DataSheet_3_The Role of AIF-1 in the Aldosterone-Induced Vascular Calcification Related to Chronic Kidney Disease: Evidence From Mice Model and Cell Co-Culture Model.pdf

Increasing evidence suggests that aldosterone (Aldo) plays an essential role in vascular calcification which is a serious threat to cardiovascular disease (CVD) developed from chronic kidney disease (CKD). However, the exact pathogenesis of vascular calcification is still unclear. First, we established CKD-associated vascular calcification mice model and knockout mice model to investigate the causal relationship between allograft inflammatory factor 1 (AIF-1) and vascular calcification. Then, endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) co-culture experiments were performed to further explore the mechanisms of calcification. The results of the Aldo intervention mice model and transgenic mice model showed that Aldo could cause calcification by increasing the AIF-1 level. The results of in vitro co-culture model of ECs and VSMCs showed that AIF-1 silence in ECs may alleviate Aldo-induced calcification of VSMCs. In conclusion, our study indicated that Aldo may induce vascular calcification related to chronic renal failure via the AIF-1 pathway which may provide a potential therapeutic target.

越来越多的证据表明，醛固酮（aldosterone, Aldo）在血管钙化过程中发挥关键作用，而血管钙化是慢性肾脏病（chronic kidney disease, CKD）继发心血管疾病（cardiovascular disease, CVD）的严重威胁。然而，血管钙化的确切发病机制仍未明确。本研究首先构建了CKD相关血管钙化小鼠模型与基因敲除小鼠模型，以探究同种移植炎症因子1（allograft inflammatory factor 1, AIF-1）与血管钙化之间的因果关联。随后，通过内皮细胞（endothelial cells, ECs）与血管平滑肌细胞（vascular smooth muscle cells, VSMCs）的共培养实验，进一步探讨血管钙化的潜在分子机制。醛固酮干预小鼠模型与转基因小鼠模型的实验结果显示，醛固酮可通过上调同种移植炎症因子1的表达水平诱导血管钙化。内皮细胞与血管平滑肌细胞体外共培养模型的结果表明，在内皮细胞中沉默同种移植炎症因子1的表达，可缓解醛固酮诱导的血管平滑肌细胞钙化。综上，本研究表明醛固酮可能通过同种移植炎症因子1通路，诱发与慢性肾功能衰竭相关的血管钙化，该发现可为相关疾病的治疗提供潜在靶点。