Evaluating Serum Heat Shock Protein Levels as Novel Biomarkers for Atrial Fibrillation

Background: Staging of atrial fibrillation (AF) is essential to understanding disease progression and the accompanied increase in therapy failure. Blood-based heat shock protein (HSP) levels may enable staging of AF and the identification of patients with higher risk for AF recurrence after treatment. Objective: This study evaluates the relationship between serum HSP levels, presence of AF, AF stage and AF recurrence following electrocardioversion (ECV) or pulmonary vein isolation (PVI). Methods: To determine HSP27, HSP70, cardiovascular (cv)HSP and HSP60 levels, serum samples were collected from control patients without AF and patients with paroxysmal atrial fibrillation (PAF), persistent (PeAF) and longstanding persistent (LSPeAF) AF, presenting for ECV or PVI, prior to intervention and at 3-, 6- and 12-months post-PVI. Results: The study population (n = 297) consisted of 98 control and 199 AF patients admitted for ECV (n = 98) or PVI (n = 101). HSP27, HSP70, cvHSP and HSP60 serum levels did not differ between patients without or with PAF, PeAF or LSPeAF. Additionally, baseline HSP levels did not correlate with AF recurrence after ECV or PVI. However, in AF patients with AF recurrence, HSP27 levels were significantly elevated post-PVI relative to baseline, compared to patients without recurrence. Conclusions: No association was observed between baseline HSP levels and the presence of AF, AF stage or AF recurrence. However, HSP27 levels were increased in serum samples of patients with AF recurrence within one year after PVI, suggesting that HSP27 levels may predict recurrence of AF after ablative therapy.

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Abstract P172: Circulating Heat Shock Protein 70 and Antiheat Shock Protein 70 Antibodies in Atrial Fibrillation: Relation with Atrial Fibrillation Type and Response to Catheter Ablation

Circulation Research ◽

10.1161/res.109.suppl_1.ap172 ◽

2011 ◽

Vol 109 (suppl_1) ◽

Author(s):

Jelena Kornej ◽

Claudia Reinhardt ◽

Jedrzej Kosiuk ◽

Arash Arya ◽

Gerhard Hindricks ◽

...

Keyword(s):

Atrial Fibrillation ◽

Regression Analysis ◽

Catheter Ablation ◽

Heat Shock ◽

Heat Shock Protein ◽

Heat Shock Protein 70 ◽

Recurrence Rates ◽

Multivariable Regression Analysis ◽

Multivariable Regression ◽

Af Recurrence

Background: HSP and anti-HSP antibodies have been associated with AF development and progression. This study investigated the possible association between circulating heat shock protein 70 (HSP70) and anti-HSP70 antibodies as well their changes and rhythm outcome after atrial fibrillation (AF) catheter ablation. Methods: In 67 patients with AF (59±11 years, 66 % male, 66 % lone AF) undergoing catheter ablation, circulating HSP70 and anti-HSP70 antibodies levels were quantified before and 6 months after catheter ablation. Serial 7-day Holter ECGs were used to detect AF recurrences. Results: At baseline, HSP70 was detectable in 14 patients (21 %), but there was no correlation between clinical or echocardiographic variables and the presence or the level of HSP70. Patients with paroxysmal AF (n=39) showed lower anti-HSP70 antibodies (median 43, IQR 28 - 62 µg/ml) than patients with persistent AF (n=28; 53, 41 - 85 µg/ml, p=.035). Using multivariable regression analysis, AF type was the only variable associated with anti-HSP70 antibodies (Beta=.342, p=.008). At 6 months, HSP70 was present in 27 patients (41 %, p<.001 vs. baseline) with an overall increase (median 0, IQR 0 - 0 vs. 0, 0 - 0.09 ng/ml, p=.029). Similarly, there was an increase of anti-HSP70 antibodies (48, 36 - 72 vs. 57, 43 - 87 µg/ml, p<.001). AF recurrence rates were higher in patients with HSP70 increase >0.025 ng/ml (32 vs. 11 %, p=.038) or anti-HSP70 antibodies increase >2.5 µg/ml (26 vs. 4 %, p=.033). Conclusion: HSP70 and anti-HSP70 antibodies may be involved in the progression of AF and AF recurrence after catheter ablation.

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

Heart Rhythm ◽

10.1016/j.hrthm.2021.06.1194 ◽

2021 ◽

Author(s):

Denise M.S. van Marion ◽

Kennedy S. Ramos ◽

Eva A.H. Lanters ◽

Luciënne Baks-te Bulte ◽

Ad J.J.C. Bogers ◽

...

