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Critical limb threatening ischemia (CLTI) is a significant unresolved health issue for a growing percent of the population. In this disease, arterial blockage reduces blood flow to the muscles of the lower leg, which is referred to as ischemia. Individuals with CLTI suffer a range of negative outcomes, including limb amputation and death. Clinical treatments to restore blood flow to the limb can delay the need for limb amputation but have had limited success in improving patient health. Particularly, the ischemic muscle remains damaged, which results not just in limited mobility but also lowers overall health. We will examine a specific type of cell within blood vessels, called a pericyte, and whether it contributes to the problems seen in the ischemic muscle. We will conduct analyses of patient sample and use a combination of animal models and cultured cell experiments. By tracking the transition in what happens to these pericytes during ischemia, and through examining what triggers them to behave in deleterious ways, we will identify potential new ways to improve the health of CLI patients.