Vascular mechanobioengineering

心血管疾病是社会的一个重要负担。动脉粥样硬化斑块早在儿童时期就已形成，全身性风险因素已被确定，沿着出现了潜在的预防和治疗途径。鉴于目前的流行病，努力的目标是通过生物标志物鉴定和分子成像开发进行诊断，并通过开发新分子进行治疗。** 动脉粥样硬化发展局灶性，并与内皮机械生物学。体外、离体和体内研究确定了动脉粥样硬化的标志，如炎症标志物的表达。动脉重塑通过基质金属蛋白酶及其抑制剂的作用改变血管壁几何形状以及细胞外基质组成/方向，并通过迁移、增殖和细胞凋亡改变细胞内容物，从而可能影响进展和结果。了解重塑对机械生物学的影响可以为早期检测和改善治疗提供新的靶点。** 将在体外检查炎症标志物和基质金属蛋白酶的调节。主要目的是（1）设计和验证体外机械刺激系统，（2）研究均匀几何结构支架中暴露于壁剪切应力或循环应变的内皮细胞的炎症反应，以及（3）表征模拟重塑动脉的支架中复杂机械刺激（血流动力学剪切和机械应变）下的内皮细胞反应。 开发的体外模型将为研究界提供机械生物学研究的工具，允许对其他细胞类型，药物制剂和其他病理背景进行测试。所确定的生物标志物将提供潜在的新药物疗法，对制药行业来说是有意义的，并且是正在开发的分子成像探针的目标。机械生物学研究将提供有关生物标志物的重要信息，最终导致预期寿命/质量的提高，并使个人受益，这反过来将对加拿大产生积极的社会和经济影响。

Cardiovascular diseases represent an important burden for society. Atherosclerotic plaques develop as early as childhood and systemic risk factors have been identified, along with potential preventative and therapeutic avenues. Given the current pandemic, efforts are targeted towards diagnosis, through biomarker identification and molecular imaging development, and treatment, by developing novel molecules. ** Atherosclerosis develops focally and is linked to endothelial mechanobiology. In vitro, ex vivo and in vivo studies identified hallmarks of atherosclerosis such as expression of inflammatory markers. Arterial remodelling alters vessel wall geometry, as well as extracellular matrix composition/orientation, through the action of matrix metalloproteinases and their inhibitors, and cellular content, through migration, proliferation and apoptosis, potentially affecting progression and outcome. Understanding the effects of remodelling on mechanobiology can provide novel targets for earlier detection and improved treatments. ** Regulation of inflammatory markers and matrix metalloproteinases will be examined in vitro. The main objectives are to (1) design and validate in vitro systems for mechanical stimulation, (2) study inflammatory response of endothelial cells exposed to wall shear stress or cyclic strain in uniform geometry scaffolds, and (3) characterize endothelial cell response under complex mechanical stimuli (both hemodynamic shear and mechanical strain) in scaffolds mimicking remodelled arteries.** The developed in vitro models will provide tools to the research community for mechanobiological studies, allowing tests on other cell types, pharmaceutical agents and in other pathological contexts. The biomarkers identified will provide potential new drug therapies, of interest to the pharmaceutical industry, and targets for molecular imaging probes that are being developed. Mechanobiological studies will provide crucial information on biomarkers, eventually leading to increased life expectancy/quality and benefiting individuals which in turn will have both a positive social and economic effect on Canada.******