Relationship between Resistin, Endothelin-1, and Flow-Mediated Dilation in Patient with and without Metabolic Syndrome


1 Department of Clinical Biochemistry, Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran

2 Heart Failure Research Center, Cardiovascular Research Institute, Isfahan University of Medical Science, Isfahan, Iran

3 Isfahan Cardiovascular Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran

4 Hypertension Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran


Background: Resistin is peptides that signal the functional status of adipose tissue to the brain and other target organs. It causes insulin resistance and affects the vascular endothelial dysfunction. However, the function and relation between resistin in endothelin-1 (ET-1), which leads to the endothelial dysfunction in humans are enigmatic. Materials and Methods: In a cross-sectional study of 76 participants (38 metabolic syndrome patients and 38 healthy participants), biochemical and clinical parameters, including lipid profile, fasting glucose, resistin, ET-1, C-reactive protein (CRP), flow-mediated dilation (FMD), and hypertension were determined and compared between the two groups. Results: Multiple linear regression analysis was performed with age- and sex-adjusted plasma resistin levels, FMD, and ET-1 as the dependent variables. Analysis showed that weight, body mass index, triglycerides (TGs), and ET-1 were statistically significant correlated with serum resistin. FMD has negative significantly correlated with weight (r = −0.491, P = 0.001), waist circumference (r = −0.491, P = 0.001), waist-to-hip ratio (r = −0.0444, P = 0.001), and ET-1 (r = −0.075, P = 0.050), but it has significantly correlated with systolic blood pressure (SBP) (r = 0.290, P = 0.016), diastolic blood pressure (DBP) (r = 0.275, P = 0.023), and high-density lipoprotein cholesterol (HDL-C) (r = −0.266, P = 0.050), and ET-1, but it has significantly correlated with SBP, DBP, and HDL-C. ET-1 is significantly correlated with TGs (r = −0.436, P = 0.006), total cholesterol (r = 0.452, P = 0.004), low-density lipoprotein cholesterol (r = 0.454, r = 0.004), and resistin (r = 0.282, P = 0.050), whereas it has negative significantly correlated with HDL-C (r = 0.346, P = 0.034), FMD (r = −0.075, P = 0.050. Conclusion: In this study, results shown plasma ET-1 and resistin are suggested as risk factors for the development of endothelial dysfunction and with further study, it is possible that can diagnose the risk of diabetes and cardiovascular disease in the early stages.


