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首页> 外文学位 >Gender differences in rodent experimental abdominal aortic aneurysm development: Focusing on gonadal hormone regulation, chemokine and cytokine expression, leukocyte recruitment, matrix metalloproteinase activity, extracellular matrix protein degradation and synthesis, and treatment using a dendrimer-based system.
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Gender differences in rodent experimental abdominal aortic aneurysm development: Focusing on gonadal hormone regulation, chemokine and cytokine expression, leukocyte recruitment, matrix metalloproteinase activity, extracellular matrix protein degradation and synthesis, and treatment using a dendrimer-based system.

机译：啮齿动物实验性腹主动脉瘤发展中的性别差异：侧重于性腺激素调节，趋化因子和细胞因子表达，白细胞募集，基质金属蛋白酶活性，细胞外基质蛋白降解和合成以及使用基于树状聚合物的系统进行治疗。

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摘要

Abdominal aortic aneurysms (AAAs) are one of the leading causes of death in the United States each year. Although many patients require elective or emergent surgical repair of AAAs, there are presently no effective medical therapies to treat patients with AAAs. Epidemiological studies have shown that males form AAAs four times more often than females. The mechanical and molecular mechanisms behind this observation are unknown.; The present study hypothesizes that gender-related differences in aortic aneurysm formation are driven by hormonal regulation of the inflammatory response in the aortic wall, and it is the balance between extracellular matrix (ECM) proteins and enzymes that degrade them, namely matrix metalloproteinases (MMPs) that is critical. Although it is clear that aortic elastin concentration is markedly reduced through a loss of the internal elastic lamellae and other elastin components of the aortic media in AAAs, it is debated whether the collagen concentration in AAAs is decreased, unchanged, or increased, compared to normal aortic tissue.; Initially, gender-based differences in aortic tensile strength, ECM proteins, and MMPs between native male and female rats were examined to determine if inherent differences in mechanical properties, proteins, enzymes, and/or hormone levels favor the formation of aneurysms in males compared to females. Following experiments on aorta, the second aim involved the induction of an experimental AAA in a rodent model in which alterations in tensile strength, ECM proteins, and MMPs were tracked in control (salinetreated) and aneurysmal (elastase-treated) aortas of male and female rats. Additionally, the effects of hormonal and surgical gender manipulations on AAA formation and leukocyte recruitment were investigated, to provide insight into the reasons males are more susceptible to AAA formation compared to females.; Upon completion of these experiments, potential therapeutic agents which inhibit or slow the growth of experimental aneurysms in male rodents were selected. Finally, using experimental approaches, a drug delivery vehicle was developed to target tissue in normal and aneurysmal aortas. In conjunction with these experiments, the transport of these nano-scale dendrimers through aortic tissue was modeled theoretically.
机译：腹主动脉瘤（AAAs）是美国每年的主要死亡原因之一。尽管许多患者需要进行AAA的选择性或紧急手术修复，但目前尚无有效的药物疗法可治疗AAA的患者。流行病学研究表明，男性形成AAA的频率是女性的四倍。这种观察背后的机械和分子机制尚不清楚。本研究假设主动脉瘤形成中与性别相关的差异是由激素对主动脉壁炎症反应的调节驱动的，而正是细胞外基质（ECM）蛋白和降解它们的酶（即基质金属蛋白酶（MMPs））之间的平衡）至关重要。尽管很明显，由于AAA中主动脉介质的内部弹性薄片和其他弹性蛋白成分的损失，主动脉弹性蛋白浓度显着降低，但仍存在争议，与正常水平相比，AAA中的胶原蛋白浓度是降低，不变还是增加主动脉组织。最初，检查雄性和雌性大鼠之间基于性别的主动脉抗张强度，ECM蛋白和MMP的差异，以确定机械性能，蛋白质，酶和/或激素水平的内在差异是否有利于雄性动脉瘤的形成。对女性。在主动脉上进行实验之后，第二个目标涉及在啮齿动物模型中诱导实验性AAA，在该模型中，在雄性和雌性的对照（盐水处理）和动脉瘤（弹性蛋白酶处理）主动脉中追踪拉伸强度，ECM蛋白和MMP的变化大鼠。此外，还研究了激素和手术性别操纵对AAA形成和白细胞募集的影响，以洞悉男性比女性更容易AAA形成的原因。在完成这些实验后，选择了抑制或减慢雄性啮齿动物实验动脉瘤生长的潜在治疗剂。最后，使用实验方法，开发了一种药物递送媒介物，以靶向正常和动脉瘤主动脉中的组织。结合这些实验，理论上模拟了这些纳米级树状聚合物通过主动脉组织的运输。

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  • 作者

    Cho, Brenda S.;

  • 作者单位

    University of Michigan.;

  • 授予单位 University of Michigan.;
  • 学科 Engineering Biomedical.
  • 学位 Ph.D.
  • 年度 2006
  • 页码 173 p.
  • 总页数 173
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 生物医学工程;
  • 关键词

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