Phoenixin plasma concentration in heart failure with reduced ejection fraction patients
More details
Hide details
Anesthesiology, Intensive Care and Emergency Medicine Department, Collegium Medicum, University of Zielona Gora, Poland
Research and Development Center, Regional Specialist Hospital, Wroclaw, Poland
Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland
1st Department of Cardiology, Poznan University of Medical Sciences, Poland
Tomasz Zemleduch   

Anesthesiology, Intensive Care and Emergency Medicine Department, Collegium Medicum, University of Zielona Gora, Zyty 28, 65-046 Zielona Góra, Poland. Tel.: +48 607 162 333.
Submission date: 2022-03-08
Final revision date: 2022-05-30
Acceptance date: 2022-05-30
Online publication date: 2022-10-05
Heart failure (HF) nowadays in western countries is an immense problem largely due to its social impact as well as an economic burden. A widely accepted biomarker-based strategy to establish prognosis and predict re-hospitalization events in HF is lacking. Currently, besides natriuretic peptides and cardiac troponins, a variety of molecules are being studied. Phoenixin (PNX) is a neuropeptide mainly involved in the regulation of gonadotropin secretion. Recently, a significant cardioprotective effect of PNX was reported.

The aim of this study was to measure PNX plasma concentration in a group of HF with reduced ejection fraction (HFrEF) patients and to compare it to levels found in HF-negative participants.

Material and methods:
A group of 74 HFrEF patients and a control group consisting of 40 participants without systolic or diastolic myocardial dysfunction were studied. Each individual underwent anthropometric measurements, laboratory testing, clinical and echocardiographic examination. To evaluate PNX plasma concentration, an immunoenzymatic assay (ELISA) was performed.

Results and discussion:
PNX plasma concentration in the HFrEF group was not statistically different than in the control group. No significant correlation between PNX level and age, sex, BMI, HF etiology, diabetes or atrial fibrillation presence was found. PNX concentration correlated positively with total and LDL cholesterol blood levels in HFrEF patients. A negative correlation was found with creatinine in HFrEF, uric acid and triglycerides levels as well as AlAT activity in the control group.

There is no significant difference in PNX plasma concentration between HF and non-HF individuals. PNX role in cardiovascular disease requires further investigation.

