During the past several decades, landmark discoveries in the field of vascular biology have evolved our understanding of the biology of blood vessels and the pathobiology of local and systemic vascular disease states and have led to novel disease-modifying therapies for patients. In 1980, Furchgott and Zawadzki1 radically changed our focus in blood vessel research with the discovery of endothelium-derived nitric oxide and its effects on vascular tone. This seminal discovery redefined blood vessels as dynamic organs with autocrine, paracrine, and endocrine functions that are capable of regulating their own environment. The later recognition that many risk factors associated with vascular disease perturb nitric oxide-mediated homeostatic mechanisms lent further credence to the concept of blood vessels as complex organs rather than inert tubes. In the decades to follow, research in vascular biology predominantly targeted 3 facets of vascular function: vasomotor tone, inflammation, and the balance between thrombosis and thrombolysis. This occurred because atherosclerotic cardiovascular disease reached epidemic levels and atherothrombosis was found to feature disturbances in these functions that preceded visible pathology and clinical manifestations of the disease. Furthermore, modification of responsible causal factors reversed impaired vascular function (eg, lowering levels of low-density lipoproteins in atherosclerosis), and clinical studies began to validate the importance of preclinical vascular biology research in the treatment of hypertension, atherosclerosis, pulmonary vascular disease, erectile dysfunction, Raynaud phenomenon, and neointimal proliferation after mechanical vascular intervention. More recently, advances in molecular biology and –omics technologies have facilitated in vitro and in vivo studies that revealed that blood vessels regulate their own redox milieu, metabolism, mechanical environment, and phenotype, in part, through complex interactions between cellular components of the blood vessel wall and circulating factors. These interactors include stem, progenitor, and differentiated cells; microRNAs, long noncoding RNAs, and DNA; and, hormones, proteins, and lipids. Dysregulation of these …