title: Synergistic Impact of Nicotine and Shear Stress Induces Cytoskeleton Collapse and Apoptosis in Endothelial Cells.
abstract: Nicotine is the major component in cigarette smoke and has been recognized as a risk factor for various cardiovascular diseases such as atherosclerosis. However, the definite pathogenesis of nicotine-mediated endothelial dysfunction remains unclear because hemodynamic factor in most of prior in vitro studies was excluded. To understand how nicotine affects endothelium in the dynamic environment, human umbilical vein endothelial cells were treated by different laminar shear stresses (LSS; 0, 6, 8, and 12 dynes cm(-2)) with and without 10(-4) M nicotine for 12 h in a parallel plate flow system, following detections of cellular morphology and apoptotic level. Our results showed that cells sheared by 12 dynes cm(-2) LSS with nicotine excessively elongated and aligned with the flow direction, and exhibited significant apoptosis as compared to the groups with nicotine or LSS alone. We reasoned that the irregular morphological rearrangement and elevated apoptosis were resulted from the interruption of mechanostasis due to cytoskeletal collapse. Furthermore, all the impaired responses can be rescued by treatment with free radical scavenger ascorbic acid (10(-4) M), indicating oxidative stress was likely mediated with the impairments. In summary, our findings demonstrated an essential role of LSS in nicotine-mediated endothelial injury occurring in the physiological environment.
authors: Graduate Institute of Biomedical Engineering, National Central University, Taoyuan County, Taiwan, ROC.
authors: Yu-Hsiang
authors: YH
authors: Lee
authors: Ruei-Siang
authors: RS
authors: Chen
authors: Nen-Chung
authors: NC
authors: Chang
authors: Kueir-Rarn
authors: KR
authors: Lee
authors: Chien-Tsai
authors: CT
authors: Huang
authors: Yu-Ching
authors: YC
authors: Huang
authors: Feng-Ming
authors: FM
authors: Ho
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D003599:Cytoskeleton / Q000378:metabolism*; D006439:Hemodynamics; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D009538:Nicotine / Q000009:adverse effects / Q000494:pharmacology*; D033081:Shear Strength / Q000187:drug effects*
chemical_list: D009538:Nicotine