title: Topological control of nitric oxide secretion by tantalum oxide nanodot arrays.
abstract: 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, NFκB(p65), eNOS], but less associated with Inducible nitric oxide synthase (iNOS) pathway (TNF-α, ILK, Akt, IκBα, NFκB, iNOS). Western blotting of Akt, eNOS, iNOS, and NFκB 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.
authors.affiliation: Department Material Science and Technology, National Chiao Tung University Hsinchu, 1001 University Road, Hsinchu, 300, Taiwan, ROC. udeshdhawan.91@gmail.com.
authors.forename: Udesh
authors.initials: U
authors.lastname: Dhawan
authors.affiliation: Department Material Science and Technology, National Chiao Tung University Hsinchu, 1001 University Road, Hsinchu, 300, Taiwan, ROC. glitteringlover@gmail.com.
authors.forename: Chia Hui
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Department Material Science and Technology, National Chiao Tung University Hsinchu, 1001 University Road, Hsinchu, 300, Taiwan, ROC. ud.enliven@gmail.com.
authors.forename: Chun-Chung
authors.initials: CC
authors.lastname: Huang
authors.affiliation: Department Material Science and Technology, National Chiao Tung University Hsinchu, 1001 University Road, Hsinchu, 300, Taiwan, ROC. yinghaochu@gmail.com.
authors.forename: Ying Hao
authors.initials: YH
authors.lastname: Chu
authors.affiliation: Hokan Life Technology, F2, 793 Fu-Ke Road, Taichung, Taiwan, ROC. gstevehuang@gmail.com.
authors.forename: Guewha S
authors.initials: GS
authors.lastname: Huang
authors.affiliation: Department of Emergency Medicine, Changhua Christian Hospital, 135 Nanshiao Street, Changhua, 500, Taiwan. h6213.lac@gmail.com.
authors.forename: Yan-Ren
authors.initials: YR
authors.lastname: Lin
authors.affiliation: Department of Biological Science and Technology, National Chiao Tung University Hsinchu, 1001 University Road, Hsinchu, 300, Taiwan, ROC. wenurea@yahoo.com.tw.
authors.forename: Wen-Liang
authors.initials: WL
authors.lastname: Chen
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D004566:Electrodes; D005786:Gene Expression Regulation; D053758:Nanoparticles / Q000737:chemistry*; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D010087:Oxides / Q000737:chemistry*; D010316:Particle Size; D016133:Polymerase Chain Reaction; D051381:Rats; D013635:Tantalum / Q000737:chemistry*; D013997:Time Factors
chemical_list: D010087:Oxides; D009569:Nitric Oxide; D013635:Tantalum; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C078151:tantalum oxide