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Early detection and treatment strategies for vulnerable atherosclerotic plaques.

机译：脆弱动脉粥样硬化斑块的早期发现和治疗策略。

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摘要

Atherosclerotic plaque ruptures have been determined as the most common underlying cause of acute coronary syndromes and stroke. Currently, the standard of care for plaque rupture risk is based on the amount of luminal stenosis presented in a particular vessel; however, X-ray angiographic studies have shown that plaques at risk of rupture generally show <50% luminal narrowing. These findings explicate the need for other, more accurate methods of identifying problem lesions prior to the rupture event. Unfortunately, the study of thrombotic events and vulnerable plaque lesions in humans is difficult due to the spontaneity of rupture and the lengthy time course of disease progression. To further the understanding of plaque rupture risk in light of vulnerability detection, a rabbit model of atherothrombosis was used in conjunction with magnetic resonance imaging (MRI). MRI has been validated as a suitable imaging modality for in vivo, non-invasive detection of atherosclerosis and has provided quantitative predictors of plaques at risk of rupture. Additionally, the rabbit model has been shown, histologically, to present 6 of the 8 human plaque types classified by the American Heart Association.;The first portion of this dissertation work focuses on using MRI to serially image rabbits undergoing the atherosclerotic protocol in order to assess rupture risk at the various time points. Previous work has determined that an increase in the vessel remodeling ratio (which hides a large plaque in the vessel wall) and contrast uptake (which indicates inflammation) are both characteristics of increased rupture risk. By obtaining these parameters at various time points in the disease progression, it was possible to determine when a certain plaque displays a heightened risk of rupture. The second portion of this work tested the efficacy of a pro-resolving molecule, lipoxin (an endogenous molecule), in reducing atherosclerotic disease state, specifically rupture with a luminal thrombus. Using chronic administration of this molecule in the same rabbit model of atherosclerosis yielded a faint reduction in atherosclerotic severity based on the parameters of decreased vessel lipid content and decreased thrombotic events presented in the treated group.
机译：动脉粥样硬化斑块破裂已被确定为急性冠状动脉综合征和中风的最常见根本原因。当前，斑块破裂风险的护理标准是基于特定血管内腔狭窄的数量。但是，X射线血管造影研究表明，具有破裂风险的斑块通常显示<50％的管腔变窄。这些发现说明了在破裂事件发生之前需要其他更准确的方法来识别问题病灶的方法。不幸的是，由于破裂的自发性和疾病进展的漫长过程，很难对人的血栓形成事件和易损斑块病变进行研究。为了通过漏洞检测进一步了解斑块破裂风险，将兔动脉粥样硬化模型与磁共振成像（MRI）结合使用。 MRI已被证实是用于体内非侵入性动脉粥样硬化检测的一种合适的成像方式，并提供了具有破裂风险的斑块的定量预测指标。此外，从组织学上讲，该兔模型已显示出美国心脏协会（American Heart Association）分类的8种人类斑块类型中的6种。论文的第一部分着重于使用MRI对经历动脉粥样硬化协议的兔子进行连续成像，以便在各个时间点评估破裂风险。先前的工作已经确定，血管重塑率的增加（这在血管壁中隐藏了一块大斑块）和造影剂的摄取（表明炎症）都是破裂风险增加的特征。通过在疾病进展的各个时间点获得这些参数，可以确定某个斑块何时显示出更高的破裂风险。这项工作的第二部分测试了促分解分子脂蛋白（一种内源性分子）在减少动脉粥样硬化疾病状态，特别是腔内血栓破裂中的功效。根据治疗组中血管脂质含量降低和血栓形成事件减少的参数，在同一兔动脉粥样硬化模型中长期使用该分子可导致动脉粥样硬化严重程度的轻度降低。

著录项

  • 作者

    Pham, Tuan Anh.;

  • 作者单位

    Boston University.;

  • 授予单位 Boston University.;
  • 学科 Biophysics General.;Biology Physiology.;Engineering Biomedical.
  • 学位 Ph.D.
  • 年度 2015
  • 页码 210 p.
  • 总页数 210
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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