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We use high resolution bioluminescence metabolic imaging to study energy metabolism in two mechanistically different vascular pathologies: patent ductus arteriosus and atherosclerosis. Physiological energy depletion in postnatally constricting ductus arteriosus promotes permanent closure. Insufficient ductus energy depletion, common in preterm infants, is associated with persistent patent ductus arteriosus, a condition with significantly increased morbidity and mortality. In contrast, in atherosclerosis, energy depletion in the macrophage\u2010rich lesion core promotes cell death contributing to lesion instability and disease progression. (\u00a9 2012 WILEY\u2010VCH Verlag GmbH &amp; Co. 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