標題: Topological control of nitric oxide secretion by tantalum oxide nanodot arrays
作者: Dhawan, Udesh
Lee, Chia Hui
Huang, Chun-Chung
Chu, Ying Hao
Huang, Guewha S.
Lin, Yan-Ren
Chen, Wen-Liang
材料科學與工程學系
生物科技學系
Department of Materials Science and Engineering
Department of Biological Science and Technology
關鍵字: Tantalum oxide;Nanodots;Cardiomyocytes;eNOS;iNOS;Signaling pathway
公開日期: 9-十一月-2015
摘要: Background: Nitric oxide (NO) plays a very important role in the cardiovascular system as a major secondary messenger in signaling pathway. Its concentration regulates most of the important physiological indexes including the systemic blood pressure, blood flow, regional vascular tone and other cardiac functions. The effect of nanotopography on the NO secretion in cardiomyocytes has not been elucidated before. In this study, we report how the nanotopography can modulate the secretion profile of NO and attempt to elucidate the genetic pathways responsible for the same by using Tantalum Oxide nanodot arrays ranging from 10 to 200 nm. A series of nanodot arrays were fabricated with dot diameter ranging from 10 to 200 nm. Temporal NO release of cardiomyocytes was quantified when grown on different surfaces. Quantitative RT-PCR and Western blot were performed to verify the genetic pathways of NO release. Results: After hours 24 of cell seeding, NO release was slowly enhanced by the increase of dot diameter from 10 nm up to 50 nm, mildly enhanced to a medium level at 100 nm, and increase rapidly to a high level at 200 nm. The temporal enhancement of NO release dropped dramatically on day 3. On day 5, a topology-dependent profile was established that maximized at 50 nm and dropped to control level at 200 nm. The NO releasing profile was closely associated with the expression patterns of genes associated with Endothelial nitric oxide synthase (eNOS) pathway [GPCR, PI3K, Akt, Bad, Bcl-2, NF kappa B(p65), eNOS], but less associated with Inducible nitric oxide synthase (iNOS) pathway (TNF-alpha, ILK, Akt, I kappa Ba, NF kappa B, iNOS). Western blotting of Akt, eNOS, iNOS, and NF kappa B further validated that eNOS pathway was modulated by nanotopology. Conclusions: Based on the findings of the present study, 50, 100 nm can serve as the suitable nanotopography patterns for cardiac implant surface design. These two nanodot arrays promote NO secretion and can also promote the vascular smooth muscle relaxation. The results of this study can improve the heart stent design in the medical treatments.
URI: http://dx.doi.org/10.1186/s12951-015-0144-y
http://hdl.handle.net/11536/128373
ISSN: 1477-3155
DOI: 10.1186/s12951-015-0144-y
期刊: JOURNAL OF NANOBIOTECHNOLOGY
Volume: 13
起始頁: 0
結束頁: 0
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