Role of Birth on Microvasculature Development in Striated MuscleRole of Birth on Microvasculature Development in Striated Muscle

心脏和骨骼肌是类似类型的肌肉，当它们没有通过毛细血管灌注足够的血液时，它们会遇到类似的问题，包括收缩功能差，胰岛素抵抗和萎缩。心脏和骨骼肌的小血管或微血管在发育过程中的生长方式已被证明会影响这些问题的终身弹性或风险。出生代表了已知影响微血管生长和发育的因素的巨大变化，包括心脏和骨骼肌工作负荷的变化，以及随着肺取代胎盘，动脉血的氧合急剧增加。众所周知，出生后微血管系统会发生发育变化，但出生本身对微血管发育和编程的作用尚不清楚。在这项研究中，我们将使用一个大型动物模型（绵羊）来检查出生前后心脏和骨骼肌微血管的功能变化，以及功能差异背后的解剖学变化，以及驱动适应的分子信号。重要性：微血管生长对子宫内条件有反应，已知发育条件会影响心脏和心脏代谢疾病的终身恢复力和风险。出生是发育过程中的一个重要转折点，在这个转折点上，已知影响微血管生长的因素，包括肌肉工作负荷和动脉血氧水平，会急剧增加。我们的目标是了解出生如何改变微血管发育，以便找到改善心脏微血管疾病和心脏代谢健康的终身弹性的方法。

The heart and the skeletal muscle are similar types of muscle, and when they are not perfused with enough blood through their capillaries, they experience similar problems, including poor contractile function, resistance to insulin, and atrophy. How the small blood vessels, or microvasculature, of the heart and skeletal muscle grows during development has been shown to affect lifelong resilience or risk of these problems. Birth represents a big change in factors known to influence growth and development of the microvasculature, including changes in the workload of both the heart and skeletal muscle, and the oxygenation of the arterial blood increases dramatically as lungs replace placenta. It is known that there are developmental changes in the microvasculature after birth, but the role of birth itself on microvascular development and programming is unknown. In this study, we will use a large animal model (sheep) to examine functional changes in the microvasculature of heart and skeletal muscle before and after birth, as well as the anatomical changes underlying functional differences, and the molecular signals driving the adaptations. Significance: Microvascular growth is responsive to intrauterine conditions, and developmental conditions are known to affect lifelong resilience and risk for cardiac and cardiometabolic disease. Birth is a major transition point in development in which factors known to influence microvascular growth, including muscle workload and arterial blood oxygen levels, dramatically increase. We aim to understand how birth changes microvascular development in order to come up with ways to improve lifelong resilience to cardiac microvascular disease and cardiometabolic health.