CRUCIAL MARKERS SHOWING THE RISK OF CORONARY ARTERY DISEASE IN OBESITY: ADMA AND NEOPTERIN
Abstract
Background: Obesity is responsible for high morbidity and mortality, both in developed and developing countries. It is associated with many chronic and metabolic diseases. Asymmetric dimethylarginine (ADMA) has been demonstrated to be a biomarker of endothelial dysfunction in humans and increased ADMA associated with cardiovascular disease (CVD) risk has been reported in many states. Neopterin (NP) produced by monocytes/macrophages in response to stimulation by interferon-gamma (IFN-g) is emphasized in recent findings. The current study aims to investigate ADMA and NP levels which may assume a role in guiding the early diagnosis of coronary artery disease in obesity. Methods: This is an original research study in which ADMA and NP levels of 50 patients (25 male/25 female) diagnosed with obesity were compared with those of 30 healthy individuals (15 male/15 female) as control. The high-performance liquid chromatography (HPLC) method was used while determining parameters. Results: ADMA and NP levels in obese individuals were found to be significantly higher than in those enrolled in the control. ADMA values were found to be higher in obese subjects (0.71±0.24 mmol/L) as compared with levels found in healthy subjects (0.58±0.16 mmol/L) (p<0.05). A significant increase of serum neopterin levels was found in obese subjects (8.8±3.5 mmol/L) as compared with controls (4.9±1.69 mmol/L) (p<0.05). Also, there was a strong positive correlation between NP and ADMA values in obese individuals (r=0.954). Conclusions: Our study revealed that obese subjects have higher ADMA and neopterin levels. These results demonstrated that both ADMA and NP levels may be potential risk factors for coronary heart disease in obesity.
References
Koliaki C, Liatis S, Kokkinos A. Obesity and cardiovascular disease: revisiting an old relationship. Metabolism 2019; 92: 98–107.
Poobalan A, Aucott L. Obesity Among Young Adults in Developing Countries: A Systematic Overview. Curr Obes Rep 2016; 5(1): 2–13.
Bhurosy T, Jeewon R. Overweight and obesity epidemic in developing countries: a problem with diet, physical activity, or socioeconomic status? Scientific World Journal 2014; 2014: 964236.
Longo M, Zatterale F, Naderi J, Parrillo L, Formisano P,
Raciti GA, Beguinot F, Miele C. Adipose Tissue Dysfunction as Determinant of Obesity-Associated Metabolic Complications. Int J Mol Sci 2019;20(9). pii: E2358. doi: 10.3390/ijms20092358.
Jackson VM, Breen DM, Fortin JP, Liou A, Kuzmiski JB, Loomis AK, Rives ML, Shah B, Carpino PA. Latest approaches for the treatment of obesity. Expert Opin Drug Discov 2015; 10(8): 825–39.
El Assar M, Angulo J, Santos-Ruiz M, Ruiz de Adana JC, Pindado ML, Sánchez-Ferrer A, Hernández A, Rodríguez-Mañas L. Asymmetric dimethylarginine (ADMA) elevation and arginase up-regulation contribute to endothelial dysfunction related to insulin resistance in rats and morbidly obese humans. J Physiol
; 594(11): 3045–60.
Barthelmes J, Nägele MP, Ludovici V, Ruschitzka F, Sudano I, Flammer AJ. Endothelial dysfunction in cardiovascular disease and Flammer syndrome–similarities and differences. EPMA J 2017; 8(2): 99–109.
Unuvar S, Tanrıverdi Z, Aslanhan H. Potential prognostic role of immune system activation marker neopterin in patients with type 2 diabetes. J Med Biochem 2018; 37: 465–9.
Popovic D, Lalic K, Jotic A, Milicic T, Bogdanovic J, or|evic M, Stankovic S, Jeremic V, Lalic NM. The inflammatory and hemostatic cardiovascular risk markers during acute hyperglycemic crisis in type 1 and type 2 diabetes. J Med Biochem 2019; 38: 126–33.
Avcı E, Coskun Cevher S, Cakır E, Yaman H, Bilgi C. Determination of oxidative stress and cellular immunity in patients with diabetic nephropathy and non-diabetic nephropathy being administered hemodialysis treatment due to chronic renal failure. Renal Failure 2014; 36 (5): 776–3.
