Coronary Vasa Vasorum - Role of 3D Branching Geometry

描述（逐字摘自申请人摘要）：本次重新提交 由三个相互重叠的目标按时间顺序排列组成， 总的假设是，血管在 冠状动脉粥样硬化形成的开始（即，在细胞侵入之前和/或 增殖）通过经血管的溶质转运紊乱 这反过来又是由于他们远端血管的灌注压 管腔小于动脉壁中的压缩。我们的做法是 定量描述详细的分支几何形状和溶质运输的 冠状动脉的血管，主要通过使用基于微CT的成像 方法.这将涉及正常猪的冠状动脉分析， 猪（饮食诱导）高胆固醇血症模型和猪（肾） 动脉支架）模型的动脉高血压（两者都是风险因素， 动脉粥样硬化）。AIM I是用于初始开发和整合 我们建议在整个提案中使用的各种技术， 正常状态。目标二将目标一的发展应用于 高胆固醇血症和高血压猪的冠状动脉壁， 将血管的反应与这些病理状况联系起来。目的 III建立在目标II的基础上，我们将联合收割机结合高胆固醇血症和 高血压，看看他们是否是线性相加的效果，因为将 根据我们的假设。主要目标是将运输 血管容积对冠状动脉血管空间密度的影响 和流体动力学的影响，这两个三维分支几何形状的 血管内压应力的空间分布 冠状动脉壁这项建议的意义在于，如果 这项研究的假设是支持的，它应该提供洞察几个 令人困惑的观察一个是动脉粥样硬化通常不会在 静脉（有血管）或小动脉（无血管） vasorum）。同样有趣的是早期动脉粥样硬化的观察结果， 即使血管壁提供了一个 相当大的内皮表面（推测也变得功能障碍）， 外中膜和外膜。另一个观察是， 外膜被操纵，静脉受到动脉压力 或手术操作，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.