Coronary Vasa Vasorum - Role of 3D Branching Geometry

这个更新的建议继续我们的探索vasa vasorum（微血管灌注的血管）。 动脉壁）中的冠状动脉疾病。长期目标是阐明溶质运移的作用 在动脉粥样硬化的开始和/或进展中穿过动脉壁。相关的网页资讯 对NHLBI的使命的认识是，它应该提供对可能的早期治疗的深入了解， 逆转关节硬化症，从而减少由晚期关节炎引起的主要公共卫生问题。 导致冠状动脉狭窄和心肌梗塞的动脉粥样硬化。 该提议旨在检验血管在以下方面发挥重要作用的总体假设： 由于动脉壁内溶质转运受到干扰而引发冠状动脉粥样硬化， 在细胞侵入和/或增殖之前。到目前为止，仅仅是瓦萨变化的关联问题， 血管壁（W）与早期动脉粥样硬化形成的关系已经得到我们的研究的肯定回答。什么 W在多大程度上实际上在启动过程中发挥了主要或促进作用，这一点仍有待确定。 或者仅仅是对这个过程做出反应。我们的方法主要基于使用 基于显微CT的成像方法，包括我们的新的、内部开发的、低温恒温显微CT方法， 还通过离体W收缩状态的体外表征。这将涉及冠状动脉的分析 在患有饮食诱导的高胆固醇血症或肾动脉狭窄（支架诱导的）动脉高血压的猪中， 两者都是动脉粥样硬化形成的危险因素。 目的I：探索单个W树的灌注领域，功能的位置，形状，大小和 洗入/洗出特性。这些区域的三维几何形状和溶质输运局部化函数 将成为了解动脉壁脂质积聚的基础。 目的II：利用冷冻微CT技术探讨血管内皮通透性在冠状动脉和冠状动脉中的作用 扫描。用微栓塞法使单个W在其起源处附近急性闭塞，以评估其能力。 W在灌注区域中连续，以补偿局部灌注损失。 目的III：在一些W的微栓塞慢性恢复后， 一方面冠状动脉壁灌注空洞的位置和大小， 另一方面，沉积物将是溶质转运改变的病理后果的直接测试。 W.这一建议的具体意义在于，如果W在 动脉粥样硬化的开始或进展，获得这种可能的治疗益处， 新的信息是，无论是刺激（或抑制，取决于我们的研究结果）的血管生成的W 可以延缓动脉粥样硬化的发作和/或严重程度。

This renewal proposal continues our exploration of the vasa vasorum (the microvessels perfusing the arterial wall) in coronary artery disease. The long-term objective is to clarify the role of solute transport across the arterial wall in the initiation and/or progression of atherosclerosis. The relevance of this knowledge to the mission of NHLBI is that it should provide insight into possible early treatments to arrest or reverse arthrosclerosis and thereby reduce major public health problems resulting from advanced atherosclerosis causing coronary artery stenosis and myocardial infarction. This proposal is designed to test the overall hypothesis that the vasa vasorum can play an important role in the initiation of coronary atherogenesis by virtue of disturbed solute transport within the arterial wall occurring prior to cellular invasion and/or proliferation. So far the question of mere association of changes in vasa vasorum (W) with early atherogenesis has already been answered in the affirmative by our studies. What remains to be determined is to what extent the W actually play a primary or facilitating role in the initiation of the artherosclerotic process or merely respond to that process. Our approach is based primarily on use of micro-CT-based imaging methods including our novel, in-house developed, cryostatic micro-CT method and also by in-vitro characterization of isolated W contractile state. This will involve analysis of coronary arteries of pigs with diet-induced hypercholesterolemia or renal artery stenosis (stent-induced) arterial hypertension, both being risk factors for atherogenesis. AIM I: Explore individual W trees' perfusion territories', function in terms of location, shape, size and washin/washout characteristics. The 3D geometry and solute transport localized function of these territories will form the basis for understanding of lipid accumulation in the arterial wall. AIM II: Explore the role of endothelial permeability in the W and coronary artery using cryostatic micro-CT scans. Use micro embolism to cause acute occlusion of single W near their origin to evaluate the ability of W contiguous in perfusion territories, to compensate for the localized loss of perfusion. AIM III: Following chronic recovery from micro-embolization of some of the W, the relationship between location and size of coronary arterial wall perfusion-voids on the one hand and histologically localized 'lipid1 deposits on the other will be a direct test of the pathological consequences of alterations in solute transport characteristics of W. The specific significance of this proposal is that if W play an important role in the initiation or progression of atherosclerosis, a possible therapeutic benefit that may result from acquiring this new information is that either stimulation (or inhibition; depending on our findings) of vasculogenesis of W could retard the onset and/or severity of atherosclerosis.