Keyword(s):

Atrial Fibrillation ◽

Heat Shock ◽

Heat Shock Protein ◽

Protein Levels

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Serum heat shock protein 70 levels as a biomarker for inflammatory processes in multiple sclerosis

Multiple Sclerosis Journal - Experimental Translational and Clinical ◽

10.1177/2055217318767192 ◽

2018 ◽

Vol 4 (2) ◽

pp. 205521731876719 ◽

Cited By ~ 3

Author(s):

Patricia Lechner ◽

Dorothea Buck ◽

Lisa Sick ◽

Bernhard Hemmer ◽

Gabriele Multhoff

Keyword(s):

Multiple Sclerosis ◽

Heat Shock ◽

Heat Shock Protein ◽

Heat Shock Protein 70 ◽

Neurological Diseases ◽

Serum Levels ◽

Enzyme Linked Immunosorbent Assay ◽

Serum Samples ◽

Potential Biomarker ◽

Inflammatory Processes

Background Inflammatory and neurodegenerative processes are hallmarks of multiple sclerosis (MS). The synthesis of the major stress-inducible heat shock protein 70 (Hsp70) is induced by inflammation. Objective The purpose of this study is to determine whether Hsp70 in serum can serve as a potential biomarker to distinguish inflammatory and neurodegenerative processes in MS. Methods Serum was obtained from 94 patients: 26 clinically isolated syndrome (CIS), 40 relapsing–remitting MS (RRMS), 19 secondary progressive MS (SPMS), and nine primary progressive MS (PPMS). As controls, serum samples were collected from patients with non-inflammatory neurological diseases (NINDs, n = 41), other inflammatory neurological diseases (OINDs, n = 28) and healthy donors (HDs, n = 114). Serum levels of Hsp70 were quantified using the enzyme-linked immunosorbent assay detecting free and liposomal Hsp70 (lipHsp70 ELISA). Results Patients with MS displayed significantly higher Hsp70 serum levels than HDs ( p < 0.001) and significantly lower levels than OINDs ( p = 0.001). A subgroup analysis revealed that Hsp70 serum levels of CIS/RRMS patients are significantly higher than those of patients with progressive MS (SPMS/PPMS) ( p < 0.05). Conclusion Inflammation causes the release of Hsp70 into the blood. As CIS/RRMS are associated with higher Hsp70 serum levels than progressive MS, serum Hsp70 levels might provide a marker for inflammatory processes.

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Association of Met439Thr Substitution in Heat Shock Protein 70 Gene with Postoperative Atrial Fibrillation and Serum HSP70 Protein Levels

Cardiology ◽

10.1159/000109406 ◽

2008 ◽

Vol 110 (1) ◽

pp. 45-52 ◽

Cited By ~ 32

Author(s):

Ali R. Afzal ◽

Kaushik Mandal ◽

Samuel Nyamweya ◽

Georgios Foteinos ◽

Jan Poloniecki ◽

...

Keyword(s):

Atrial Fibrillation ◽

Heat Shock ◽

Heat Shock Protein ◽

Heat Shock Protein 70 ◽

Postoperative Atrial Fibrillation ◽

Protein Levels ◽

Hsp70 Protein

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Heterophil/lymphocyte ratios and heat-shock protein levels are related to growth in nestling birds

Ecoscience ◽

10.1080/11956860.2002.11682731 ◽

2002 ◽

Vol 9 (4) ◽

pp. 434-439 ◽

Cited By ~ 85

Author(s):

Juan Moreno ◽

Santiago Merino ◽

Javier MartÍnez ◽

Juan Sanz ◽

Elena Arriero

Keyword(s):

Heat Shock ◽

Heat Shock Protein ◽

Protein Levels

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Abstract 13793: Role of Cardiac Autoantibodies for the Prediction of Recurrence Following Cryoballoon-based Lone Atrial Fibrillation Ablation

Circulation ◽

10.1161/circ.130.suppl_2.13793 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Muhammed U Yalcin ◽

Kadri M Gurses ◽

Duygu Kocyigit ◽

Sacit A Kesikli ◽

Hikmet Yorgun ◽

...

