Key result
Ventricular tachypacing-induced CHF decreases HSP27 phosphorylation at serine-78 versus controls despite unchanged overall HSP expression.
Why the study?
Studies examining heat shock protein expression in patients with AF have yielded mixed results, prompting the use of canine models to reproducibly investigate the role of HSPs in AF pathophysiology.
Does atrial or ventricular tachypacing alter the expression and phosphorylation of heat shock proteins in canine models?
Does atrial or ventricular tachypacing alter the expression and phosphorylation of heat shock proteins in canine models?
p-value: p=<0.0111
Atrial and ventricular tachypacing in canine models do not alter total HSP expression but decrease HSP27 phosphorylation, suggesting post-translational modifications play a role in AF pathophysiology.
Decreased HSP27 phosphorylation in canine tachypacing models should not change practice; leaves open a post-translational role in AF requiring human validation.
BACKGROUND: Uncontrolled atrial fibrillation (AF) results in complex changes in the cardiomyocyte electrical and contractile functioning that promote atrial remodeling and the continuation of AF. Recently there has been a growing interest in understanding the role of heat shock proteins (HSPs), which are cytoprotective molecular chaperones, in the pathophysiology of AF. Several groups have examined HSP expression in patients with AF but have yielded mixed results. To allow for better consistency and reproducibility between subjects, we utilized canine models to reproduce AFpromoting conditions to better investigate the role of HSPs in the pathophysiology of AF. METHODS: AF promoting conditions were simulated in canine models with fifteen adult mongrel dogs (20.6 to 36.0 kg) divided into three groups: (1) Control (n=5), (2) two week ventricular tachypacing (VTP) induced congestive heart failure (CHF) (n=5), and (3) one week atrial tachypacying (ATP) (n=5). Quick frozen right atrial free wall tissue samples were used for protein isolation and were analyzed via Western blotting with data was expressed as a relative ratio and were analyzed using a two-tailed, unpaired ttest and significance was set at p < 0.05. The expression levels of HSP 90, 70, and 25 were studied along with the phosphorylation status of HSP27 at serine-78. RESULTS: We first examined the effects of the ATP and CHF heart models on the expression of a select group of HSPs via Western Blot. We found that there was no significant difference in levels of expression of HSP 90, 70, or 25 when either ATP or CHF models were compared to control canines. The phosphorylation status of HSP27 was significantly decreased in the CHF canine model when compared to control (p < 0.0111) and it tended towards a decrease in the ATP canine model when compared to control (p=0.0923). CONCLUSION: This study showed that even though the expression levels of HSPs may remain constant, there are protein phosphorylation and dephosphorylation events that occur in AF that may have important consequences in its pathophysiology. It is therefore necessary to investigate the full scale of HSP modifications during AF and AF-promoting conditions.
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Shorofsky et al. (2020) studied Atrial fibrillation (simulated) (n=15). Atrial or ventricular tachypacing vs. Control (no tachypacing) was evaluated on Phosphorylation status of HSP27 at serine-78 (p=<0.0111). Ventricular tachypacing-induced congestive heart failure significantly decreased the phosphorylation status of HSP27 at serine-78 compared to controls (p < 0.0111), with no change in overall HSP expression.
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