Coronary Vasa Vasorum - Role of 3D Branching Geometry

这一更新建议继续了我们对血管(微血管灌流)的探索 冠状动脉疾病中的动脉壁)。长期目标是阐明溶质运输的作用。 穿过动脉壁在动脉粥样硬化的启动和/或进展中。这件事的关联性 对NHLBI任务的了解是，它应该提供对可能的早期治疗的洞察，以逮捕或 逆转关节硬化症，从而减少由晚期 动脉粥样硬化导致冠状动脉狭窄和心肌梗死。 这一建议旨在检验血管在心脏疾病中发挥重要作用这一总体假设。 动脉壁内溶质运输紊乱引发冠状动脉粥样硬化 在细胞入侵和/或扩散之前。到目前为止，仅仅与血管的变化有关的问题 Vasorum(W)具有早期的动脉粥样硬化形成作用，我们的研究已经给出了肯定的答案。什么 有待确定的是，在多大程度上，W实际上在启动 动脉粥样硬化过程或仅仅对该过程有反应。我们的方法主要基于使用 基于Micro-CT的成像方法，包括我们自行开发的新型低温恒温Micro-CT方法和 也通过体外表征分离的W收缩状态。这将涉及对冠状动脉的分析 对于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， 两者都是动脉粥样硬化形成的危险因素。 目的I：从位置、形状、大小和大小等方面探索单个W树的“灌注区”、功能和功能 洗入/洗出特性。这些区域的三维几何和溶质运移的局域函数 将形成了解动脉壁脂积聚的基础。 目的II：应用低温静态显微CT技术探讨血管内皮细胞通透性在W动脉和冠状动脉中的作用 扫描。用微栓塞术造成单侧近端急性闭塞评价其治疗能力 在灌注区是连续的，以补偿局部的灌流损失。 目的III：慢性部分W期微栓塞术恢复后，两者之间的关系 冠状动脉壁灌注空洞的位置和大小与组织学定位的脂蛋白1 另一层上的沉积物将直接测试溶质运输变化的病理后果。 这项提议的具体意义在于，如果W在 动脉粥样硬化的开始或进展，这可能是获得这种疾病的治疗益处 新的信息是，无论是刺激(或抑制；取决于我们的发现)W的血管生成 可以延缓动脉粥样硬化的发生和/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.