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，当它们的毛细血管没有足够的血液注入时，它们会遇到类似的问题，包括收缩功能差、对胰岛素的抵抗和萎缩。在发育过程中，心脏和骨骼肌的小血管或微血管的生长方式已被证明会影响终生的恢复能力或这些问题的风险。出生代表了影响微血管生长和发育的已知因素的重大变化，包括心脏和骨骼肌负荷的变化，以及随着肺部取代胎盘，动脉血的氧合急剧增加。众所周知，出生后微血管会发生发育变化，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，我们将使用大型动物模型（羊）来研究出生前后心脏微血管和骨骼肌的功能变化，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。意义：微血管生长对宫内条件有反应，已知发育条件会影响终生的恢复能力和心脏和心脏代谢疾病的风险。出生是发育的一个重要过渡点，已知影响微血管生长的因素，包括肌肉负荷和动脉血氧水平，急剧增加。我们的目标是了解出生是如何改变微血管发育的，以便找到改善心脏微血管疾病和心脏代谢健康的终身恢复能力的方法。

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.