Anderssohn M, Schwedhelm E, Lüneburg N, Vasan RS, Böger RH. Asymmetric dimethylarginine as a mediator of vascular dysfunction and a marker of cardiovascular disease and mortality: an intriguing interaction with diabetes mellitus. Diab Vasc Dis Res 2010; 7(2): 105–18.
Nageswara Rao GS, Gurumurthy P, E S, Cherian KM. The clinical and biochemical parameters in relation to the serum neopterin levels in Indian children and adolescents. J Clin Diagn Res 2013;7(4): 618–21.
Mangge H, Almer G, Truschnig-Wilders M, Schmidt A, Gasser R, Fuchs D. Inflammation, adiponectin, obesity and cardiovascular risk. Curr Med Chem 2010; 17(36): 4511–20.
Grammer TB, Fuchs D, Boehm BO, Winkelmann BR, Maerz W. Neopterin as a Predictor of Total and Cardiovascular Mortality in Individuals Undergoing Angiography in the Ludwigshafen Risk and Cardiovascular Health Study. Clin Chem 2009; 55(6): 1135–46.
Spencer ME, Jain A, Matteini A, Beamer BA, Wang NY, Leng SX, Punjabi NM, Walston JD, Fedarko NS. Serum levels of the immune activation marker neopterin change with age and gender and are modified by race, BMI, and percentage of body fat. J Gerontol A Biol Sci Med Sci 2010; 65(8): 858–65.
Avcı E, Coşkun Ş, Çakır E, Kurt Y, Akgül EÖ, Bilgi C. Relations between concentrations of asymmetric dimethylarginine and neopterin as potential risk factors for cardiovascular diseases in haemodialysis-treated patients. Ren Fail 2008; 30(8): 784–90.
Matsubara M, Maruoka S, Katayose S. Inverse relationship between plasma adiponectin and leptin concentrations in normal weight and obese women. Eur J Endocrinol 2002; 147(2):173–80.
Baskın Y, Yiğitbaşı T, Afacan G, Bağbozan Ş. İnsülin direnci olan erişkin kilolu ve obezlerde lipoprotein (a) ile lipid parametreleri. Türk Klinik Biyokimya Derg 2008; 6(2): 65–71.
Şentürk BA, Üstüner F, Aksu S, Sülek Z. Plasminojen Aktivatör Ünhibitör Tip I, İnsülin Direnci ve Android Obezite. Türk Klinik Biyokimya Derg 2005; 3(3):109–15.
Shuldiner AR, Yang R, Gong DW. Resistin, obesity and insulin resistance the emerging role of the adipocyte as an endocrine organ. N Engl J Med 2001; 345(18): 1345–6.
Liu X, Hou L, Xu D, Chen A, Yang L, Zhuang Y, Xu Y, Fassett JT, Chen Y. Effect of asymmetric dimethylarginine (ADMA) on heart failure development. Nitric Oxide 2016; 54: 73–81.
Dückelmann C, Mittermayer F, Haider DG, Altenberger J, Eichinger J, Wolzt M. Asymmetric dimethylarginine enhances cardiovascular risk prediction in patients with chronic heart failure. Arterioscler Thromb Vasc Biol 2007; 27(9): 2037–42.
Krzyzanowska K, Mittermayer F, Kopp HP, Wolzt M, Schernthaner G. Weight loss reduces circulating asymmetrical dimethylarginine concentrations in morbidly obese women. J Clin Endocrinol Metab 2004; 89(12): 6277–81.
Marliss EB, Chevalier S, Gougeon R, Morais JA, Lamarche M, Adegoke OA, Wu G. Elevations of plasma methylarginines in obesity and ageing are related to insulin sensitivity and rates of protein turnover. Diabetologia 2006; 49(2): 351–9.
Nakhjavani M, Karimi-Jafari H, Esteghamati A, Khalilzadeh O, Asgarani F, Ghadiri-Anari A. ADMA is a correlate of insulin resistance in early-stage diabetes independent of hs-CRP and body adiposity. Ann Endocrinol (Paris) 2010; 71(4): 303–8.
Milosevic D, Lukic Panin V. Relationship between hematological parameters and glycemic control in type 2 diabetes mellitus patients. J Med Biochem 2019; 39: 164–71.
Prieto D, Contreras C, Sánchez A. Endothelial dysfunction, obesity and insulin resistance. Curr Vasc Pharmacol 2014; 12(3): 412–26.
