Our findings in mice of an important role for BACE1 and Aβ42 in vascular dysfunction can be translated to humans, where we show localization of BACE1 protein in endothelial cells and VSMCs in human temporal artery, with increased BACE1 transcript levels in internal mammary arteries associated with obesity, but not diabetes. The gene discussed is BACE1; the disease is obesity due to melanocortin 4 receptor deficiency.