Project supported by Wroclaw Centre of Biotechnology, The Leading National Research Centre (KNOW) programme for years 2014–2018, no. W1/1/4/2018.
None declared.
Polish Central Statistical Office: Accessed: 16.09.2022.
Nessler J, Kozierkiewicz A, Gackowski A, et al. Coordinated heart failure care in Poland: towards optimal organisation of the health care system [in Polish]. Kardiol Pol. 2018;76(2):479–487.
Benjamin EJ, Muntner P, Alonso A, et al. Heart disease and stroke statistics – 2019 update: A report from the American Heart Association. Circulation. 2019;139(10): 56–528.
Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. The Lancet. 2020;395(10229):1054–1062.
Deng Q, Hu B, Zhang Y, et al. Suspected myocardial injury in patients with COVID-19: Evidence from front-line clinical observation in Wuhan, China. Int J Cardiol. 2020;311:116–121.
Guo T, Fan Y, Chen M, et al. Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19). JAMA Cardiol. 2020;5(7):811–818.
Lorente-Ros A, Monteagudo Ruiz JM, Rincón LM, et al. Myocardial injury determination improves risk stratification and predicts mortality in COVID-19 patients. Cardiol J. 2020;27(5):489–496.
Puntmann VO, Ludovica Carerj M, Wieters I, et al. Outcomes of cardiovascular magnetic resonance imaging in patients recently recovered from coronavirus disease 2019 (COVID-19). JAMA Cardiol. 2020;5(11):1265–1273.
McDonagh TA, Metra M, Adamo M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021;42(36):3599–3726.
Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001;69(3):89–95.
Dobrek L, Thor P. Novel biomarkers of acute kidney injury and chronic kidney disease. Pol Ann Med. 2017;24(1):84–89.
Braunwald E. Biomarkers in heart failure. N Engl J Med. 2008;358(20):2148–2159.
Passino C, Barison A, Vergaro G, et al. Markers of fibrosis, inflammation, and remodeling pathways in heart failure. Clin Chim Acta. 2015;443:29–38.
Savic-Radojevic A, Pljesa-Ercegovac M, Matic M, Simic D, Radovanovic S, Simic T. Novel Biomarkers of Heart Failure. Adv Clin Chem. 2017;79:93–152.
Ibrahim NE, Januzzi JL. Established and emerging roles of biomarkers in heart failure. Circ Res. 2018;123(5):614–629.
Lupón J, de Antonio M, Vila J, et al. Development of a novel heart failure risk tool: the barcelona bio-heart failure risk calculator (BCN bio-HF calculator). PLoS One. 2014;9(1):85466.
Dupuy AM, Curinier C, Kuster N, et al. Multi-Marker Strategy in Heart Failure: Combination of ST2 and CRP Predicts Poor Outcome. PLoS One. 2016;11(6):0157159.
Berezin AE, Kremzer AA, Martovitskaya YV, et al. The utility of biomarker risk prediction score in patients with chronic heart failure. Int J Clin Exp Med. 2015;8(10):18255–18264.
Richter B, Koller L, Hohensinner PJ, et al. A multi-biomarker risk score improves prediction of long-term mortality in patients with advanced heart failure. Int J Cardiol. 2013;168(2):1251–1257.
Yosten GLC, Lyu RM, Hsueh AJW, et al. A novel reproductive peptide, phoenixin. J Neuroendocrinol. 2013;25(2):206–215.
Prinz P, Scharner S, Friedrich T, et al. Central and peripheral expression sites of phoenixin-14 immunoreactivity in rats. Biochem Biophys Res Commun. 2017;493(1):195–201.
Billert M, Rak A, Nowak KW, Skrzypski M. Phoenixin: More than Reproductive Peptide. Int J Mol Sci. 2020;21(21): 8378.
Billert M, Kołodziejski PA, Strowski MZ, Nowak KW, Skrzypski M. Phoenixin-14 stimulates proliferation and insulin secretion in insulin producing INS-1E cells. Biochim Biophys Acta Mol Cell Res. 2019;1866(12):118533.
Billert M, Wojciechowicz T, Jasaszwili M, et al. Phoenixin-14 stimulates differentiation of 3T3-L1 preadipocytes via cAMP/Epac-dependent mechanism. Biochim Biophys Acta Mol Cell Biol Lipids. 2018;1863(12):1449–1457.
Rocca C, Scavello F, Granieri MC, et al. Phoenixin-14: detection and novel physiological implications in cardiac modulation and cardioprotection. Cell Mol Life Sci. 2018;75(4):743–756.
Yuruyen M, Gultekin G, Batun GC, et al. Does plasma phoenixin level associate with cognition? Comparison between subjective memory complaint, mild cognitive impairment, and mild Alzheimer’s disease. Int Psychogeriatr. 2017;29(9):1543–1550.
Ullah K, Ur Rahman T, Wu DD, et al. Phoenixin-14 concentrations are increased in association with luteinizing hormone and nesfatin-1 concentrations in women with polycystic ovary syndrome. Clin Chim Acta. 2017;471:243–247.
Pałasz A, Tyszkiewicz-Nwafor M, Suszka-Świtek A, et al. Longitudinal study on novel neuropeptides phoenixin, spexin and kisspeptin in adolescent inpatients with anorexia nervosa – association with psychiatric symptoms. Nutr Neurosci. 2021;24(11):896–906.
Hofmann T, Weibert E, Ahnis A, et al. Phoenixin is negatively associated with anxiety in obese men. Peptides. 2017;88:32–36.
Mosteller RD. Simplified calculation of body-surface area. N Engl J Med. 1987;317(17):1098.
Devereux RB, Alonso DR, Lutas EM, et al. Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings. Am J Cardiol. 1986;57(6):450–458.
Yuruyen M, Gultekin G, Batun GC, et al. Does plasma phoenixin level associate with cognition? Comparison between subjective memory complaint, mild cognitive impairment, and mild Alzheimer’s disease. Int Psychogeriatr. Published online May 29, 2017:1–8.
Celik F, Aydin S. Blood and aqueous humor phoenixin, endocan and spexin in patients with diabetes mellitus and cataract with and without diabetic retinopathy. Peptides. 2021;150:170728.
Balsam P, Ozierański K, Kapłon-Cieślicka A, et al. Differences in clinical characteristics and 1-year outcomes of hospitalized patients with heart failure in ESC-HF Pilot and ESC-HF-LT registries. Pol Arch Intern Med. 2019;129(2):106–116.
Yao B, Lv J, Du L, Zhang H, Xu Z. Phoenixin-14 protects cardiac damages in a streptozotocin-induced diabetes mice model through SIRT3. Arch Physiol Biochem. 2021:1–9.
Zhang B, Li J. Phoenixin-14 protects human brain vascular endothelial cells against oxygen-glucose deprivation/reoxygenation (OGD/R)-induced inflammation and permeability. Arch Biochem Biophys. 2020;682:108275.
Özkaramanlı Gür D, Sağbaş M, Akyüz A, Güzel S, Alpsoy Ş, Güler N. Role of sympathetic cotransmitter galanin on autonomic balance in heart failure: an active player or a bystander? Anatol J Cardiol. 2017;18(4):281–288.
Pisarenko O, Timotin A, Sidorova M, et al. Cardioprotective properties of N-terminal galanin fragment (2–15) in experimental ischemia/reperfusion injury. Oncotarget. 2017;8(60):101659–101671.
Palkeeva M, Studneva I, Molokoedov A, et al. Galanin/GalR1-3 system: A promising therapeutic target for myocardial ischemia/reperfusion injury. Biomed Pharmacother. 2019;109:1556–1562.