■动脉粥样硬化受内皮细胞活化和功能障碍的显著影响。研究表明,动脉粥样硬化斑块内纤连蛋白(Fn)的大量存在,促进内皮炎症和激活。然而,由各种细胞类型分泌的细胞Fn(cfn),包括内皮细胞和平滑肌细胞,和由肝细胞产生的血浆Fn(pFn)。它们是结构和功能都不同的Fn的不同形式。不同类型的Fn在促进内皮细胞活化和功能障碍中的具体作用仍不确定。因此,本研究旨在探讨pFn和内皮细胞来源的Fn(FnEC)在促进内皮细胞活化和功能障碍中的作用。
■最初,通过将细胞暴露于氧化低密度脂蛋白(ox-LDL)诱导内皮细胞损伤,随后我们产生了Fn敲低的主动脉内皮细胞突变株(FnEC-KD).FnEC-KD加入pFn对炎症因子表达水平的影响,血管收缩剂,和舒张因子进行比较。
■结果表明,FnEC-KD显着抑制ox-LDL诱导的细胞间粘附分子1(ICAM-1,p<0.05),血管细胞粘附分子(VCAM-1,p<0.05),内皮素(p<0.05)表达,和核因子κB(NFκB,p<0.05)激活。这些结果表明FnEC-KD抑制内皮细胞活化和功能障碍。令人惊讶的是,pFn的添加显著抑制ox-LDL诱导的ICAM-1(p<0.05),VCAM-1(p<0.05),内皮素(p<0.05)表达和NFκB(p<0.05)活化。暗示pFn抑制内皮细胞活化和功能障碍。此外,这项研究表明,ox-LDL刺激增加了过量一氧化氮的产生,导致严重的内皮细胞损伤。
■主动脉FnEC促进内皮细胞活化和内皮功能障碍,而pFn抑制ox-LDL诱导的内皮细胞活化和内皮功能障碍。
UNASSIGNED: Atherosclerosis is significantly influenced by endothelial cell activation and dysfunction. Studies have demonstrated the substantial presence of
fibronectin (Fn) within atherosclerotic plaques, promoting endothelial inflammation and activation. However, cellular Fn (cFn) secreted by various cell types, including endothelial cells and smooth muscle cells, and plasma Fn (pFn) produced by hepatocytes. They are distinct forms of Fn that differ in both structure and function. The specific contribution of different types of Fn in promoting endothelial cell activation and dysfunction remain uncertain. Therefore, this study aimed to investigate the respective roles of pFn and endothelial cell-derived Fn (FnEC) in promoting endothelial cell activation and dysfunction.
UNASSIGNED: Initially, endothelial cell injury was induced by exposing the cells to oxidized low-density lipoprotein (ox-LDL) and subsequently we generated a mutant strain of aortic endothelial cells with Fn knockdown (FnEC-KD). The impact of the FnEC-KD arel the addition of pFn on the expression levels of inflammatory factors, vasoconstrictors, and diastolic factors were compared.
UNASSIGNED: The results showed that the FnEC-KD significantly inhibited ox-LDL-induced intercellular adhesion molecule 1 (ICAM-1, p < 0.05), vascular cell adhesion molecule (VCAM-1, p < 0.05), and endothelin (p < 0.05) expression, and nuclear factor kappa-B (NFκB, p < 0.05) activation. These results implied that FnEC-KD inhibited both endothelial cell activation and dysfunction. Surprisingly, the addition of pFn significantly inhibited the ox-LDL-induced ICAM-1 (p < 0.05), VCAM-1 (p < 0.05), and endothelin (p < 0.05) expression and NFκB (p < 0.05) activation. Implying that pFn inhibits endothelial cell activation and dysfunction. Additionally, the study revealed that ox-LDL stimulation enhanced the production of excessive nitric oxide, leading to severe endothelial cell damage.
UNASSIGNED: Aortic FnEC promotes endothelial cell activation and endothelial dysfunction, whereas pFn inhibits ox-LDL-induced endothelial cell activation and endothelial dysfunction.