Neurotrimin and Syndecan-1 Biomarker Levels in Patients With Decompensated Heart Failure

Document Type : Original Article


1 Department of Emergency Medicine, Imam Khomeini Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IR Iran.

2 Department of Emergency Medicine, Golestan Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IR Iran.

3 Department of Pathology, School of Medicine, Ahvaz Jundishapur University of Medical sciences, Ahvaz, IR Iran.

4 Department of Emergency Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IR Iran.


Background: Heart failure (HF) is a complex clinical syndrome estimated to have afflicted 23 million people worldwide. This study aimed to measure syndecan-1 and neurotrimin levels in patients with decompensated heart failure (DHF) admitted to the emergency department.
Methods: This study was conducted from November 2017 through June 2018 in Imam Khomeini Hospital, a referral center in Ahvaz, Iran. Baseline demographics were recorded. The Human Syndecan-1/CD138 (SDC1) ELISA kit for the measurement of syndecan 1 and the Human Neurotrimin ELISA kit for the measurement of neurotrimin (ZellBio GmbH, Berlin, Germany) were used. The detection range for syndecan 1 and neurotrimin was 1.5 to 48 ng/mL and 0.4 to 12.8 ng/mL, respectively.
Results: Seventy-two patients met the study inclusion criteria. The mean level of syndecan 1 and neurotrimin was 24.31 ± 8.27 ng/mL (11–37 ng/mL) and 0.52 ± 0.19 ng/mL (0–9 ng/mL), respectively. The results showed no correlations between the severity of illness and syndecan-1 and neurotrimin levels, nor were there any correlations between age, sex, blood urea nitrogen, creatinine, the estimated glomerular filtration rate, and B-type natriuretic peptide (in DHF >500 ng/mL) and the levels of syndecan 1 and neurotrimin (P >0.05).
Conclusions: The syndecan-1 level did not change in patients suffering from HF with reduced ejection fraction (EF). Further, patients in any EF classification had a low level of neurotrimin. However, no significant associations were found between the classes of the EF and the serum neurotrimin level. (Iranian Heart Journal 2021; 22(3): 88-94)


