Obesity-associated hypertension induces organ damage and it is important to identify the protein responsible for initiating organ damage involves a complex pathological mechanism which most likely consists of multiple players that alters the normal physiology. The present study focuses mainly on identifying the role of HMGB1 in cardiac and renal tissue damage following obesity-induced hypertension. Following high-fat diet and leptin injection, mice developed obesity-induced initial hypertension and critical hypertension after 4 and 9 months, respectively. Histology, Immunohistochemistry, Western blotting, and siRNA were used for analysis. Histopathological analysis showed that the compact nature of cardiac and renal tissues began to loosen at the initial stages of organ damage. At the advanced stages of organ damage, cardiac tissue hardened, and renal tissue exhibited fibrosis development. Immunohistochemistry and western blotting studies revealed that HMGB1 expression was elevated in cardiac and renal tissues following initial hypertension-induced organ damage, but its expression was downregulated at critical stages of organ damage. The inflammatory marker COX2 exhibited a gradually upregulated expression pattern as organ damage progressed. Silencing of HMGB1 expression after the development of initial organ damage significantly reduced COX2 expression, but its suppression at the advanced stage of organ damage was associated with increased COX2 expression. Our study shows that HMGB1 plays a key role in initiating organ damage following obesity-induced hypertension, and that once damage reaches a certain level, HMGB1 expression is downregulated.

中文翻译：

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撤回：在代谢综合征小鼠模型中，肥胖诱发的高血压导致器官损伤期间，HMGB1 和 COX2 受到调节。


肥胖相关的高血压会引起器官损伤，识别导致器官损伤的蛋白质非常重要，该蛋白质涉及复杂的病理机制，该机制很可能由改变正常生理机能的多个参与者组成。本研究主要集中于确定 HMGB1 在肥胖引起的高血压后心脏和肾组织损伤中的作用。在高脂饮食和注射瘦素后，小鼠分别在 4 个月和 9 个月后出现肥胖引起的初始高血压和严重高血压。使用组织学、免疫组织化学、蛋白质印迹和 siRNA 进行分析。组织病理学分析表明，心脏和肾组织的致密性质在器官损伤的初始阶段开始松弛。在器官损伤的晚期阶段，心脏组织硬化，肾组织出现纤维化发展。免疫组织化学和蛋白质印迹研究表明，在高血压引起的最初器官损伤后，心脏和肾脏组织中 HMGB1 表达升高，但在器官损伤的关键阶段其表达下调。随着器官损伤的进展，炎症标志物COX2表现出逐渐上调的表达模式。发生初始器官损伤后HMGB1表达的沉默显着降低了COX2的表达，但在器官损伤的晚期阶段其抑制与COX2表达的增加相关。我们的研究表明，HMGB1 在肥胖引起的高血压后引发器官损伤中起着关键作用，一旦损伤达到一定水平，HMGB1 表达就会下调。