School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana Monroe, Monroe, LA, 71201, USA.
Biochimie. 2019 Oct;165:206-209. doi: 10.1016/j.biochi.2019.08.007. Epub 2019 Aug 9.
Ongoing efforts are oriented towards the development of novel therapeutic agents to repress lung hyperpermeability responses due to inflammation. The endothelial barrier dysfunction triggered by such events, may eventually lead to severe cardiovascular complications, such as the Acute Respiratory Distress Syndrome. Hsp90 inhibitors are anticancer compounds, associated with strong anti-inflammatory responses in the endothelium. Our latest observations in experimental models of Acute Lung Injury suggest that P53 orchestrates, at least in part, such activities. Remarkably, both Hsp90 inhibition and P53 induction are associated with the activation of the Unfolded Protein Response element. The purpose of the current manuscript, is to introduce the hypotheses that UPR induction protects the vasculature against inflammation.
目前的研究方向是开发新型治疗药物，以抑制炎症引起的肺高通透性反应。这些事件引发的内皮屏障功能障碍，最终可能导致严重的心血管并发症，如急性呼吸窘迫综合征。Hsp90 抑制剂是一种抗癌化合物，与内皮细胞的强烈抗炎反应有关。我们在急性肺损伤实验模型中的最新观察结果表明，P53 至少部分地协调了这种活动。值得注意的是，Hsp90 抑制和 P53 诱导都与未折叠蛋白反应元件的激活有关。本文的目的是提出假设，即 UPR 诱导可保护血管免受炎症的影响。
