Li Yukun, Gao Anbo, Zhou Wenchao, Tang Xing, Zeng Tian, Fan Tingyu, Jiang Weimin, Tang Min, Ouyang Fan
Department of Assisted Reproductive Centre, Zhuzhou Central Hospital, Xiangya Hospital Zhuzhou Central South University, Central South University, Zhuzhou, Hunan, China.
Department of Cardiology, Xiangya Hospital Zhuzhou, Zhuzhou Central Hospital, Central South University, Central South University, Zhuzhou, Hunan, China.
Sci Rep. 2025 May 4;15(1):15572. doi: 10.1038/s41598-025-00581-7.
Palmitic acid (PA), being the most prevalent free fatty acid in the human, holds significant implications as a risk factor for atherosclerosis (AS) due to its ability to induce physiological dysfunction in endothelial cells (ECs). Endothelial cell-specific molecule 1 (ESM1), has been identified as a marker for activated ECs. Nevertheless, the mechanisms underlying ESM1-induced endothelial cell proliferation remain elusive. The expression of ESM1, ANGPTL4 and autophagy related protein were confirmed by western blot. Proliferation ability was tested by MTT and EdU. Lipids level was confirmed by Oil red staining. Autophagic flux was confirmed by Monodansylcadaverine (MDC) staining and pCMV-mCherry-GFP-LC3B fluorescence staining assay. The mouse model of AS was used to observe the effect of PA on the ESM1-ANGPTL4-autophagy signaling axis. This study elucidates ESM1-ANGPTL4 axis in maintaining proliferation of ECs and lipid reprogramming. Furthermore, it has been observed that PA has the ability to stimulate EC to autonomously increase the expression of ESM1, which in turn can counteract the detrimental effects of PA on ECs. Conversely, when ESM1 is suppressed, the damaging effects of PA on ECs are exacerbated. Mechanistically, our findings indicate that ESM1 facilitates EC proliferation and lipids homeostasis by up-regulating autophagy through ANGPTL4. This effect of ESM1 on ECs can be attenuated by ATG7 inhibiting. Additionally, the serum levels of ESM1 were found to be elevated in AS mice. ESM1 was found to enhance ECs proliferation and mitigate endothelial cell injury induced by PA through the upregulation of autophagy. This mechanism potentially serves as a protective factor against atherosclerosis progression.
棕榈酸（PA）是人体内最普遍的游离脂肪酸，因其能够诱导内皮细胞（ECs）发生生理功能障碍，而作为动脉粥样硬化（AS）的一个风险因素具有重要意义。内皮细胞特异性分子1（ESM1）已被确定为活化内皮细胞的标志物。然而，ESM1诱导内皮细胞增殖的潜在机制仍不清楚。通过蛋白质免疫印迹法证实了ESM1、血管生成素样蛋白4（ANGPTL4）和自噬相关蛋白的表达。通过MTT法和5-乙炔基-2'-脱氧尿苷（EdU）检测法检测增殖能力。通过油红染色确认脂质水平。通过单丹磺酰尸胺（MDC）染色和pCMV-红色荧光蛋白-绿色荧光蛋白-微管相关蛋白1轻链3β（pCMV-mCherry-GFP-LC3B）荧光染色法确认自噬通量。利用AS小鼠模型观察PA对ESM1-ANGPTL4-自噬信号轴的影响。本研究阐明了ESM1-ANGPTL4轴在维持内皮细胞增殖和脂质重编程中的作用。此外，研究发现PA能够刺激内皮细胞自主增加ESM1的表达，这反过来又可以抵消PA对内皮细胞的有害影响。相反，当ESM1受到抑制时，PA对内皮细胞的损伤作用会加剧。从机制上讲，我们的研究结果表明，ESM1通过ANGPTL4上调自噬来促进内皮细胞增殖和脂质稳态。ESM1对内皮细胞的这种作用可被自噬相关蛋白7（ATG7）抑制所减弱。此外，发现AS小鼠血清中ESM1水平升高。发现ESM1通过上调自噬来增强内皮细胞增殖并减轻PA诱导的内皮细胞损伤。这一机制可能是预防动脉粥样硬化进展的保护因素。