Eckel RH, Grundy SM, Zimmet PZ. The metabolic syndrome. Lancet 2005;365:1415-28.  Back to cited text no. 1
Harrabi I, Bouaouina M, Maatoug J, Gaha R, Ghannem H. Prevalence of the metabolic syndrome among urban schoolchildren in Sousse, Tunisia. Int J Cardiol 2009;135:130-1.  Back to cited text no. 2
Espinola-Klein C, Gori T, Blankenberg S, Munzel T. Inflammatory markers and cardiovascular risk in the metabolic syndrome. Front Biosci (Landmark Ed) 2011;16:1663-74.  Back to cited text no. 3
Nikolopoulou A, Kadoglou NP. Obesity and metabolic syndrome as related to cardiovascular disease. Expert Rev Cardiovasc Ther 2012;10:933-9.  Back to cited text no. 4
Shah A, Mehta N, Reilly MP. Adipose inflammation, insulin resistance, and cardiovascular disease. JPEN J Parenter Enteral Nutr 2008;32:638-44.  Back to cited text no. 5
Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, et al. The hormone resistin links obesity to diabetes. Nature 2001;409:307-12.  Back to cited text no. 6
Rak-Mardyła A, Duda M, Gregoraszczuk EŁ. A role for resistin in the ovary during the estrous cycle. Horm Metab Res 2014;46:493-8.  Back to cited text no. 7
Fain JN, Cheema PS, Bahouth SW, Lloyd Hiler M. Resistin release by human adipose tissue explants in primary culture. Biochem Biophys Res Commun 2003;300:674-8.  Back to cited text no. 8
Patel L, Buckels AC, Kinghorn IJ, Murdock PR, Holbrook JD, Plumpton C, et al. Resistin is expressed in human macrophages and directly regulated by PPAR gamma activators. Biochem Biophys Res Commun 2003;300:472-6.  Back to cited text no. 9
McTernan CL, McTernan PG, Harte AL, Levick PL, Barnett AH, Kumar S, et al. Resistin, central obesity, and type 2 diabetes. Lancet 2002;359:46-7.  Back to cited text no. 10
Chen BH, Song Y, Ding EL, Roberts CK, Manson JE, Rifai N, et al. Circulating levels of resistin and risk of type 2 diabetes in men and women: Results from two prospective cohorts. Diabetes Care 2009;32:329-34.  Back to cited text no. 11
Momiyama Y, Ohmori R, Uto-Kondo H, Tanaka N, Kato R, Taniguchi H, et al. Serum resistin levels and cardiovascular events in patients undergoing percutaneous coronary intervention. J Atheroscler Thromb 2011;18:108-14.  Back to cited text no. 12
Ukkola O. Resistin – A mediator of obesity-associated insulin resistance or an innocent bystander? Eur J Endocrinol 2002;147:571-4.  Back to cited text no. 13
Asgary S, SamsamShariat SZ, Ghorbani A, Keshvari M, Sahebkar A, Sarrafzadegan N, et al. Relationship between serum resistin concentrations with metabolic syndrome and its components in an Iranian population. Diabetes Metab Syndr 2015;9:266-70.  Back to cited text no. 14
Lazar MA. Resistin- and obesity-associated metabolic diseases. Horm Metab Res 2007;39:710-6.  Back to cited text no. 15
Yang ZH, Richard V, von Segesser L, Bauer E, Stulz P, Turina M, et al. Threshold concentrations of endothelin-1 potentiate contractions to norepinephrine and serotonin in human arteries. A new mechanism of vasospasm? Circulation 1990;82:188-95.  Back to cited text no. 16
Miyauchi T, Masaki T. Pathophysiology of endothelin in the cardiovascular system. Annu Rev Physiol 1999;61:391-415.  Back to cited text no. 17
Touyz RM, Schiffrin EL. Role of endothelin in human hypertension. Can J Physiol Pharmacol 2003;81:533-41.  Back to cited text no. 18
Weil BR, Westby CM, Van Guilder GP, Greiner JJ, Stauffer BL, DeSouza CA, et al. Enhanced endothelin-1 system activity with overweight and obesity. Am J Physiol Heart Circ Physiol 2011;301:H689-95.  Back to cited text no. 19
Chen C, Jiang J, Lü JM, Chai H, Wang X, Lin PH, et al. Resistin decreases expression of endothelial nitric oxide synthase through oxidative stress in human coronary artery endothelial cells. Am J Physiol Heart Circ Physiol 2010;299:H193-201.  Back to cited text no. 20
Rossi R, Nuzzo A, Origliani G, Modena MG. Prognostic role of flow-mediated dilation and cardiac risk factors in post-menopausal women. J Am Coll Cardiol 2008;51:997-1002.  Back to cited text no. 21
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult treatment panel III). JAMA 2001;285:2486-97.  Back to cited text no. 22
ryar CD, Gu Q, Ogden CL, Flegal KM. Anthropometric Reference Data for Children and Adults: United States, 2011-2014. Vital Health Stat 3. 2016;(39):1-46.  Back to cited text no. 23
Makni E, Moalla W, Benezzeddine-Boussaidi L, Lac G, Tabka Z, Elloumi M, et al. Correlation of resistin with inflammatory and cardiometabolic markers in obese adolescents with and without metabolic syndrome. Obes Facts 2013;6:393-404.  Back to cited text no. 24
Bondonno CP, Yang X, Croft KD, Considine MJ, Ward NC, Rich L, et al. Flavonoid-rich apples and nitrate-rich spinach augment nitric oxide status and improve endothelial function in healthy men and women: A randomized controlled trial. Free Radic Biol Med 2012;52:95-102.  Back to cited text no. 25