Keyword(s):

Atrial Fibrillation ◽

Predictive Value ◽

Cox Regression ◽

Muscarinic Acetylcholine Receptor ◽

Left Atrial Volume ◽

Volume Index ◽

Lone Atrial Fibrillation ◽

Left Atrial Volume Index ◽

One Year ◽

Af Recurrence

Introduction: Recent evidence have suggested that autoantibodies may play an important role in the development of atrial fibrillation (AF). Predictive value of pre-procedural autoantibodies against beta-1 adrenergic receptor (anti-β1-R) and M2-muscarinic acetylcholine receptor (anti-M2-R) for AF recurrence following cryoballoon-based pulmonary vein isolation (PVI) is still unclear. We aimed to determine the predictive value of pre-procedural anti-β1-R and anti-M2-R levels for AF recurrence in lone AF patients following cryoballoon-based PVI. METHODS: 80 patients (mean age 54.25±7.7 years; 40% males) with lone AF who underwent cryoballoon-based PVI were included in the study. Pre-procedural anti-M2-R and anti-β1-R levels were measured with ELISA. RESULTS: At one-year follow-up after ablation, late AF recurrence was observed in 17 (21.25%) patients. In the Cox regression model including number of antiarrhythmic drugs, early AF recurrence, anti-β1-R levels >159.88 ng/mL, anti-M2-R levels >277.65 ng/mL, AF duration and left atrial volume index; only anti-β1-R levels >159.88 ng/mL (HR: 4.281, p=0.039) and anti-M2-R levels >277.65 ng/mL (HR: 4.313, p=0.030) were found to be independent predictors of late AF recurrence. Anti-β1-R level >159.88 ng/mL was shown to predict late AF recurrence with a sensitivity of 70.59% and specificity of 90.48%. A cut-off value of 277.65 ng/mL for anti-M2-R level predicted AF recurrence with a sensitivity of 70.59% and specificity of 95.24%. CONCLUSION: Pre-procedural serum anti-β1-R and anti-M2-R levels are independent predictors of late AF recurrence following cryoballoon-based PVI in lone AF patients. Detection of pre-procedural anti-β1-R and anti-M2-R levels may serve as a novel method for determination of lone AF patients who may not benefit from cryoballoon-based PVI.

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Feeding rates affect heat shock protein levels in liver of larval white sturgeon(Acipenser transmontanus)

Aquaculture ◽

10.1016/j.aquaculture.2008.10.041 ◽

2009 ◽

Vol 287 (1-2) ◽

pp. 223-226 ◽

Cited By ~ 32

Author(s):

Dong-Fang Deng ◽

Chunfang Wang ◽

Seunghyung Lee ◽

Sungchul Bai ◽

Silas S.O. Hung

Keyword(s):

Heat Shock ◽

Heat Shock Protein ◽

White Sturgeon ◽

Acipenser Transmontanus ◽

Feeding Rates ◽

Protein Levels

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Pulmonary prophylactic impact of melatonin and/or quercetin: A novel therapy for inflammatory hypoxic stress in rats

Acta Pharmaceutica ◽

10.1515/acph-2017-0010 ◽

2017 ◽

Vol 67 (1) ◽

pp. 125-135 ◽

Cited By ~ 7

Author(s):

Nouf M. Al-Rasheed ◽

Laila Fadda ◽

Hala A. Attia ◽

Iman A. Sharaf ◽

Azza M. Mohamed ◽

...

Keyword(s):

Heat Shock ◽

Heat Shock Protein ◽

Lung Tissue ◽

Inflammatory Mediators ◽

Histopathological Examination ◽

Serum Levels ◽

Control Group ◽

Novel Therapy ◽

Protein Expressions ◽

Pre Treatment

AbstractThe study aims to compare, through histological and biochemical studies, the effects of quercetin, melatonin and their combination in regulation of immuno-inflammatory mediators and heat shock protein expressions in sodium nitrite induced hypoxia in rat lungs. The results revealed that NaNO2injection caused a significant decrease in Hb in rats, while serum levels of TNF-α, IL-6 and CRP, VEGF and HSP70 were elevated compared to the control group. Administration of melatonin, quercetin or their combination before NaNO2injection markedly reduced these parameters. Histopathological examination of the lung tissue supported these biochemical findings. The study suggests that melatonin and/or quercetin are responsible for lung tissue protection in hypoxia by downregulation of immuno-inflammatory mediators and heat shock protein expressions. Pre-treatment of hypoxic animals with a combination of melatonin and quercetin was effective in modulating most of the studied parameters to near-normal levels.

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Abstract 15934: Comparison of Atrial Fibrillation Burden Reduction in Patients With Paroxysmal and Persistent Atrial Fibrillation Undergoing Cryoballoon Pulmonary Vein Isolation

Circulation ◽

10.1161/circ.142.suppl_3.15934 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Dan L Musat ◽

Nicolle S Milstein ◽

Jacqueline Pimienta ◽

Advay Bhatt ◽

Tina C Sichrovsky ◽

...

