Regulation of matrix metalloproteinases in angiogenesis

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（如糖尿病）中受到损害。有效地控制血管生长（也称为血管生成）需要对生长过程的复杂性有透彻的了解，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）在骨骼肌血管生成的起始过程中起着不可或缺的作用，通过选择性地切割血管周围的网状基质，使新血管发芽。我们现在研究在血管发芽过程中这些MMPs是如何被控制的。在本提案中，我们将确定一些可以增加可用MMPs数量的关键刺激，以及这些刺激如何指导发芽血管尖端的MMPs组织，从而在发芽尖端前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，以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。

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.