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Background Perturbations in vascular health can have widespread and long-term consequences in the cardiovascular system increasing the risk of developing atherosclerosis, hypertension, stroke, and heart attack. Perivascular adipose tissue (PVAT) surrounds blood vessels and in health; exerts anticontractile properties on the vasculature. In cardiovascular disease, these properties are perturbed, exacerbating vascular dysfunction.The protease β-site APP-cleaving enzyme 1 (BACE1) originally was an enzyme of interest in Alzheimer’s disease research as BACE1 was found to be involved in producing β-amyloid plaques. However, research has shown that BACE1 plays a role in obesity and cardiovascular disease. This study aims to determine if inhibition of BACE1 can have advantageous effects in blood vessel function via modulation of PVAT functions.Methods Murine mesenteric blood vessels between second and third order vessels were dissected out and isolated for wire myography. Contractility studies were performed on transgenic mice lacking BACE1 in adipocytes or on tissues incubated with a BACE1 inhibitor. Studies were performed in the presence and absence of PVAT.Results Our results show that PVAT incubated with a BACE1 inhibitor (Merck-3,1uM for 1 hour) had a significantly enhanced anticontractile effect compared to vessels without BACE1 inhibitor (P<0.05). There was also a significant difference in vessel anti-contractility with PVAT from transgenic mice lacking BACE1 in the adipocytes (P<0.01).Conclusion Overall, our data demonstrates that BACE1 regulates PVAT function and has a role in vessel contractility. Taken together with the literature, BACE1 activity drives adipose tissue dysfunction and exacerbates vascular dysfunction. This indicates that targeting BACE1 with inhibitors, several of which have been shown to be safe in clinical trials, may be a novel therapeutic for treating vascular disease.