Keyword(s):

Atrial Fibrillation ◽

Pulmonary Vein ◽

Pulmonary Vein Isolation ◽

Persistent Atrial Fibrillation ◽

Loop Recorder ◽

Similar Reduction ◽

Af Ablation ◽

Ablation Success ◽

One Year ◽

Af Recurrence

Background: Pulmonary vein isolation (PVI) is a cornerstone of atrial fibrillation (AF) ablation procedures to treat symptomatic AF. Ablation success is defined by absence of AF recurrence >30 seconds. However, reduction in AF burden (AFB) is also an important endpoint. Whether patients with paroxysmal (PAF) and persistent AF (PeAF) have similar reduction in AFB post-ablation is unknown. Objective: To compare the decrease in AFB following cryoballoon (CB) PVI in patients with PAF and PeAF. Methods: We enrolled consecutive pts with an implantable loop recorder (ILR) who subsequently underwent CB PVI. All patients were followed prospectively for at least one year, or until repeat ablation; we compared AFB pre and post-ablation. Results: The cohort included had 47 patients (66 ± 10 years; 32 [68%] male; PAF [n=23, 49%]; CHA 2 DS 2 -VASc 2.7 ± 1.7, 34 [72%] on AAD at the time of ablation). A median of 136 days [IQR 280, 73; minimum of 30 days] of ILR data pre-ablation were available. The median AFB for PAF was 4.7% [IQR 0.9, 14.8] and PeAF was 6.8% [IQR 1.1, 40.4]. After excluding a 3-month post-ablation blanking period, recurrent AF occurred in 12 (52%) PAF and 11 (46%) PeAF patients. The median AFB post-ablation for PAF and PeAF cohorts was 0.03%, [IQR 0, 0.3] and 0.04%, [IQR 0, 1.1], respectively. This represents a >99% reduction in AFB. Conclusion: Although 50% of patients undergoing CB PVI for PAF or PeAF had a recurrence of AF, there was >99% reduction in AFB in both groups. These data highlight the importance of using AFB burden as a marker of therapeutic efficacy post-AF ablation.

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Daily Supplementation of L-Glutamine in Atrial Fibrillation Patients: The Effect on Heat Shock Proteins and Metabolites

Cells ◽

10.3390/cells9071729 ◽

2020 ◽

Vol 9 (7) ◽

pp. 1729 ◽

Cited By ~ 2

Author(s):

Roeliene Starreveld ◽

Kennedy S. Ramos ◽

Agnes J. Q. M. Muskens ◽

Bianca J. J. M. Brundel ◽

Natasja M. S. de Groot

Keyword(s):

Atrial Fibrillation ◽

Heat Shock ◽

Metabolic Pathways ◽

Serum Levels ◽

Therapeutic Strategies ◽

Glutamine Supplementation ◽

Novel Therapies ◽

Cardioprotective Effects ◽

Baseline Levels ◽

Shock Proteins

Pharmaco-therapeutic strategies of atrial fibrillation (AF) are moderately effective and do not prevent AF onset and progression. Therefore, there is an urgent need to develop novel therapies. Previous studies revealed heat shock protein (HSP)-inducing compounds to mitigate AF onset and progression. Such an HSP inducing compound is L-glutamine. In the current study we investigate the effect of L-glutamine supplementation on serum HSP27 and HSP70 levels and metabolite levels in patients with AF patients (n = 21). Hereto, HSP27 and HSP70 levels were determined by ELISAs and metabolites with LC-mass spectrometry. HSP27 levels significantly decreased after 3-months of L-glutamine supplementation [540.39 (250.97–1315.63) to 380.69 (185.68–915.03), p = 0.004] and normalized to baseline levels after 6-months of L-glutamine supplementation [634.96 (139.57–3103.61), p < 0.001]. For HSP70, levels decreased after 3-months of L-glutamine supplementation [548.86 (31.50–1564.51) to 353.65 (110.58–752.50), p = 0.045] and remained low after 6-months of L-glutamine supplementation [309.30 (118.29–1744.19), p = 0.517]. Patients with high HSP27 levels at baseline showed normalization of several metabolites related to the carbohydrates, nucleotides, amino acids, vitamins and cofactors metabolic pathways after 3-months L-glutamine supplementation. In conclusion, L-glutamine supplementation reduces the serum levels of HSP27 and HSP70 within 3-months and normalizes metabolite levels. This knowledge may fuel future clinical studies on L-glutamine to improve cardioprotective effects that may attenuate AF episodes.

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