Skip to main content
Top
Published in: BMC Nephrology 1/2018

Open Access 01-12-2018 | Research article

Serum heat shock protein 27 levels predict cardiac mortality in hemodialysis patients

Authors: Andrzej Jaroszyński, Anna Jaroszyńska, Tomasz Zaborowski, Anna Drelich-Zbroja, Tomasz Zapolski, Wojciech Dąbrowski

Published in: BMC Nephrology | Issue 1/2018

Login to get access

Abstract

Background

Decreased heat shock protein 27 (HSP27) participates in many processes that are involved in cardiovascular (CV) disease. The objective of the study was to evaluate if HSP27 level was predictive of mortality as well as to evaluate factors associated with HSP27 level in a group of patients treated with HD.

Methods

Enrolled to the study were 202 HD patients. Clinical data, biochemical, echocardiographic, and carotid atherosclerosis parameters were evaluated. Patients were splited into groups on the basis of the cut-off lower and higher 50th percentile of serum HSP27 levels, and were followed-up for 28.68 ± 6.12 months.

Results

No significant difference was observed between serum HSP27 levels in patients and controls. Low HSP27 patients were older, had higher left ventricular mass index, lower ejection fraction, higher prevalence of diabetes, myocardial infarction and carotid atherosclerosis, higher C-reactive protein level, and worse oxidant/antioxidant status. The multiple regression analysis identified that HSP27 levels were independently, negatively associated with serum oxidized LDL and the number of carotid plaques. Using the Kaplan–Meier analysis it was shown that the cumulative incidences of both CV and sudden cardiac death (SCD) mortality were higher in low HSP27 group in comparison with high serum HSP27 group. A multivariate Cox analysis showed that HSP27 level is an independent and strong predictor of CV as well as SCD mortality.

