Coronary Vasa Vasorum - Role of 3D Branching Geometry

描述(逐字摘自申请者摘要)：此重新提交 由三个重叠的目标按时间顺序组成，这些目标测试 全面的假设认为，血管在脑出血中起重要作用 冠状动脉粥样硬化的启动(即，在细胞入侵和/或 增殖)通过血管被扰乱的溶质运输 这又是由于血管远端血管的灌流压力所致。 管腔小于动脉壁内的压力。我们的方法是 定量地描述了详细的分支几何形状和溶质运移 冠状动脉的血管迷走神经，主要是利用基于显微CT的成像 方法：研究方法。这将包括对正常猪的冠状动脉进行分析， 猪(饮食诱导)高胆固醇血症模型和猪(肾)模型 动脉支架)模型(两者都是高血压的危险因素 动脉粥样硬化)。目标I是为了初步开发和集成 我们建议在整个提案中使用的各种技术，并建立 正常状态。AIM II将AIM I中的发展应用于 高胆固醇血症和高血压猪的冠脉壁 将血管对这些病理情况的反应联系起来。目标 III建立在AIM II的基础上，我们将结合高胆固醇血症和 高血压，看看它们是否是线性相加的效果， 根据我们的假设预测。主要目标是将运输与 血管容量对冠状动脉血管空间密度的影响 以及三维分支几何结构的流体动力学含义 血管内压应力的空间分布 冠状动脉壁。这项提议的意义在于，如果 这项研究的假设得到支持，它应该能洞察到几个 令人费解的观察。其一是动脉粥样硬化通常不会形成于 静脉(有血管)或小动脉(没有血管) 血管)。同样耐人寻味的是观察到早期动脉粥样硬化 不在外中膜或外膜形成，即使血管提供了 相当大的内皮表面(据推测也会变得功能失调) 外膜和外膜。另一种观察是，阿特宁的 外膜受到操纵，静脉受到动脉压力的影响。 或通过手术操作，确实会发展成动脉粥样硬化。

DESCRIPTION (Verbatim from the Applicant's Abstract): This resubmission consists of a chronological sequence of three overlapping aims which test the overall hypothesis that the vasa vasorum play an important role in the initiation of coronary atherogenesis (i.e., prior to cellular invasion and/or proliferation) by virtue of disturbed solute transport via the vasa vasorum This, in turn, is due to the perfusion pressure in their distal vasa vasorum lumens being less than the compression in the arterial wall. Our approach is to quantitatively describe detailed branching geometry and solute transport of the vasa vasorum of coronary arteries, primarily by use of micro-CT-based imaging methods. This will involve analysis of coronary arteries of normal pigs, a porcine (diet-induced) model of hypercholesterolemia and a porcine (renal artery stent) model of arterial hypertension (both being risk factors for atherogenesis). AIM I is for the initial development and integration of the various techniques we propose to use throughout the proposal and to establish the normal state. AIM II applies the developments in Aim I to hypercholesterlemic and to hypertensive pigs' coronary artery walls so as to relate the response of the vasa vasorum to these pathological conditions. AIM III builds on Aim II in that we will combine the hypercholesterolemia and hypertension to see if they are linearly additive in effect, as would be predicted by our hypothesis. The primary objective is to relate the transport capacity of vasa vasorum to the spatial density of coronary artery vasa vasorum and the fluid dynamic implications of both the 3D branching geometry of the vasa vasorum and the spatial distribution of compressive stresses within the coronary artenal wall. The significance of this proposal is that if the hypothesis of this study is supported, it should give insight into several puzzling observations. One is that atherosclerosis does not generally form in veins (which have vasa vasorum) or in small arteries (which have no vasa vasorum). Equally intriguing is the observation that early atherosclerosis does not form in the outer media or adventitia even though vasa vasorum provide a sizable endothelial surface (which presumably also becomes dysfunctional) in the outer media and adventitia. Another observation is that artenes whose adventitia are manipulated and veins, which are subjected to arterial pressure or surgically manipulated, do develop atherosclerosis.