Vol 24, No 3 (2020)
Original paper
Published online: 2020-09-16

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Serum amphiregulin and cerebellin 1 levels in primary hypertension patients

Özlem Güler1, Hakan Hakkoymaz1, Sedat Köroğlu2, Muhammed Seyithanoğlu3, Hakan Güneş4
Arterial Hypertension 2020;24(3):120-127.


Background: Hypertension is a major risk factor for cardiovascular diseases, stroke, congestive heart disease and renal failure. Primary hypertension is a multi-factorial complex disease and its exact etiology still remains unknown. In this study we aimed to compare serum amphiregulin and cerebellin-1 levels of primary hypertension patients with healthy subjects.

Material and methods: Forty-four hypertensive patients and 44 healthy people were included. Patients with systolic blood pressure measurements ≥ 140 mm Hg and diastolic blood pressure measurements ≥ 90 mm Hg were evaluated as hypertensive. Serum amphiregulin and cerebellin 1 levels were measured using ELISA method.

Results: Mean amphiregulin level was 32.1 (10.2–72.5) pg/mL in hypertension group and 36.9 (15.9–109.5) pg/mL in control group (p = 0.002). Mean cerebellin 1 levels were comparable in both groups, 82.1 (23.9–286.1) pg/mL in hypertensive group and 95.1 (60.2–293) pg/mL in control group (p = 0.261). Serum amphiregulin to predict hypertension was found to be ≤ 23 pg/mL with specificity of 97% and sensitivity of 48.5% (AUC = 0.74; 95% CI, 0.62–0.86; p = 0.001).

Conclusions: Hypertension is associated with lower serum amphiregulin concentrations.