Maruhashi T, Soga J, Fujimura N, Idei N, Mikami S, Iwamoto Y, et al. Nitroglycerine-induced vasodilation for assessment of vascular function: A comparison with flow-mediated vasodilation. Arterioscler Thromb Vasc Biol 2013;33:1401-8.  Back to cited text no. 26
Sim JS, Dick JB, Struthers AD. Statin therapy increases vascular sensitivity to angiotensin II in hypercholesterolaemic patients. J Renin Angiotensin Aldosterone Syst 2004;5:109-13.  Back to cited text no. 27
Shahid SM, Nawab SN, Shaikh R, Mahboob T. Glycemic control, dyslipidemia and endothelial dysfunction in coexisted diabetes, hypertension and nephropathy. Pak J Pharm Sci 2012;25:123-9.  Back to cited text no. 28
Eringa EC, Stehouwer CD, van Nieuw Amerongen GP, Ouwehand L, Westerhof N, Sipkema P, et al. Vasoconstrictor effects of insulin in skeletal muscle arterioles are mediated by ERK1/2 activation in endothelium. Am J Physiol Heart Circ Physiol 2004;287:H2043-8.  Back to cited text no. 29
Green DJ, Dawson EA, Groenewoud HM, Jones H, Thijssen DH. Is flow-mediated dilation nitric oxide mediated?: A meta-analysis. Hypertension 2014;63:376-82.  Back to cited text no. 30
Gómez-Ambrosi J, Frühbeck G. Evidence for the involvement of resistin in inflammation and cardiovascular disease. Curr Diabetes Rev 2005;1:227-34.  Back to cited text no. 31
Lin CC, Tsai WC, Chen JY, Li YH, Lin LJ, Chen JH, et al. Supplements of L-arginine attenuate the effects of high-fat meal on endothelial function and oxidative stress. Int J Cardiol 2008;127:337-41.  Back to cited text no. 32
Gudmundsson GS, Sinkey CA, Chenard CA, Stumbo PJ, Haynes WG. Resistance vessel endothelial function in healthy humans during transient postprandial hypertriglyceridemia. Am J Cardiol 2000;85:381-5.  Back to cited text no. 33
Gómez-Guzmán M, Jiménez R, Sánchez M, Zarzuelo MJ, Galindo P, Quintela AM, et al. Epicatechin lowers blood pressure, restores endothelial function, and decreases oxidative stress and endothelin-1 and NADPH oxidase activity in DOCA-salt hypertension. Free Radic Biol Med 2012;52:70-9.  Back to cited text no. 34
Rocha NG, Templeton DL, Greiner JJ, Stauffer BL, DeSouza CA. Metabolic syndrome and endothelin-1 mediated vasoconstrictor tone in overweight/obese adults. Metabolism 2014;63:951-6.  Back to cited text no. 35
Mostafazadeh M, Haiaty S, Rastqar A, Keshvari M. Correlation between resistin level and metabolic syndrome component: A Review. Horm Metab Res 2018;50:521-36.  Back to cited text no. 36
Norata GD, Ongari M, Garlaschelli K, Raselli S, Grigore L, Catapano AL, et al. Plasma resistin levels correlate with determinants of the metabolic syndrome. Eur J Endocrinol 2007;156:279-84.  Back to cited text no. 37
Reilly MP, Lehrke M, Wolfe ML, Rohatgi A, Lazar MA, Rader DJ, et al. Resistin is an inflammatory marker of atherosclerosis in humans. Circulation 2005;111:932-9.  Back to cited text no. 38
de Luis DA, Terroba MC, Cuellar L, Conde R, Primo D, Aller R, et al. Resistin levels in morbid obese patients following the biliopancreatic diversion surgery. Horm Metab Res 2011;43:205-8.  Back to cited text no. 39
Utzschneider KM, Carr DB, Tong J, Wallace TM, Hull RL, Zraika S, et al. Resistin is not associated with insulin sensitivity or the metabolic syndrome in humans. Diabetologia 2005;48:2330-3.  Back to cited text no. 40
Iqbal N, Seshadri P, Stern L, Loh J, Kundu S, Jafar T, et al. Serum resistin is not associated with obesity or insulin resistance in humans. Eur Rev Med Pharmacol Sci 2005;9:161-5.  Back to cited text no. 41
Asano H, Izawa H, Nagata K, Nakatochi M, Kobayashi M, Hirashiki A, et al. Plasma resistin concentration determined by common variants in the resistin gene and associated with metabolic traits in an aged Japanese population. Diabetologia 2010;53:234-46.  Back to cited text no. 42
Osawa H, Tabara Y, Kawamoto R, Ohashi J, Ochi M, Onuma H, et al. Plasma resistin, associated with single nucleotide polymorphism -420, is correlated with insulin resistance, lower HDL cholesterol, and high-sensitivity C-reactive protein in the Japanese general population. Diabetes Care 2007;30:1501-6.  Back to cited text no. 43
Chen CC, Li TC, Li CI, Liu CS, Wang HJ, Lin CC, et al. Serum resistin level among healthy subjects: Relationship to anthropometric and metabolic parameters. Metabolism 2005;54:471-5.  Back to cited text no. 44
Zhang J, Qin Y, Zheng X, Qiu J, Gong L, Mao H, et al. The relationship between human serum resistin level and body fat content, plasma glucose as well as blood pressure. Zhonghua Yi Xue Za Zhi 2002;82:1609-12.  Back to cited text no. 45
Kunnari A, Ukkola O, Päivänsalo M, Kesäniemi YA. High plasma resistin level is associated with enhanced highly sensitive C-reactive protein and leukocytes. J Clin Endocrinol Metab 2006;91:2755-60.  Back to cited text no. 46
Hu WL, Qiao SB, Hou Q, Yuan JS. Plasma resistin is increased in patients with unstable angina. Chin Med J (Engl) 2007;120:871-5.  Back to cited text no. 47