Regulation of matrix metalloproteinases in angiogenesis

血管生成中基质金属蛋白酶的调节

• 批准号: 222865-2008
• 负责人: Haas, Tara
• 金额: $ 2.91万
• 依托单位: York University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2012
• 资助国家: 加拿大
• 起止时间: 2012-01-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=504204
• 关键词: Regulation; matrix; metalloproteinases; angiogenesis

The major goal of the research performed in my laboratory is to discover novel strategies for controlling blood vessel formation in skeletal muscle. Growth of new blood vessels is a necessary physiological response that is compromised in some disease states, such as diabetes. Efficient manipulation of blood vessel growth (also called angiogenesis) requires a thorough understanding of the intricacies of the growth process in order to select appropriate and effective therapeutic targets. My research group has demonstrated that matrix metalloproteinases (MMPs) play an integral role in the initiation of angiogenesis in skeletal muscle by selectively cutting the mesh-like matrix that surrounds blood vessels, enabling new blood vessels to sprout. We now study the ways in which these MMPs are controlled during the process of blood vessel sprouting. In this proposal, we will determine some of the key stimuli that can increase the amount of MMPs available, and how these stimuli direct the organization of MMPs at the tips of sprouting blood vessels, thus provides focused cutting of the matrix immediately in front of the sprouting tip. The findings from my research will provide building blocks for the future successful development of new strategies for controlling blood vessel growth in individuals lacking sufficient blood supply to their skeletal muscle, improving quality of life and decreasing health costs.

在我的实验室进行的研究的主要目标是发现控制骨骼肌血管形成的新策略。 新血管的生长是一种必要的生理反应，在某些疾病状态下会受到损害，例如糖尿病。 有效操纵血管生长（也称为血管生成）需要彻底了解生长过程的复杂性，以便选择适当和有效的治疗靶点。 我的研究小组已经证明，基质金属蛋白酶（MMPs）通过选择性切割血管周围的网状基质，使新血管发芽，在骨骼肌血管生成的启动中发挥着不可或缺的作用。 我们现在研究这些MMPs在血管发芽过程中的控制方式。 在这个提议中，我们将确定一些可以增加MMPs可用量的关键刺激，以及这些刺激如何指导MMPs在萌芽血管尖端的组织，从而在萌芽尖端前方立即提供基质的集中切割。 我的研究结果将为未来成功开发新的策略提供基础，这些策略用于控制骨骼肌缺乏足够血液供应的个体的血管生长，提高生活质量并降低健康成本。