Aims

HSP70, a molecular chaperone, helps to maintain proteostasis. In muscle biology, however, evidence suggests HSP70 to have a more versatile range of functions, as genetic deletion of its inducible genes impairs Ca²⁺ handling, and consequently, cardiac and skeletal muscle contractility. Still, it is unknown whether HSP70 is involved in vascular reactivity, an intrinsic physiological mechanism of blood vessels. Therefore, we designed this study to test the hypothesis that proper vascular reactivity requires the assistance of HSP70.

Main methods

We performed functional studies in a wire-myograph using thoracic aorta isolated from male Sprague Dawley rats. Experiments were conducted with and without an HSP70 inhibitor as well as in heat-stressed vessels. The expression levels of HSP70 were evaluated with Western blotting. NO and ROS levels were assessed with fluorescence microscopy.

Key findings

We report that blockade of HSP70 weakens contraction in response to phenylephrine (dose-response) in the aorta. Additionally, we demonstrated that inhibition of HSP70 affects the amplitude of the fast and of the slow components of the time-force curve. Corroborating these findings, we found that inhibition of HSP70, in vessels over-expressing this protein, partly rescues the contractile phenotype of aortic rings. Furthermore, we show that blockade of HSP70 facilitates relaxation in response to acetylcholine and clonidine without affecting the basal levels of NO and ROS.

Significance

Our work introduces an additional physiological role for HSP70, the assistance of vascular reactivity, which highlights this protein as a new player in vascular physiology, and therefore, uncovers a promising research avenue for vascular diseases.

中文翻译：

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HSP70的其他生理作用：协助血管反应。

目的

HSP70，一种分子伴侣，有助于维持蛋白稳态。然而，在肌肉生物学中，证据表明HSP70具有更广泛的功能范围，因为其可诱导基因的基因缺失会损害Ca ^2+的处理能力，从而损害心脏和骨骼肌的收缩能力。但是，尚不清楚HSP70是否参与血管反应性，血管反应性是血管的内在生理机制。因此，我们设计了这项研究，以检验以下假设：适当的血管反应性需要HSP70的协助。

主要方法

我们使用从雄性Sprague Dawley大鼠中分离出的胸主动脉在钢丝肌电图仪中进行了功能研究。在有或没有HSP70抑制剂的情况下以及在热应力容器中进行了实验。用蛋白质印迹法评估HSP70的表达水平。用荧光显微镜评估NO和ROS水平。

主要发现

我们报告说，对HSP70的阻断减弱了对主动脉苯肾上腺素的剂量反应（剂量反应）。此外，我们证明了抑制HSP70会影响时间-力曲线的快速和慢速分量的幅度。为证实这些发现，我们发现在过表达该蛋白的血管中对HSP70的抑制可部分挽救主动脉环的收缩表型。此外，我们表明对HSP70的阻滞促进了对乙酰胆碱和可乐定的响应而不会影响NO和ROS的基础水平的放松。

意义

我们的工作引入了HSP70的另一种生理作用，即血管反应性的辅助，这突显了该蛋白作为血管生理学的新角色，因此，揭示了有希望的血管疾病研究途径。