Conclusions

Low serum HSP27 level is independently associated with both CV and SCD mortality but not with all-cause mortality. Low serum HSP27 level is associated with carotid atherosclerosis and oxidative stress.
Literature
1.
go back to reference Collins A, Foley R, Gilbertson T, Chen S. United States renal data system public health surveillance of chronic kidney disease and end-stage renal disease. Kidney Int Suppl. 2015;5:2–7.CrossRef Collins A, Foley R, Gilbertson T, Chen S. United States renal data system public health surveillance of chronic kidney disease and end-stage renal disease. Kidney Int Suppl. 2015;5:2–7.CrossRef
2.
go back to reference Collins AJ, Kasiske B, Herzog C, et al. Excerpts from the United States renal data system 2006 annual data report. Am J Kidney Dis. 2007;49:1–296.CrossRef Collins AJ, Kasiske B, Herzog C, et al. Excerpts from the United States renal data system 2006 annual data report. Am J Kidney Dis. 2007;49:1–296.CrossRef
3.
go back to reference Vogelzang J, van Stralen K, Noordzij M, et al. Mortality from infections and malignancies in patients treated with renal replacement therapy: data from the ERA-EDTA registry. NephrolDial Transplant. 2015;30:1028–37.CrossRef Vogelzang J, van Stralen K, Noordzij M, et al. Mortality from infections and malignancies in patients treated with renal replacement therapy: data from the ERA-EDTA registry. NephrolDial Transplant. 2015;30:1028–37.CrossRef
4.
go back to reference de Jager D, Grootendorst D, Jager K, et al. Cardiovascular and non cardiovascular mortality among patients starting dialysis. JAMA. 2009;302:1782–9.CrossRef de Jager D, Grootendorst D, Jager K, et al. Cardiovascular and non cardiovascular mortality among patients starting dialysis. JAMA. 2009;302:1782–9.CrossRef
5.
go back to reference Herzog C, Ma J, Collins A. Poor long-term survival after acute myocardial infarction among patients on long-term dialysis. N Engl J Med. 1998;339:799–805.CrossRef Herzog C, Ma J, Collins A. Poor long-term survival after acute myocardial infarction among patients on long-term dialysis. N Engl J Med. 1998;339:799–805.CrossRef
6.
go back to reference Cheung A, Sarnak M, Yan G, et al. HEMO study group. Cardiac diseases in maintenance hemodialysis patients: results of the HEMO study. Kidney Int. 2004;65:2380–90.CrossRef Cheung A, Sarnak M, Yan G, et al. HEMO study group. Cardiac diseases in maintenance hemodialysis patients: results of the HEMO study. Kidney Int. 2004;65:2380–90.CrossRef
7.
go back to reference Di Lullo L, Rivera R, Barbera V, et al. Sudden cardiac death and chronic kidney disease: from pathophysiology to treatment strategies. Int J Cardiol. 2016;217:16–27.CrossRef Di Lullo L, Rivera R, Barbera V, et al. Sudden cardiac death and chronic kidney disease: from pathophysiology to treatment strategies. Int J Cardiol. 2016;217:16–27.CrossRef
8.
go back to reference Poulikakos D, Banerjee D, Malik M. Risk of sudden cardiac death in chronic kidney disease. J Cardiovasc Electrophysiol. 2014;25:222–31.CrossRef Poulikakos D, Banerjee D, Malik M. Risk of sudden cardiac death in chronic kidney disease. J Cardiovasc Electrophysiol. 2014;25:222–31.CrossRef
9.
go back to reference Jaroszyński A, Załuska W, Książek A. Effect of haemodialysis on regional and transmural inhomogeneities of the ventricular repolarisation phase. Nephron Clin Pract. 2005;99:24–30.CrossRef Jaroszyński A, Załuska W, Książek A. Effect of haemodialysis on regional and transmural inhomogeneities of the ventricular repolarisation phase. Nephron Clin Pract. 2005;99:24–30.CrossRef
10.
go back to reference Ritossa F. Discovery of the heat shock response. Cell Stress Chaperones. 1996;1:97–8.CrossRef Ritossa F. Discovery of the heat shock response. Cell Stress Chaperones. 1996;1:97–8.CrossRef
12.
go back to reference Bakthisaran R, Tangirala R, RaoCh M. Small heat shock proteins: Role in cellular functions and pathology. Biochim Biophys Acta. 1854;2015:291–319. Bakthisaran R, Tangirala R, RaoCh M. Small heat shock proteins: Role in cellular functions and pathology. Biochim Biophys Acta. 1854;2015:291–319.
13.
go back to reference Iturbe B, Johnson R. Heat shock proteins and cardiovascular disease. Physiol Int. 2018;105:19–37.CrossRef Iturbe B, Johnson R. Heat shock proteins and cardiovascular disease. Physiol Int. 2018;105:19–37.CrossRef
14.
go back to reference Arrigo A, Virot S, Chaufour S, Firdaus W, Kretz-Remy C, Diaz-Latoud C. Hsp27 consolidates intracellular redox homeostasis by upholding glutathione in its reduced form and by decreasing iron intracellular levels. Antioxid Redox Signal. 2005;7:414–22.CrossRef Arrigo A, Virot S, Chaufour S, Firdaus W, Kretz-Remy C, Diaz-Latoud C. Hsp27 consolidates intracellular redox homeostasis by upholding glutathione in its reduced form and by decreasing iron intracellular levels. Antioxid Redox Signal. 2005;7:414–22.CrossRef