El Assar M, Ruiz de Adana JC, Angulo J, Pindado Martínez ML, Hernández Matías A, Rodríguez-Mañas L. Preserved endothelial function in human obesity in the absence of insulin resistance. J Transl Med 2013; 11: 263.
McLaughlin T, Stühlinger M, Lamendola C, Abbasi F, Bialek J, Reaven GM, Tsao PS. Plasma asymmetric dimethylarginine concentrations are elevated in obese insulin-resistant women and fall with weight loss. J Clin Endocrinol Metab 2006; 91(5): 1896–900.
Erdoğmuş F, Koca C, Selçoki Y, Karakurt F, Aydın M, Çarlıoğlu A, Eryonucu B, Yiğitoğlu R. Metabolik Sendromda Endotel Disfonksiyonu ve Ateroskleroz Riski Arasındaki İlişkinin Oksidatif Stres Üzerinden Değerlendirilmesi. Turkiye Klinikleri J Cardiovasc Sci 2009; 21(1).
Engin AB. Adipocyte-Macrophage Cross-Talk in Obesity. Adv Exp Med Biol 2017; 960: 327–43.
Mangge H, Freytag F, Almer G, Weghuber D, BauerDenk C, Fuchs D. Serum neopterin is not increased in obese juveniles. J Obes 2011; 2011: 946795.
Ursavaş A, Karadag M, Oral AY, Demirdogen E, Oral HB, Ege E. Association between serum neopterin, obesity and daytime sleepiness in patients with obstructive sleep apnea. Respir Med 2008; 102(8): 1193–7.
Kabaroğlu C, Ersoy B, Onur E, Özhan B, Erdin S, Var A, Bayındır O, Dinç G. Elevated glucose level at 30 minutes during an oral glucose tolerance test in obese adolescents: a new disorder of glucose tolerance. Endocr J 2013; 60(2): 197–205.
Agacayak E, Tunc SY, Sak S, Basaranoglu S, Yüksel H, Turgut A, Gul T. Levels of neopterin and other inflammatory markers in obese and non-obese patients with polycystic ovary syndrome. Med Sci Monit 2015; 21: 2446–55.
Bekçi TT, Kesli R, Koçak N. Serum Neopterin Levels in Obese and Nonobese Patients with Obstructive Sleep Apnea Syndrome. Journal of Inonu University Faculty of Medicine 2010; 17(3): 165–8.
Yuniatry D, Santoso A, Atif M. Correlation of neopterin and TNF-α with asymmetric dimethylarginine in metabolic syndrome. Indones Biomed J 2011; 3(3): 200–3.
Huang F, del-Río-Navarro BE, Pérez Ontiveros JA, RuizBedolla E, Navarro-Olivos E, Villafaña S, Bravo G, Hong E. Changes in ghrelin and asymmetrical dimethylarginine in obese Mexican adolescents after six-month lifestyle intervention. Endocrine 2013; 43(3): 603–10.
Eid HM, Arnesen H, Hjerkinn EM, Lyberg T, Seljeflot I. Relationship between obesity, smoking, and the endogenous nitric oxide synthase inhibitor, asymmetric dimethylarginine. Metabolism 2004; 53(12): 1574–9.
Kocak H, Oner-Iyidogan Y, Gurdol F, Oner P, Esin D. Serum Asymmetric Dimethylarginine and Nitric Oxide Levels in Obese Postmenopausal Women. J Clin Lab Anal 2011; 25(3): 174–8.
Eberhard, R.2007. Total Cardiovascular Risk Management. Am J Cardiol 100, 53–60.
Hajar Rachel. Framing Contribution to Cardiovascular Disease. Heart Views 2016; 17 (2): 78–81.
Copyright (c) 2020 Emre Avci, Alpaslan Karabulut, Gulcin Alp Avci, Burcu Baba, Cumhur Bilgi
This work is licensed under a Creative Commons Attribution 4.0 International License.
The published articles will be distributed under the Creative Commons Attribution 4.0 International License (CC BY). It is allowed to copy and redistribute the material in any medium or format, and remix, transform, and build upon it for any purpose, even commercially, as long as appropriate credit is given to the original author(s), a link to the license is provided and it is indicated if changes were made. Users are required to provide full bibliographic description of the original publication (authors, article title, journal title, volume, issue, pages), as well as its DOI code. In electronic publishing, users are also required to link the content with both the original article published in Journal of Medical Biochemistry and the licence used.
Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.