Hypertension is a long-term condition that can increase organ susceptibility to insults and lead to severe complications such as chronic kidney disease (CKD). Extracellular vesicles (EVs) are cell-derived membrane structures that participate in cell-cell communication by exporting encapsulated molecules to target cells, regulating physiological and pathological processes. We here demonstrate that multiple administration of EVs from adipose-derived mesenchymal stromal cells (ASC-EVs) in deoxycorticosterone acetate (DOCA)-salt hypertensive model can protect renal tissue by maintaining its filtration capacity. Indeed, ASC-EVs downregulated the pro-inflammatory molecules monocyte chemoattracting protein-1 (MCP-1) and plasminogen activating inhibitor-1 (PAI1) and reduced recruitment of macrophages in the kidney. Moreover, ASC-EVs prevented cardiac tissue fibrosis and maintained blood pressure within normal levels, thus demonstrating their multiple favorable effects in different organs. By applying microRNA (miRNA) microarray profile of the kidney of DOCA-salt rats, we identified a selective miRNA signature associated with epithelial-mesenchymal transition (EMT). One of the key pathways found was the axis miR-200-TGF-β, that was significantly altered by EV administration, thereby affecting the EMT signaling and preventing renal inflammatory response and fibrosis development. Our results indicate that EVs can be a potent therapeutic tool for the treatment of hypertension-induced CKD in cardio-renal syndrome.

中文翻译：

---

脂肪间充质细胞衍生的电动汽车通过促进心脏-肾脏保护来减轻DOCA-盐诱导的高血压。

高血压是一种长期疾病，会增加器官对侮辱的敏感性，并导致严重的并发症，例如慢性肾脏病（CKD）。细胞外囊泡（EVs）是细胞衍生的膜结构，通过将包封的分子输出到靶细胞，调节生理和病理过程来参与细胞间通信。我们在这里证明，在醋酸脱氧肾上腺皮质激素（DOCA）-盐高血压模型中，多次施用源自脂肪的间充质基质细胞（ASC-EV）的EV可以通过维持其滤过能力来保护肾脏组织。实际上，ASC-EV下调了促炎分子单核细胞趋化蛋白1（MCP-1）和纤溶酶原激活抑制剂1（PAI1），并减少了巨噬细胞在肾脏中的募集。而且，ASC-EV预防了心脏组织纤维化，并将血压保持在正常水平，因此证明了它们在不同器官中的多种有利作用。通过应用DOCA-盐大鼠肾脏的microRNA（miRNA）芯片概况，我们确定了与上皮-间质转化（EMT）相关的选择性miRNA标记。发现的关键途径之一是轴miR-200-TGF-β，该轴可通过EV施用显着改变，从而影响EMT信号传导并防止肾炎性反应和纤维化的发展。我们的结果表明，电动汽车可以作为一种有效的治疗工具，用于治疗心肾综合征中由高血压引起的CKD。通过应用DOCA-盐大鼠肾脏的microRNA（miRNA）芯片概况，我们确定了与上皮-间质转化（EMT）相关的选择性miRNA标记。发现的关键途径之一是轴miR-200-TGF-β，该轴可通过EV施用显着改变，从而影响EMT信号传导并防止肾炎性反应和纤维化的发展。我们的结果表明，电动汽车可以作为一种有效的治疗工具，用于治疗心肾综合征中由高血压引起的CKD。通过应用DOCA-盐大鼠肾脏的microRNA（miRNA）芯片概况，我们确定了与上皮-间质转化（EMT）相关的选择性miRNA标记。发现的关键途径之一是轴miR-200-TGF-β，该轴可通过EV施用显着改变，从而影响EMT信号传导并防止肾炎性反应和纤维化的发展。我们的结果表明，电动汽车可以作为一种有效的治疗工具，用于治疗心肾综合征中由高血压引起的CKD。从而影响EMT信号传导并防止肾脏炎症反应和纤维化的发展。我们的结果表明，电动汽车可以作为一种有效的治疗工具，用于治疗心肾综合征中由高血压引起的CKD。从而影响EMT信号传导并防止肾脏炎症反应和纤维化的发展。我们的结果表明，电动汽车可以作为一种有效的治疗工具，用于治疗心肾综合征中由高血压引起的CKD。