NOTCH Signaling Networks in Perivascular Adipose Tissue

Over a hundred years ago, mutants were detected in Drosophila melanogaster that led to a NOTCH in the wing tip. This original phenotype was reflected in the nomenclature of the gene family that was later cloned and characterized in the 1980s and found to be conserved across metazoans. NOTCH signaling relies on transmembrane ligands and receptors that require cellular contact for receptor activation, reflecting its role in multicellular organisms as an intercellular signaling strategy. In humans, mutations in genes encoding NOTCH and their ligands have been shown to promote human disease; these aspects have been extensively reviewed. Notch signaling plays important roles in vascular development (vasculogenesis and angiogenesis) and homeostasis. NOTCH signaling is also active in adipose tissue and contributes to adipocyte differentiation. In addition, NOTCH activity regulates functions of other metabolic organs. This review focuses on NOTCH activity in perivascular adipose tissue within the vascular microenvironment as defined by mouse studies and summarizes expression and potential signaling of the NOTCH signaling network in human perivascular adipose tissue. Due to the strong activity of NOTCH in regulation of metabolic function, activation of the NOTCH network in specific cell types in perivascular adipose tissue has implications for signaling to the underlying blood vessel and control of vascular health and disease.