Patient-specific modeling of hypoxic response and microvasculature dynamics

Abstract

Human life evolved in the presence of oxygen, and even small alterations to this essential element can trigger a cascade of biological events. Conditions affecting how we metabolize oxygen and respond to hypoxia determine whether we thrive or succumb to disease. Physiological processes such as exercise, aging, hormonal cycle, and wound healing depend on genetic, epigenetic, and protein level changes in hypoxic response. Furthermore, all leading causes of death in the USA involve hypoxia and alter the microvasculature, through increases or decreases in the degree of angiogenesis (i.e., the growth capillaries from preexisting blood vessels). Patient variability - both in physiological and pathological conditions - determines how a given individual will respond to hypoxic exposure, and therapies targeting hypoxic pathways. The degree and breadth of patient variability is so wide regarding oxygen sensing and response, that computational modeling has become necessary to capture its complexity.