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  1. Lawes C, Hoorn S, Rodgers A. Global burden of blood-pressure-related disease, 2001. Lancet. 2008; 371(9623): 1513–1518.
  2. Singh M, Singh AK, Pandey P, et al. Molecular genetics of essential hypertension. Clin Exp Hypertens. 2016; 38(3): 268–277.
  3. Pierdomenico SD, Di Nicola M, Esposito AL, et al. Prognostic value of different indices of blood pressure variability in hypertensive patients. Am J Hypertens. 2009; 22(8): 842–847.
  4. Staruschenko A, Palygin O, Ilatovskaya DV, et al. Epidermal growth factors in the kidney and relationship to hypertension. Am J Physiol Renal Physiol. 2013; 305(1): F12–F20.
  5. Schreier B, Gekle M, Grossmann C. Role of epidermal growth factor receptor in vascular structure and function. Curr Opin Nephrol Hypertens. 2014; 23(2): 113–121.
  6. Makki N, Thiel KW, Miller FJ. The epidermal growth factor receptor and its ligands in cardiovascular disease. Int J Mol Sci. 2013; 14(10): 20597–20613.
  7. Berasain C, Avila MA. Amphiregulin. Semin Cell Dev Biol. 2014; 28: 31–41.
  8. Seigneur E, Südhof TC. Cerebellins are differentially expressed in selective subsets of neurons throughout the brain. J Comp Neurol. 2017; 525(15): 3286–3311.
  9. Mazzocchi G, Andreis PG, De Caro R, et al. Cerebellin enhances in vitro secretory activity of human adrenal gland. J Clin Endocrinol Metab. 1999; 84(2): 632–635.
  10. Rucinski M, Ziolkowska A, Szyszka M, et al. Precerebellin-related genes and precerebellin 1 peptide in endocrine glands of the rat - pattern of their expression. Int J Mol Med. 2009; 23(1): 113–119.
  11. Strowski MZ, Kaczmarek P, Mergler S, et al. Insulinostatic activity of cerebellin--evidence from in vivo and in vitro studies in rats. Regul Pept. 2009; 157(1-3): 19–24.
  12. Satoh F, Takahashi K, Murakami O, et al. Cerebellin and cerebellin mRNA in the human brain, adrenal glands and the tumour tissues of adrenal tumour, ganglioneuroblastoma and neuroblastoma. J Endocrinol. 1997; 154(1): 27–34.
  13. Aydin S. Can cerebellin and renalase measurements contribute to the elimination of false positive results in pheochromocytoma and paraganglioma diagnoses? Med Hypotheses. 2017; 107: 64.
  14. Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2018; 138(17): e484–e594.
  15. McCormack T, Boffa RJ, Jones NR, et al. The 2018 ESC/ESH hypertension guideline and the 2019 NICE hypertension guideline, how and why they differ. Eur Heart J. 2019; 40(42): 3456–3458.
  16. Güneş H, Alkan Baylan F, Güneş H, et al. Can Nesfatin-1 Predict Hypertension in Obese Children? J Clin Res Pediatr Endocrinol. 2020; 12(1): 29–36.
  17. Temiz F, Güneş H, Güneş H. Evaluation of Atrial Electromechanical Delay in Children with Obesity. Medicina (Kaunas). 2019; 55(6).
  18. Schreier B, Rabe S, Schneider B, et al. Loss of epidermal growth factor receptor in vascular smooth muscle cells and cardiomyocytes causes arterial hypotension and cardiac hypertrophy. Hypertension. 2013; 61(2): 333–340.
  19. Fernandez-Patron C. Therapeutic potential of the epidermal growth factor receptor transactivation in hypertension: a convergent signaling pathway of vascular tone, oxidative stress, and hypertrophic growth downstream of vasoactive G-protein-coupled receptors? Can J Physiol Pharmacol. 2007; 85(1): 97–104.
  20. Lundstam U, Hägg U, Sverrisdottir YB, et al. Epidermal growth factor levels are related to diastolic blood pressure and carotid artery stiffness. Scand Cardiovasc J. 2007; 41(5): 308–312.
  21. Takayanagi T, Kawai T, Forrester SJ, et al. Role of epidermal growth factor receptor and endoplasmic reticulum stress in vascular remodeling induced by angiotensin II. Hypertension. 2015; 65(6): 1349–1355.
  22. Zeng F, Singh AB, Harris RC. The role of the EGF family of ligands and receptors in renal development, physiology and pathophysiology. Exp Cell Res. 2009; 315(4): 602–610.
  23. Pavlov TS, Levchenko V, O'Connor PM, et al. Deficiency of renal cortical EGF increases ENaC activity and contributes to salt-sensitive hypertension. J Am Soc Nephrol. 2013; 24(7): 1053–1062.
  24. Bauer JH, Reams GP, Wu Z. The aging hypertensive kidney: pathophysiology and therapeutic options. Am J Med. 1991; 90(4B): 21S–27S.
  25. Schwartz GL, Strong CG. Renal parenchymal involvement in essential hypertension. Med Clin North Am. 1987; 71(5): 843–858.
  26. Giaconi S, Levanti C, Fommei E, et al. Microalbuminuria and casual and ambulatory blood pressure monitoring in normotensives and in patients with borderline and mild essential hypertension. Am J Hypertens. 1989; 2(4): 259–261.
  27. Ateş K, Ertuğ E, Arıcan A, et al. Microproteinuria and Serum Uric Acid Levels as Early Markers of Renal Involvement in Essential Hypertension. Ankara Tıp Mecmuası (J Faculty Med). 1994; 47: 433–446.
  28. Rucinski M, Ziolkowska A, Szyszka M, et al. Cerebellin and des-cerebellin exert ACTH-like effects on corticosterone secretion and the intracellular signaling pathway gene expression in cultured rat adrenocortical cells--DNA microarray and QPCR studies. Int J Mol Med. 2009; 23(4): 539–546.
  29. Albertin G, Malendowicz LK, Macchi C, et al. Cerebellin stimulates the secretory activity of the rat adrenal gland: in vitro and in vivo studies. Neuropeptides. 2000; 34(1): 7–11.
  30. Hochól A, Neri G, Majchrzak M, et al. Prolonged cerebellin administration inhibits the growth, but enhances steroidogenic capacity of rat adrenal cortex. Endocr Res. 2001; 27(1-2): 11–17.
  31. Gouli A, Kaltsas G, Tzonou A, et al. High prevalence of autonomous aldosterone secretion among patients with essential hypertension. Eur J Clin Invest. 2011; 41(11): 1227–1236.
  32. Güler Ö, Özer A, Seyithanoğlu M, et al. Serum amphiregulin and cerebellin-1 levels in severe preeclampsia. J Matern Fetal Neonatal Med. 2019 [Epub ahead of print]: 1–6.