17.
go back to reference Dávila D, Jiménez-Mateos E, Mooney C, Velasco G, Henshall D, Prehn J. Hsp27 binding to the 3’UTR of bim mRNA prevents neuronal death during oxidative stress-induced injury: a novel cytoprotective mechanism. Mol Biol Cell. 2014;25:3413–23.CrossRef Dávila D, Jiménez-Mateos E, Mooney C, Velasco G, Henshall D, Prehn J. Hsp27 binding to the 3’UTR of bim mRNA prevents neuronal death during oxidative stress-induced injury: a novel cytoprotective mechanism. Mol Biol Cell. 2014;25:3413–23.CrossRef
18.
go back to reference Ghayour-Mobarhan M, Saber H, Ferns G. The potential role of heat shock protein 27 in cardiovascular disease. Clin Chim Acta. 2012;413:15–24.CrossRef Ghayour-Mobarhan M, Saber H, Ferns G. The potential role of heat shock protein 27 in cardiovascular disease. Clin Chim Acta. 2012;413:15–24.CrossRef
19.
go back to reference Seibert T, Hibbert B, Chen Y, et al. Serum heat shock protein 27 levels represent a potential therapeutic target for atherosclerosis: observations from a human cohort and treatment of female mice. J Am Coll Cardiol. 2013;62:1446–54.CrossRef Seibert T, Hibbert B, Chen Y, et al. Serum heat shock protein 27 levels represent a potential therapeutic target for atherosclerosis: observations from a human cohort and treatment of female mice. J Am Coll Cardiol. 2013;62:1446–54.CrossRef
20.
go back to reference Hu Y, Yeh H, Tsao H, et al. Electrophysiological correlation and prognostic impact of heat shock protein 27 in atrial fibrillation. Circ Arrhythm Electrophysiol. 2012;5:334–40.CrossRef Hu Y, Yeh H, Tsao H, et al. Electrophysiological correlation and prognostic impact of heat shock protein 27 in atrial fibrillation. Circ Arrhythm Electrophysiol. 2012;5:334–40.CrossRef
21.
go back to reference Brown D, Christine K, Showell C, Conlon F. Small heat shock protein Hsp27 is required for proper heart tube formation. Genesis. 2007;45:667–78.CrossRef Brown D, Christine K, Showell C, Conlon F. Small heat shock protein Hsp27 is required for proper heart tube formation. Genesis. 2007;45:667–78.CrossRef
22.
go back to reference Hickson L, Negrotto S, Onuigbo M, Scott C, Rule A, Norby S, et al. Echocardiography criteria for structural heart disease in patients with end-stage renal disease initiating hemodialysi. J Am Coll Cardiol. 2016;67:1173–82.CrossRef Hickson L, Negrotto S, Onuigbo M, Scott C, Rule A, Norby S, et al. Echocardiography criteria for structural heart disease in patients with end-stage renal disease initiating hemodialysi. J Am Coll Cardiol. 2016;67:1173–82.CrossRef
23.
go back to reference Lang R, Badano L, Mor-Avi V, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2015;28:1–39.CrossRef Lang R, Badano L, Mor-Avi V, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2015;28:1–39.CrossRef
24.
go back to reference Jaroszyński A, Czekajska-Chechab E, Drelich-Zbroja A, Zapolski T, Książek A. Spatial QRS-T angle in peritoneal dialysis patients: association with carotid artery atherosclerosis, coronary artery calcification and troponin T. Nephrol Dial Transplant. 2009;24:1003–8.CrossRef Jaroszyński A, Czekajska-Chechab E, Drelich-Zbroja A, Zapolski T, Książek A. Spatial QRS-T angle in peritoneal dialysis patients: association with carotid artery atherosclerosis, coronary artery calcification and troponin T. Nephrol Dial Transplant. 2009;24:1003–8.CrossRef
26.
go back to reference Jaroszyński A, Jaroszyńska SJ, Dąbrowski W, Niedziałek J, Bednarek-Skublewska A, Zapolski T, et al. The prognostic value of positive T-wave in lead aVR in hemodialysis patients. Clin Exp Nephrol. 2015;19:1157–64.CrossRef Jaroszyński A, Jaroszyńska SJ, Dąbrowski W, Niedziałek J, Bednarek-Skublewska A, Zapolski T, et al. The prognostic value of positive T-wave in lead aVR in hemodialysis patients. Clin Exp Nephrol. 2015;19:1157–64.CrossRef
27.
go back to reference Nakayoshi T, Adachi H, Ohbu-Murayama K, et al. Plasma heat shock protein 27 is increased in renal dysfunction and habitual smoking in a Japanese general population. J Cardiol. 2016;67:110–4.CrossRef Nakayoshi T, Adachi H, Ohbu-Murayama K, et al. Plasma heat shock protein 27 is increased in renal dysfunction and habitual smoking in a Japanese general population. J Cardiol. 2016;67:110–4.CrossRef
28.
go back to reference Lebherz-Eichinger D, Ankersmit H, Hacker S, et al. HSP27 and HSP70 serum and urinelevels in patients suffering from chronic kidney disease. Clin Chim Acta. 2012;413:282–6.CrossRef Lebherz-Eichinger D, Ankersmit H, Hacker S, et al. HSP27 and HSP70 serum and urinelevels in patients suffering from chronic kidney disease. Clin Chim Acta. 2012;413:282–6.CrossRef
