Skip to content
Licensed Unlicensed Requires Authentication Published by De Gruyter July 30, 2016

Low concentrations of adropin are associated with endothelial dysfunction as assessed by flow-mediated dilatation in patients with metabolic syndrome

  • Coskun U. Oruc , Yunus E. Akpinar , Elmire Dervisoglu , Shirkhan Amikishiyev , Artur Salmaslıoglu , Figen Gurdol EMAIL logo and Beyhan Omer

Abstract

Background:

In individuals with atherosclerotic risk factors, endothelial dysfunction (ED) appears as an early phase in the development of clinical symptoms. Recent studies indicate that adropin, a newly identified peptide, participates in cardiovascular health through the regulation of several metabolic events including angiogenesis and blood flow. In this study, we aimed to determine the relation of adropin with biochemical and radiologic parameters which reflect ED such as endothelial nitric oxide synthase (eNOS), endothelin 1 (ET-1), nitric oxide (NO) and flow-mediated dilatation (FMD) along with the routine biochemical measurements in patients recently diagnosed with metabolic syndrome (MetS).

Methods:

Fasting blood samples from 110 patients with MetS diagnosed according to the NCEP ATP III-2005 criteria were collected to measure the concentrations of adropin and other parameters including the lipid profile, insulin and glucose. Serum NOx concentrations were determined by measuring NO2 plus NO3. FMD test was performed by ultrasonography, and patients were stratified as FMD (+) or (–). Data were compared between these two subgroups and also with matching healthy controls (n=50). Biochemical data were evaluated using Student’s t or Mann-Whitney U tests.

Results:

Fifty-nine subjects had ED (+) and the remaining 101 subjects were ED (–). In the first group, adropin levels were significantly lower than the latter (2.13±1.05 vs. 3.41±1.63 ng/mL, respectively; p<0.001) and independently associated with FMD positivity as assessed by the logistic regression analysis.

Conclusions:

Low adropin level in circulation is related to ED and has a close association with FMD. Any alterations in its level may be of help in order to assess the development of ED before the occurrence of clinical symptoms in patients with metabolic syndrome.

Acknowledgments

This study was supported by the Research Fund of Istanbul University, project no. t-44085.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

1. Kumar KG, Trevaskis JL, Lam DD, Sutton GM, Koza RA, Chouljenko VN, et al. Identification of adropin as a secreted factor linking dietary macronutrient intake with energy homeostasis and lipid metabolism. Cell Metab 2008;8:468–81.10.1016/j.cmet.2008.10.011Search in Google Scholar PubMed PubMed Central

2. Celik A, Balin M, Kobat MA, Erdem K, Baydas A, Bulut M, et al. Deficiency of a new protein associated with cardiac syndrome X; called adropin. Cardiovasc Ther 2013;3:174–8.10.1111/1755-5922.12025Search in Google Scholar PubMed

3. Gao S, McMillan RP, Zhu Q, Lopaschuk GD, Hulver MW, Butler AA. Therapeutic effects of adropin on glucose tolerance and substrate utilization in diet-induced obese mice with insulin resistance. Mol Metab 2015;4:310–24.10.1016/j.molmet.2015.01.005Search in Google Scholar PubMed PubMed Central

4. Lovren F, Pan Y, Quan A, Singh KK, Shukla PC, Gupta M, et al. Adropin is a novel regulator of endothelial function. Circulation 2010;122:S185–92.10.1161/CIRCULATIONAHA.109.931782Search in Google Scholar PubMed

5. Kumar KG, Zhang J, Gao S, Rossi J, McGuinness OP, Halem HH, et al. Adropin deficiency is associated with increased adiposity and insulin resistance. Obesity 2012;20:1394–402.10.1038/oby.2012.31Search in Google Scholar PubMed PubMed Central

6. Topuz M, Celik A, Aslantas T, Demir AK, Aydin S, Aydin S. Plasma adropin levels predict endothelial dysfunction like flow-mediated dilatation in patients with type 2 diabetes mellitus. J Invest Med 2013;61:1161–4.10.2310/JIM.0000000000000003Search in Google Scholar PubMed

7. Yu HY, Zhao P, Wu MC, Liu J, Yin W. Serum adropin levels are decreased in patients with acute myocardial infarction. Regul Pept 2014;190–191:46–9.10.1016/j.regpep.2014.04.001Search in Google Scholar PubMed

8. Gu X, Li H, Zhu X, Gu H, Chen J, Wang L, et al. Inverse correlation between plasma adropin and et-1 levels in essential hypertension: a cross-sectional study. Medicine (Baltimore) 2015;94:e1712.10.1097/MD.0000000000001712Search in Google Scholar PubMed PubMed Central

9. Castellon X, Bogdanova V. Chronic inflammatory diseases and endothelial dysfunction. Aging Dis 2016;7:81–9.10.14336/AD.2015.0803Search in Google Scholar PubMed PubMed Central

10. Davis MJ, Hill MA. Signaling mechanisms underlying the vascular myogenic response. Physiol Rev 1999;79:387–423.10.1152/physrev.1999.79.2.387Search in Google Scholar PubMed

11. Coretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F, Creager MA, et al. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the international brachial artery reactivity task force. J Am Coll Cardiol 2002;39:257–65.10.1016/S0735-1097(01)01746-6Search in Google Scholar

12. Lüscher TF, Barton M. Endothelins and endothelin receptor antagonists: therapeutic considerations for a novel class of cardiovascular drugs. Circulation 2000;102:2434–40.10.1161/01.CIR.102.19.2434Search in Google Scholar

13. Ahirwar AK, Jain A, Singh A, Goswami B, Bhatnagar MK, Bhatacharjee J. The study of markers of endothelial dysfunction in metabolic syndrome. Horm Mol Biol Clin Invest 2015;24:131–6.10.1515/hmbci-2015-0039Search in Google Scholar PubMed

14. Guden DS, Tunctan B. The role of endothelin-1 in the pathogenesis of diabetes. MÜSBED 2014;4:158–67.10.5455/musbed.20140723023147Search in Google Scholar

15. Song R, Chou YI, Kong J, Li J, Pan B, Cui M, et al. Association of endothelial microparticle with NO, eNOS, ET-1, and fractional flow reserve in patients with coronary intermediate lesions. Biomarkers 2015;20:429–35.10.3109/1354750X.2015.1094140Search in Google Scholar PubMed

16. Blaise GA, Gauvin D, Gangal M, Authier S. Nitric oxide, cell signaling and cell death. Toxicology 2005;208:177–92.10.1016/j.tox.2004.11.032Search in Google Scholar PubMed

17. Sukhovershin RA, Yepuri G, Ghebremariam YT. Endothelium-derived nitric oxide as an antiatherogenic mechanism: implications for therapy. Methodist Debakey Cardiovasc J 2015;11:166–71.10.14797/mdcj-11-3-166Search in Google Scholar PubMed PubMed Central

18. Sun YX, Hu SJ, Zhang XH, Sun J, Zhu CH, Zhang ZJ. [Plasma levels of vWF and NO in patients with metabolic syndrome and their relationship with metabolic disorders]. Zhejiang Da Xue Bao Yi Xue Ban 2006;35:315–8.Search in Google Scholar

19. Cengiz M, Yavuzer S, Kılıçkıran Avcı B, Yürüyen M, Yavuzer H, Dikici SA, et al. Circulating miR-21 and eNOS in subclinical atherosclerosis in patients with hypertension. Clin Exp Hypertens 2015;37:643–9.10.3109/10641963.2015.1036064Search in Google Scholar PubMed

20. Bucala R, Tracey KJ, Cerami A. Advanced glycosylation products quench nitric oxide and mediate defective endothelium-dependent vasodilatation in experimental diabetes. J Clin Invest 1991;87:432–8.10.1172/JCI115014Search in Google Scholar PubMed PubMed Central

21. Pannirselvam M, Verma S, Anderson TJ, Triggle CR. Cellular basis of endothelial dysfunction in small mesenteric arteries from spontaneously diabetic (db/db -/-) mice: role of decreased tetrahydrobiopterin bioavailability. Br J Pharmacol 2002;136:255–63.10.1038/sj.bjp.0704683Search in Google Scholar PubMed PubMed Central

22. Pieper GM. Review of alterations in endothelial nitric oxide production in diabetes: protective role of arginine on endothelial dysfunction. Hypertension 1998;31:1047–60.10.1161/01.HYP.31.5.1047Search in Google Scholar PubMed

23. Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute scientific statement: executive summary. Crit Pathw Cardiol 2005;4:198–203.10.1097/00132577-200512000-00018Search in Google Scholar PubMed

24. Wu L, Fang J, Chen L, Zhao Z, Luo Y, Lin C, et al. Low serum adropin is associated with coronary atherosclerosis in type 2 diabetic and non-diabetic patients. Clin Chem Lab Med 2014;52:751–8.10.1515/cclm-2013-0844Search in Google Scholar PubMed

25. Alley H, Owens CD, Gasper WJ, Grenon SM. Ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery in clinical research. J Vis Exp 2014;92:e52070.10.3791/52070Search in Google Scholar PubMed PubMed Central

26. Förstermann U, Sessa WC. Nitric oxide synthases: regulation and function. Eur Heart J 2012;33:829–37.10.1093/eurheartj/ehr304Search in Google Scholar PubMed PubMed Central

27. Lauer T, Preik M, Rassaf T, Strauer BE, Deussen A, Feelisch M, et al. Plasma nitrite rather than nitrate reflects regional endothelial nitric oxide synthase activity but lacks intrinsic vasodilator action. Proc Natl Acad Sci USA 2001;98:12814–9.10.1073/pnas.221381098Search in Google Scholar PubMed PubMed Central

28. Pernow J, Shemyakin A, Böhm F. New perspectives on endothelin-1 in atherosclerosis and diabetes mellitus. Life Sci 2012;91:507–16.10.1016/j.lfs.2012.03.029Search in Google Scholar PubMed

Received: 2016-4-21
Accepted: 2016-6-20
Published Online: 2016-7-30
Published in Print: 2017-1-1

©2017 Walter de Gruyter GmbH, Berlin/Boston

Downloaded on 28.3.2024 from https://www.degruyter.com/document/doi/10.1515/cclm-2016-0329/html
Scroll to top button