Atrial Heat Shock Protein levels are associated with early post-operative and persistence of atrial fibrillation

There is a great need for markers to detect and stage AF to subsequently start patient-tailored therapy. Despite the fact that several blood-based markers are routinely measured in clinical practice, they lack in sufficient specificity for AF. Similar to our previous study in AF patients treated with electrocardioversion and ablative therapy, no role for serum HSPB1, HSPA1, HSPB7 or HSPD1 levels to stage AF in patients undergoing cardiac surgery was found. For HSPA1, this is in line with other studies Hu Y.F. Yeh H.I. Tsao H.M. Tai C.T. Lin Y.J. Chang S.L. Lo L.W. Tuan T.C. Suenari K. Li C.H. Chao T.F. Chen S.A. Electrophysiological correlation and prognostic impact of heat shock protein 27 in atrial fibrillation.,Kornej J. Reinhardt C. Kosiuk J. Arya A. Hindricks G. Adams V. Husser D. Bollmann A. Response of circulating heat shock protein 70 and anti-heat shock protein 70 antibodies to catheter ablation of atrial fibrillation.. Yet, for HSPB1, our findings are in contrast to findings in the report of Hu, et al. Hu Y.F. Yeh H.I. Tsao H.M. Tai C.T. Lin Y.J. Chang S.L. Lo L.W. Tuan T.C. Suenari K. Li C.H. Chao T.F. Chen S.A. Electrophysiological correlation and prognostic impact of heat shock protein 27 in atrial fibrillation.. Serum HSPB1 levels were found to be associated with history of AF, as HSPB1 levels were reduced in ParAF and LSPerAF patients compared to controls in sinus rhythm Hu Y.F. Yeh H.I. Tsao H.M. Tai C.T. Lin Y.J. Chang S.L. Lo L.W. Tuan T.C. Suenari K. Li C.H. Chao T.F. Chen S.A. Electrophysiological correlation and prognostic impact of heat shock protein 27 in atrial fibrillation.. For HSPD1, no association between its serum levels and history of AF was found by Maan, et al. Maan A. Jorgensen N.W. Mansour M. Dudley S. Jenny N.S. Defilippi C. Szklo M. Alonso A. Refaat M.M. Ruskin J. Heckbert S.R. Heist E.K. Association between Heat Shock Protein-60 and Development of Atrial Fibrillation: Results from the Multi-Ethnic Study of Atherosclerosis (MESA).. However, Cao, et al. Cao H. Xue L. Xu X. Wu Y. Zhu J. Chen L. Chen D. Chen Y. Heat shock proteins in stabilization of spontaneously restored sinus rhythm in permanent atrial fibrillation patients after mitral valve surgery. described that patients undergoing mitral valve replacement with AF revealed higher plasma HSPD1 levels compared to patients in sinus rhythm. No previous studies, except for our recent study Marion D. Lanters E.A.H. Ramos K.S. Li J. Wiersma M. Baks-Te Bulte L. JQMM A. Boersma E. de Groot N.M.S. Brundel B. Evaluating Serum Heat Shock Protein Levels as Novel Biomarkers for Atrial Fibrillation., investigated serum HSPB7 as a marker to stage AF.Previous studies revealed an increase in HSPB1 levels Marion D. Lanters E.A.H. Ramos K.S. Li J. Wiersma M. Baks-Te Bulte L. JQMM A. Boersma E. de Groot N.M.S. Brundel B. Evaluating Serum Heat Shock Protein Levels as Novel Biomarkers for Atrial Fibrillation. and HSPA1 levels Kornej J. Reinhardt C. Kosiuk J. Arya A. Hindricks G. Adams V. Husser D. Bollmann A. Response of circulating heat shock protein 70 and anti-heat shock protein 70 antibodies to catheter ablation of atrial fibrillation. in follow-up serum samples of patients who developed AF recurrence post-ablative therapy. Such an increase in HSPs in follow-up serum samples was not observed in the current study, which may be due to presence of underlying heart diseases. Here, RAA levels of HSPA5 as well as both RAA and LAA HSPD1 levels may have value to indicate more persistent stages of AF. Lower RAA levels