The small heat shock protein 20 (HSPB6) emerges as a potential upstream mediator of autophagy. Although autophagy is linked to several clinical disorders, how HSPB6 and autophagy are regulated in the setting of heart failure (HF) remains unknown. The goal of this study was to assess activation of the HSPB6 and its association with other well-established autophagy markers in central and peripheral tissues from a preclinical Ossabaw swine model of cardio-metabolic HF induced by Western diet and chronic cardiac pressure-overload. We hypothesized HSPB6 would be activated in central and peripheral tissues, stimulating autophagy. We found that autophagy in the heart is interrupted at various stages of the process in a chamber-specific manner. Protein levels of HSPB6, Beclin 1, and p62 are increased in the right ventricle, while only HSPB6 was increased in the left ventricle. Unlike the heart, samples from the triceps brachii long head showed only an increase in the protein level of p62, highlighting interesting central versus peripheral differences in autophagy regulation. In the right coronary artery, total HSPB6 protein expression was decreased and associated with an increase in LC3B-II/LC3B-I ratio, demonstrating a different mechanism of autophagy dysregulation in the coronary vasculature. Thus, contrary to our hypothesis, activation of HSPB6 was differentially regulated in a tissue-specific manner and observed in parallel with variable states of autophagy markers assessed by protein levels of LC3B, p62, and Beclin 1. Our data provide insight into how the HSPB6/autophagy axis is regulated in a preclinical swine model with potential relevance to HFpEF.

中文翻译：

---

组织特异性小热休克蛋白20激活与患有心脏代谢性心力衰竭的Ossabaw猪的传统自噬标记物无关。

小型热激蛋白20（HSPB6）成为自噬的潜在上游介质。尽管自噬与几种临床疾病有关，但是如何在心力衰竭（HF）的环境中调节HSPB6和自噬仍是未知的。这项研究的目的是评估由西方饮食和慢性心脏超负荷引起的心源性代谢性HF的临床前Ossabaw猪模型在中枢和外周组织中HSPB6的激活及其与其他公认的自噬标记的关联。我们假设HSPB6将在中枢和外周组织中被激活，从而刺激自噬。我们发现，心脏的自噬在该过程的各个阶段以特定于腔室的方式被中断。HSPB6，Beclin 1和p62的蛋白质水平在右心室增加，左心室仅HSPB6升高。与心脏不同，肱三头肌长头样本仅显示p62蛋白水平升高，突显了自噬调节中有趣的中枢与外周差异。在右冠状动脉中，总HSPB6蛋白表达降低，并与LC3B-II / LC3B-I比值增加相关，证明了冠状血管中自噬失调的不同机制。因此，与我们的假设相反，以组织特异性方式对HSPB6的激活进行了差异调节，并与通过LC3B，p62和Beclin 1的蛋白质水平评估的自噬标记物的可变状态并行观察到。我们的数据提供了对HSPB6的了解。 /自噬轴在临床前的猪模型中受到调控，与HFpEF具有潜在的相关性。