similar to C1q, Produced Exclusively in adipocyte. J Biol Chem. 1995;45(10).
  • 22. Hu E. AdipoQ Is a Novel Adipose-specific Gene Dysregulated in Obesity. J Biol Chem. 1996;271(18):10697–703.
  • 23. B. Pyrzak, M. Ruminska, et al. Adiponectin as a biomarker of the metabolic syndrome in children and adolescents. Eur J Med Res. 2010;15.
  • 24. Murohara RSNOT. Adiponectin and Cardiovascular Disease. Circulation Journal. 2009;73:608-14.
  • 25. Luc G, Empana JP, et al. Adipocytokines and the risk of coronary heart disease in healthy middle aged men: the PRIME Study. Int J Obes (Lond). 2010;34(1):118-
  • 26. Cianflone K, Xia Z, et al. Critical review of acylation-stimulating protein physiology in humans and rodents. Biochimica et Biophysica Acta (BBA) - Biomembranes. 2003;1609(2):127-43.
  • 27. Piñeiro R, Iglesias MJ, et al. Adiponectin is synthesized and secreted by human and murine cardiomyocytes. FEBS letters. 2005;579(23):5163-9.
  • 28. Ou H-C, Lee W-J, et al. Aspirin prevents resistin-induced endothelial dysfunction by modulating AMPK, ROS, and Akt/eNOS signaling. J Vasc Surg. 2012;55(4):1104-15.
  • 29. Silswal N, Singh AK, et al. Human resistin stimulates the pro-inflammatory cytokines TNF-α and IL-12 in macrophages by NF-κB-dependent pathway. Biochem Biophys Res Commun. 2005;334(4):1092-101.
  • 30. Sarray S, Madan S, et al. Validity of adiponectin-to-leptin and adiponectin-to-resistin ratios as predictors of polycystic ovary syndrome. Fertil Steril. 2015;104(2):460-6.
  • 31. Singh P, Sridhar M, et al. Adiponectin-resistin index and its strong association with acute coronary syndrome in South Indian men. Inflamm Res. 2014;63(11):961-8.
  • 32. Chen BH, Song Y, et al. Circulating levels of resistin and risk of type 2 diabetes in men and women: results from two prospective cohorts. Diabetes care. 2009;32(2):329-34.
  • 33. Silha JV, Krsek M, et al. Plasma resistin, adiponectin and leptin levels in lean and obese subjects: correlations with insulin resistance. Eur J Endocrinol. 2003;149(4):331-5.
  • 34. Wyskida K, Franik G, et al. The levels of adipokines in relation to hormonal changes during the menstrual cycle in young, normal-weight women. Endocr Connect. 2017;6(8):892-900.
  • 35. Dafopoulos K, Sourlas D, et al. Blood ghrelin, resistin, and adiponectin concentrations during the normal menstrual cycle. Fertil Steril. 2009;92(4):1389-94.
  • 36. Reseland JE, Mundal HH, et al. Cigarette smoking may reduce plasma leptin concentration via catecholamines. Prostaglandins Leukot Essent Fatty Acids. 2005;73(1):43-9.
  • 37. Bokarewa MI, Erlandsson MC, et al. Smoking is associated with reduced leptin and neuropeptide Y levels and higher pain experience in patients with fibromyalgia. Mediators Inflamm. 2014;2014.
  • 38. Mohamad MM, Mohammad MA, et al. Effect of Smoking on Leptin Concentration in Normal Subjects and during Acute Myocardial Infarction. Med J Islamic World Acad Sci. 2009;17(2):75-80.
  • 39. Karaduman M, Oktenli C, et al. Leptin, soluble interleukin‐6 receptor, C‐reactive protein and soluble vascular cell adhesion molecule‐1 levels in human coronary atherosclerotic plaque. Clin Exp Immunol. 2006;143(3):452-7.
  • 40. Bucholz EM, Beckman AL, et al. Smoking status and life expectancy after acute myocardial infarction in the elderly. Heart. 2016;102(2):133-9.
  • 41. Haig C, Carrick D, et al. Current smoking and prognosis after acute ST-segment elevation myocardial infarction: new pathophysiological insights. JACC: Cardiovascular Imaging. 2019;12(6):993-1003.
  • 42. Shahini N, Michelsen AE, et al. The alternative complement pathway is dysregulated in patients with chronic heart failure. Sci Rep. 2017;7:42532.
  • 43. Ho JE, Lyass A, et al. Protein biomarkers of cardiovascular disease and mortality in the community. Journal of the American Heart Association. 2018;7(14):e008108.
  • 44. Ohtsuki T, Satoh K, et al. Identification of Adipsin as a Novel Prognostic Biomarker in Patients With Coronary Artery Disease. J Am Heart Assoc. 2019;8(23):e013716.
  • 45. Ermakov S, Azarbal F, et al. The associations of leptin, adiponectin and resistin with incident atrial fibrillation in women. Heart. 2016;102(17):1354-62.
  • 46. Fukui A, Takahashi N, et al. Role of leptin signaling in the pathogenesis of angiotensin II–mediated atrial fibrosis and fibrillation. Circ Arrhythm Electrophysio. 2013;6(2):402-9.
  • 47. Rienstra M, Sun JX, et al. Plasma resistin, adiponectin, and risk of incident atrial fibrillation: the Framingham Offspring Study. Am Heart J. 2012;163(1):119-24. e1.
  • 48. Pascual M, Pascual D, et al. Effects of isolated obesity on systolic and diastolic left ventricular function. Heart. 2003;89(10):1152-6.
  • 49. Finkelhor RS, Moallem M, et al. Characteristics and impact of obesity on the outpatient echocardiography laboratory. Am J Cardiol. 2006;97(7):1082-4.
  • 50. Shibata R, Ouchi N, et al. The role of adipokines in cardiovascular disease. J Cardiol. 2017;70(4):329-34.