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

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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.