29.
go back to reference Traxler D, Lainscak M, Simader E, Ankersmit H, Jug B. Heat shock protein 27 acts as a predictor of prognosis in chronic heart failure patients. Clin Chim Acta. 2017;473:127–32.CrossRef Traxler D, Lainscak M, Simader E, Ankersmit H, Jug B. Heat shock protein 27 acts as a predictor of prognosis in chronic heart failure patients. Clin Chim Acta. 2017;473:127–32.CrossRef
30.
go back to reference Martin-Ventura J, Duran M, Blanco-Colio L, et al. Identification by a differential proteomic approach of heat shock protein 27 as a potential marker of a atherosclerosis. Circulation. 2004;110:2216–9.CrossRef Martin-Ventura J, Duran M, Blanco-Colio L, et al. Identification by a differential proteomic approach of heat shock protein 27 as a potential marker of a atherosclerosis. Circulation. 2004;110:2216–9.CrossRef
32.
go back to reference Mohammadpour A, Nazemian F, Moallem S, Alamdaran S, Asad-Abadi E, Shamsara J. Correlation between heat-shock protein 27 serum concentration and common carotid intima-media thickness in hemodialysis patients. Iran J Kidney Dis. 2011;5:260–6.PubMed Mohammadpour A, Nazemian F, Moallem S, Alamdaran S, Asad-Abadi E, Shamsara J. Correlation between heat-shock protein 27 serum concentration and common carotid intima-media thickness in hemodialysis patients. Iran J Kidney Dis. 2011;5:260–6.PubMed
33.
go back to reference Rayner K, Chen Y, Siebert T, O’Brien E. Heat shock protein 27: clue to understanding estrogen-mediated atheroprotection? Trends Cardiovasc Med 2010; 20 : 53–57. Rayner K, Chen Y, Siebert T, O’Brien E. Heat shock protein 27: clue to understanding estrogen-mediated atheroprotection? Trends Cardiovasc Med 2010; 20 : 53–57.
35.
go back to reference Himmelfarb J, Stenvinkel P, Ikizler T, Hakim R. The elephant in uremia: oxidant stress as a unifying concept of cardiovascular disease in uremia. Kidney Int. 2002;62:1524–38.CrossRef Himmelfarb J, Stenvinkel P, Ikizler T, Hakim R. The elephant in uremia: oxidant stress as a unifying concept of cardiovascular disease in uremia. Kidney Int. 2002;62:1524–38.CrossRef
39.
go back to reference Ortiz A, Covic A, Fliser D, et al. Board of the EURECA-m Working Group of ERA-EDTA. Epidemiology, contributors to, and clinicaltrials of mortality risk in chronic kidney failure. Lancet. 2014;383:1831–43.CrossRef Ortiz A, Covic A, Fliser D, et al. Board of the EURECA-m Working Group of ERA-EDTA. Epidemiology, contributors to, and clinicaltrials of mortality risk in chronic kidney failure. Lancet. 2014;383:1831–43.CrossRef
41.
go back to reference Solbu M, Mjøen G, Mark P, et al. Predictors of atherosclerotic events in patients on haemodialysis: post hoc analyses from the AURORA study. Nephrol Dial Transplant. 2018;33:102–12.PubMed Solbu M, Mjøen G, Mark P, et al. Predictors of atherosclerotic events in patients on haemodialysis: post hoc analyses from the AURORA study. Nephrol Dial Transplant. 2018;33:102–12.PubMed
42.
go back to reference Stepp D, Ou J, Ackerman A, Welak S, Klick D, Pritchard K. Native LDL and minimalny oxidized LDL differentially regulate superoxide anion in vascular endothelium in situ. Am J Physiol Heart Circ Physiol. 2002;283:750–9.CrossRef Stepp D, Ou J, Ackerman A, Welak S, Klick D, Pritchard K. Native LDL and minimalny oxidized LDL differentially regulate superoxide anion in vascular endothelium in situ. Am J Physiol Heart Circ Physiol. 2002;283:750–9.CrossRef
44.
go back to reference Antunovic T, Stefanovic A, Gligorovic Barhanovic N, et al. Prooxidant-antioxidant balance, hsTnI and hsCRP: mortality prediction in haemodialysis patients, two-year follow-up. Ren Fail. 2017;39:491–9.CrossRef Antunovic T, Stefanovic A, Gligorovic Barhanovic N, et al. Prooxidant-antioxidant balance, hsTnI and hsCRP: mortality prediction in haemodialysis patients, two-year follow-up. Ren Fail. 2017;39:491–9.CrossRef
45.
go back to reference Wu J, Liu T, Rios Z, Mei Q, Lin X, Cao S. Heat shock proteins and Cancer. Trends Pharmacol Sci. 2017;38:226–56.CrossRef Wu J, Liu T, Rios Z, Mei Q, Lin X, Cao S. Heat shock proteins and Cancer. Trends Pharmacol Sci. 2017;38:226–56.CrossRef
Metadata
Title
Serum heat shock protein 27 levels predict cardiac mortality in hemodialysis patients
Authors
Andrzej Jaroszyński
Anna Jaroszyńska
Tomasz Zaborowski
Anna Drelich-Zbroja
Tomasz Zapolski
Wojciech Dąbrowski
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Nephrology / Issue 1/2018
Electronic ISSN: 1471-2369
DOI
https://doi.org/10.1186/s12882-018-1157-1

Other articles of this Issue 1/2018

BMC Nephrology 1/2018 Go to the issue