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血管内皮细胞吞噬衰老红细胞促进内皮间充质转化

黄程淋, 沈伟利^*

上海市高血压研究所，上海 200025

摘要

血管内皮细胞作为非专职吞噬细胞参与清除衰老红细胞。本文旨在探讨吞噬衰老红细胞后血管内皮细胞的表型分化。采用血管紧张素II (angiotensin II, Ang II)微量渗透泵灌注建立高血压小鼠模型，分离红细胞，体外构建内皮细胞-红细胞吞噬模型，应用Mito-FerroGreen 和Liperfluo 荧光探针分别检测线粒体游离铁与脂质过氧化水平。运用定量蛋白质组学分析内皮细胞吞噬衰老红细胞前后差异性蛋白的表达。研究结果显示，随着血压的升高，与对照组相比，Ang II 组小鼠的红细胞表现出典型的衰老特征，包括红细胞的肿胀和棘形细胞的出现，同时整合素相关蛋白(integrin-associated protein, CD47)的表达显著下降。内皮细胞吞噬衰老红细胞后，线粒体中的游离铁和脂质过氧化水平显著升高。通过定量蛋白组学分析发现，内皮细胞中调节脂肪酸、碳水化合物代谢及间充质骨架相关蛋白的含量增加。此外，免疫蛋白印迹结果显示，血管内皮细胞钙黏蛋白(vascular endothelial cadherin, VE-cadherin) 和血小板- 内皮细胞黏附分子-1 (platelet endothelial cell adhesionmolecule-1, PECAM-1/CD31)的表达水平降低，而间充质标志物如α-平滑肌肌动蛋白(α-smooth muscle actin, α-SMA)和成纤维细胞特异性蛋白1 (fibroblast-specific protein 1, FSP-1)的表达显著增加。上述结果提示，Ang II通过加快红细胞衰老，诱导内皮细胞吞噬衰老红细胞，从而促进内皮细胞向间充质细胞转化。

关键词： 噬红细胞; 内皮细胞; 衰老红细胞; 内皮间充质转化

Engulfment of senescent erythrocytes by endothelial cells promotes endothelial-to-mesenchymal transition

HUANG Cheng-Lin, SHEN Wei-Li^*

Shanghai Institute of Hypertension, Shanghai 200025, China

Abstract

Endothelial cells, as non-professional phagocytes, play a role in clearing senescent red blood cells (RBCs). This study explores the phenotypic differentiation of endothelial cells following the phagocytosis of senescent RBCs. A hypertensive mouse model was established via implantation of an angiotensin II (Ang II) micro-osmotic pump. RBCs were isolated from these mice, and an in vitro endothelial cell-RBC phagocytosis model was developed. Mito-FerroGreen and Liperfluo fluorescent probes were employed to measure mitochondrial free iron and lipid peroxidation levels, respectively. Quantitative proteomics analyzed the expression of differentially expressed proteins in endothelial cells before and after phagocytosing senescent RBCs. Results showed that, with increasing blood pressure, RBCs from the Ang II group exhibited typical aging characteristics compared to the control group, including swelling and the appearance of echinocytes, along with a significant decrease in the expression of integrin-associated protein (CD47). Following phagocytosis of senescent RBCs, endothelial cells exhibited increased mitochondrial free iron and lipid peroxidation. Quantitative proteomics analysis revealed upregulation of proteins involved in fatty acid, carbohydrate metabolism, and mesenchymal cytoskeleton in endothelial cells. Moreover, immunoblotting results showed decreased expression levels of vascular endothelial cadherin (VE-cadherin) and platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31), while mesenchymal markers such as α- smooth muscle actin (α-SMA) and fibroblast-specific protein 1 (FSP-1) were significantly upregulated. These findings suggest that Ang II-induced RBC senescence promotes their phagocytosis by endothelial cells, which in turn facilitates the transition of endothelial cells into mesenchymal cells.

Key words: erythrophagocytosis; endothelial cells; senescent red blood cells; endothelial-to-mesenchymal transition

收稿日期：　　录用日期：

通讯作者：沈伟利　　E-mail:

DOI: 10.13294/j.aps.2025.0057

引用本文：

黄程淋, 沈伟利. 血管内皮细胞吞噬衰老红细胞促进内皮间充质转化[J]. 生理学报 2025; 77 (6): 1123-1132.

HUANG Cheng-Lin, SHEN Wei-Li. Engulfment of senescent erythrocytes by endothelial cells promotes endothelial-to-mesenchymal transition. Acta Physiol Sin 2025; 77 (6): 1123-1132 (in Chinese with English abstract).