  1. Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, De Ferranti S, Després J-P, Fullerton HJ, Howard VJ: Executive summary: heart disease and stroke statistics—2015 update: a report from the American Heart Association. circulation 2015, 131(4):434-441.
  2. Nieminen MS, Brutsaert D, Dickstein K, Drexler H, Follath F, Harjola V-P, Hochadel M, Komajda M, Lassus J, Lopez-Sendon JL: EuroHeart Failure Survey II (EHFS II): a survey on hospitalized acute heart failure patients: description of population. European heart journal 2006, 27(22):2725-2736.
  3. Fonarow GC, Abraham WT, Albert NM, Gattis Stough W, Gheorghiade M, Greenberg BH, O’Connor CM, Nunez E, Yancy CW, Young JB: Day of admission and clinical outcomes for patients hospitalized for heart failure: findings from the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients With Heart Failure (OPTIMIZE-HF). Circulation: Heart Failure 2008, 1(1):50-57.
  4. Clerico A, Vittorini S, Passino C, Emdin M: New and emerging biomarkers of heart failure. Critical reviews in clinical laboratory sciences 2009, 46(3):107-128.
  5. van Kimmenade RR, Januzzi Jr JL: Emerging biomarkers in heart failure. Clinical chemistry 2012, 58(1):127-138.
  6. Meijers W, Van der Velde A, De Boer R: Biomarkers in heart failure with preserved ejection fraction. Netherlands Heart Journal 2016, 24(4):252-258.
  7. Alexander CM, Reichsman F, Hinkes MT, Lincecum J, Becker KA, Cumberledge S, Bernfield M: Syndecan-1 is required for Wnt-1-induced mammary tumorigenesis in mice. Nature genetics 2000, 25(3):329-332.
  8. Vanhoutte D, Schellings M, Stepp M, Carmeliet P, Van de Werf F, Heymans S: 522 Increased expression of syndecan‐1 protects against cardiac dilatation and dysfunction after myocardial infarction. European Journal of Heart Failure Supplements 2006, 5:111-111.
  9. de Oliveira Neves FM, Meneses GC, Sousa NEA, Parahyba MC, Martins AMC, Libório AB: Syndecan-1 in Acute Decompensated Heart Failure–Association With Renal Function and Mortality–. Circulation Journal 2015, 79(7):1511-1519.
  10. Tromp J, van der Pol A, Klip IT, de Boer RA, Jaarsma T, van Gilst WH, Voors AA, van Veldhuisen DJ, van der Meer P: Fibrosis marker syndecan-1 and outcome in patients with heart failure with reduced and preserved ejection fraction. Circulation: Heart Failure 2014, 7(3):457-462.
  11. Chen S, Gil O, Ren YQ, Zanazzi G, Salzer JL, Hillman DE: Neurotrimin expression during cerebellar development suggests roles in axon fasciculation and synaptogenesis. Journal of neurocytology 2001, 30(11):927-937.
  12. Cao TH, Quinn PA, Sandhu JK, Voors AA, Lang CC, Parry HM, Mohan M, Jones DJ, Ng LL: Identification of novel biomarkers in plasma for prediction of treatment response in patients with heart failure. The Lancet 2015, 385:S26.
  13. van Veldhuisen DJ, Linssen GC, Jaarsma T, van Gilst WH, Hoes AW, Tijssen JG, Paulus WJ, Voors AA, Hillege HL: B-type natriuretic peptide and prognosis in heart failure patients with preserved and reduced ejection fraction. Journal of the American College of Cardiology 2013, 61(14):1498-1506.
  14. Wang YY, Zhong JH, Su ZY, Huang JF, Lu SD, Xiang BD, Ma L, Qi LN, Ou BN, Li LQ: Albumin–bilirubin versus Child–Pugh score as a predictor of outcome after liver resection for hepatocellular carcinoma. British Journal of Surgery 2016, 103(6):725-734.
  15. Bennett JA, Riegel B, Bittner V, Nichols J: Validity and reliability of the NYHA classes for measuring research outcomes in patients with cardiac disease. Heart & Lung 2002, 31(4):262-270.
  16. Tromp J, Khan MA, Mentz RJ, O’Connor CM, Metra M, Dittrich HC, Ponikowski P, Teerlink JR, Cotter G, Davison B: Biomarker profiles of acute heart failure patients with a mid-range ejection fraction. JACC: Heart Failure 2017, 5(7):507-517.
  17. Frangogiannis NG: Syndecan-1: a critical mediator in cardiac fibrosis. In.: Am Heart Assoc; 2010.
  18. Schellings MW, Vanhoutte D, Götte M, Swinnen M, Herias V, Wild MK, Vestweber D, Chorianopoulos E, Cortés V, Rigotti A: Increased expression of Syndecan-1 protects against cardiac dilatation and dysfunction after acute myocardial infarction. Matricellular proteins 2007, 115(4):55.
  19. Lei J, Xue SN, Wu W, Zhou SX, Zhang YL, Yuan GY, Wang JF: Increased level of soluble syndecan-1 in serum correlates with myocardial expression in a rat model of myocardial infarction. Molecular and cellular biochemistry 2012, 359(1-2):177-182.
  20. Krizsan‐Agbas D, Pedchenko T, Smith PG: Neurotrimin is an estrogen‐regulated determinant of peripheral sympathetic innervation. Journal of neuroscience research 2008, 86(14):3086-3095.
  21. Sugimoto C, Maekawa S, Miyata S: OBCAM, an immunoglobulin superfamily cell adhesion molecule, regulates morphology and proliferation of cerebral astrocytes. Journal of neurochemistry 2010, 112(3):818-828.
  22. Akeel M, McNamee CJ, Youssef S, Moss D: DIgLONs inhibit initiation of neurite outgrowth from forebrain neurons via an IgLON-containing receptor complex. Brain research 2011, 1374:27-35.
  23. Ye M, Parente F, Li X, Perryman MB, Zelante L, Wynshaw‐Boris A, Chen J, Grossfeld P: Gene‐targeted deletion of OPCML and Neurotrimin in mice does not yield congenital heart defects. American Journal of Medical Genetics Part A 2014, 164(4):966-974.
  24. Sellar GC, Watt KP, Rabiasz GJ, Stronach EA, Li L, Miller EP, Massie CE, Miller J, Contreras-Moreira B, Scott D: OPCML at 11q25 is epigenetically inactivated and has tumor-suppressor function in epithelial ovarian cancer. Nature genetics 2003, 34(3):337-343.
  25. Ntougkos E, Rush R, Scott D, Frankenberg T, Gabra H, Smyth JF, Sellar GC: The IgLON family in epithelial ovarian cancer: expression profiles and clinicopathologic correlates. Clinical cancer research 2005, 11(16):5764-5768.
  26. Cui Y, Ying Y, Van Hasselt A, Ng KM, Yu J, Zhang Q, Jin J, Liu D, Rhim JS, Rha SY: OPCML is a broad tumor suppressor for multiple carcinomas and lymphomas with frequently epigenetic inactivation. PloS one 2008, 3(8).
  27. McKie AB, Vaughan S, Zanini E, Okon IS, Louis L, de Sousa C, Greene MI, Wang Q, Agarwal R, Shaposhnikov D: The OPCML tumor suppressor functions as a cell surface repressor–adaptor, negatively regulating receptor tyrosine kinases in epithelial ovarian cancer. Cancer discovery 2012, 2(2):156-171.