| 摘要: | 研究期間：10108~10207;Background: According to WHO statistics, approximately 500 million people die of smoking-related diseases each year worldwide. In Taiwan, nowadays there are about 450 million smokers, and more than 18,000 people die each year due to smoking-related diseases, that means one is killed by cigarette smoking every 20 minutes. As compared with advanced countries, the number of Taiwanese male smoker is 1.5 and 1.8-fold higher than US and Canada, respectively, and the smoker age dramatically decreases over last decade. Therefore, tobacco can be foreseen as a top threat for public health. In addition to known pulmonary diseases, the chemicals generated by cigarette smoking can enter systemic circulation through capillaries, leading physiological lesions and/or complicated cardiovascular diseases. Although vascular disease is highly associated with smoking, the mechanisms by which cigarette smoking contributes to vascular disease are not completely understood as yet, because tobacco contain various constituents that will widely affect physiological systems including nervous, endocrine, metabolic, circulatory, and many other organs. Presently it has been demonstrated that the tobacco components do impact vascular endothelial cell (EC) growth. However, most of studies were conducted by assays with static cell culture, which can not truly reflect the interactions between ECs and cigarette smoking since (1) human vascular ECs are actually growing with blood flow-induced shear stress that plays a crucial role in regulating gene expression of ECs; (2) in blood vessel, the interactions between ECs and smooth muscle cells (SMCs) will be impacted by environment condition, hence dramatically affect EC performances accordingly. These interactions in response to surroundings should not be ignored when investigating the correlations between cigarette smoking and vascular lesions. Current research efforts still can not clearly present how the human vascular cells/tissues are adversely impacted by cigarette smoking due to above limitations. Method & Features: Among more than 4000 compounds in cigarette smoking, we will select the most important ingredient; nicotine, as the target chemical for study of smoking-induced vascular lesions. To overcome aforementioned inadequacies in the existing approaches, we will (1) apply laminar shear stress onto Human umbilical vein endothelial cells (HUVECs) surface to mimic the actual in vivo growing environment of ECs, and (2) evaluate how nicotine affects interactions between HUVECs and SMCs through various cellular & molecular assays. Results of this study will truly exhibit how the nicotine impacts vascular ECs, and could be further investigated for mechanism study and/or curing method development. Advantages: The principle investigator (PI; Y-H Lee) of the project has robust research background in the fields of bioengineering & cell/molecule biology, and has hands-on experience of experimental techniques for this project. The Co-PI, F-M Ho, is a cardiology physician and also a senior biomedical researcher who is with strong professions in clinical cardiovascular biology, being able to provide professional advice and hardware supports in this study. Hence this partnership is certainly qualified to conduct this research project. Specific Aims: The following tasks will be performed orderly in the next two years: The 1st Year 1. To assemble, set up, and test multi-components shear stress-generated laminar flow system. 2. To analyze how HUVECs react with shear stress in the presence of nicotine. 3. To evaluate nicotine-induced inflammation in HUVECs using blood cells adhesion test. The 2nd Year. Under the impact of shear stress: 1. To investigate molecular expressions of various atherosclerosis-related mRNA/proteins in nicotine-exposure HUVECs. 2. To study how the nicotine changes the interactions between HUVECs and SMCs. |
