期刊
INTERNATIONAL JOURNAL OF NANOMEDICINE
卷 6, 期 -, 页码 179-195出版社
DOVE MEDICAL PRESS LTD
DOI: 10.2147/IJN.S12760
关键词
endothelial cells; atomic force microscopy; cytokines; elastic modulus
资金
- Telemedicine and Advanced Technology Research Center (TATRC) of the US Army Medical Research Acquisition Activity (USAMRAA)
- NIH [U54CA143837]
- State of Texas, Emerging Technology Fund
- [DODW81XWH-09-1-0212]
- [W81XWH-07-2-0031]
- [81XWH-04-2-0067TexSHIELD]
- NATIONAL CANCER INSTITUTE [U54CA143837] Funding Source: NIH RePORTER
TNF-alpha (tumor necrosis factor-alpha) is a potent pro-inflammatory cytokine that regulates the permeability of blood and lymphatic vessels. The plasma concentration of TNF-alpha is elevated (> 1 pg/mL) in several pathologies, including rheumatoid arthritis, atherosclerosis, cancer, pre-eclampsia; in obese individuals; and in trauma patients. To test whether circulating TNF-alpha could induce similar alterations in different districts along the vascular system, three endothelial cell lines, namely HUVEC, HPMEC, and HCAEC, were characterized in terms of 1) mechanical properties, employing atomic force microscopy; 2) cytoskeletal organization, through fluorescence microscopy; and 3) membrane overexpression of adhesion molecules, employing ELISA and immunostaining. Upon stimulation with TNF-alpha (10 ng/mL for 20 h), for all three endothelial cells, the mechanical stiffness increased by about 50% with a mean apparent elastic modulus of E similar to 5 +/- 0.5 kPa (similar to 3.3 +/- 0.35 kPa for the control cells); the density of F-actin filaments increased in the apical and median planes; and the ICAM-1 receptors were overexpressed compared with controls. Collectively, these results demonstrate that sufficiently high levels of circulating TNF-alpha have similar effects on different endothelial districts, and provide additional information for unraveling the possible correlations between circulating pro-inflammatory cytokines and systemic vascular dysfunction.
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