Effects of aging, hypertension and diabetes on the mouse brain and heart vasculomes

Abstract The emerging concept of the vasculome suggests that microvessels contribute to function and dysfunction in every organ. In the brain, aging and comorbidities such as hypertension and diabetes significantly influence a wide variety of neurodegenerative and cerebrovascular disorders, but the underlying mechanisms are complex and remain to be fully elucidated. Here, we hypothesize that aging, hypertension and diabetes perturb gene networks in the vasculome. Microvascular endothelial cells were isolated from mouse brain and heart, and their transcriptomes were profiled with microarrays. For aging, we compared 5 mo vs 15 mo old C57BL6 male mice. For hypertension, we compared 4 mo old normotensive BPN vs hypertensive BPH male mice. For diabetes, we compared 3 mo old diabetic db/db mice with their matching C57BLKS controls. Four overall patterns arose from these comparative analyses. First, organ differences between brain and heart were larger than effects of age and co-morbidities per se. Second, across all conditions, more genes were altered in the brain vasculome compared with the heart. Third, age, hypertension and diabetes perturbed the brain and heart vasculomes in mostly distinct ways, with little overlap. Fourth, nevertheless, a few common pathways were detected in the brain, expressed mostly as a suppression of immune response. These initial drafts of the brain and heart vasculomes in the context of aging and vascular comorbidities should provide a framework for designing future investigations into potential targets and mechanisms in CNS disease.