of the endoplasmic reticulum (ER) chaperone-protein HSPA5 correlates with LSPerAF, and its values are increased in RAA of control patients with PoAF and in LAA of AF patients showing AF recurrence. These findings suggest a role for ER stress to contribute to AF onset. Previously, Wiersma et al. showed induction of HSPA5 expression to attenuate AF-induced ER stress and downstream excessive activation of autophagic protein degradation pathway as protective mechanism against AF promotion Wiersma M. Meijering R.A.M. Qi X.Y. Zhang D. Liu T. Hoogstra-Berends F. Sibon O.C.M. Henning R.H. Nattel S. Brundel B. Endoplasmic Reticulum Stress Is Associated With Autophagy and Cardiomyocyte Remodeling in Experimental and Human Atrial Fibrillation.. In line, higher levels of HSPA5, as observed in patients with PoAF and AF recurrence after arrhythmia surgery, may indicate the presence of ER stress and activation of compensatory mechanisms. In LSPerAF patients, low intracellular levels of HSPA5 may indicate exhaustion of the ER chaperone, ER stress and autophagic protein degradation. Regarding the mitochondrial stress marker HSPD1, previous findings have shown higher mitochondrial stress markers in more persistent stages of AF, suggesting a role for mitochondria in AFWiersma M. van Marion D.M.S. Wust R.C.I. Houtkooper R.H. Zhang D. Groot N.M.S. Henning R.H. Brundel B. Mitochondrial Dysfunction Underlies Cardiomyocyte Remodeling in Experimental and Clinical Atrial Fibrillation.. The mitochondrial HSPs, HSPD1 and HSPE1, were more than doubled in the atrial myocardium of patients with persistent AF compared to control patients who underwent CABG and/or valve surgery Schafler A.E. Kirmanoglou K. Balbach J. Pecher P. Hannekum A. Schumacher B. The expression of heat shock protein 60 in myocardium of patients with chronic atrial fibrillation.,Schafler A.E. Kirmanoglou K. Pecher P. Hannekum A. Schumacher B. Overexpression of heat shock protein 60/10 in myocardium of patients with chronic atrial fibrillation.. Higher HSPD1 levels in patients with AF were confirmed in the study of Cao, et al. Cao H. Xue L. Xu X. Wu Y. Zhu J. Chen L. Chen D. Chen Y. Heat shock proteins in stabilization of spontaneously restored sinus rhythm in permanent atrial fibrillation patients after mitral valve surgery.. In the same study, HSPB1, HSPA1 and HSF1 tissue levels were lower in patients with AF, compared to patients without history of AF Cao H. Xue L. Xu X. Wu Y. Zhu J. Chen L. Chen D. Chen Y. Heat shock proteins in stabilization of spontaneously restored sinus rhythm in permanent atrial fibrillation patients after mitral valve surgery.. Other studies found HSPB1 levels to be increased in ParAF in comparison with patients in sinus rhythm and PerAF Brundel B.J. Henning R.H. Ke L. van Gelder I.C. Crijns H.J. Kampinga H.H. Heat shock protein upregulation protects against pacing-induced myolysis in HL-1 atrial myocytes and in human atrial fibrillation.,Yang M. Tan H. Cheng L. He M. Wei Q. Tanguay R.M. Wu T. Expression of heat shock proteins in myocardium of patients with atrial fibrillation., however such an increase was not found for HSPA1. While our findings for HSPB1, HSPA1, HSPA5, HSPB5 and pHSF1 are not reaching consensus with all other reports, HSPD1 RAA and LAA levels are indicative for more persistent stages of AF in combination with underlying heart diseases. Interestingly, studies have shown influence of statins modulating HSPs expression, nevertheless we did observe similar serum HSPB1, HSPA1, HSPB7 and HSPD1 expression between AF groups (higher intake of statins) and control.

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