Angiogenesis and microvascular remodeling: a brief history and future roadmap.

Angiogenesis and vessel remodeling determine the integrative control of the architectural structure and functional behaviors of the microcirculation over the lifetime of an organism. Vascular remodeling is the basis of promising therapeutic strategies, including vascularization of ischemic organs. The history of angiogenesis research is long-more than 250 years-and the Microcirculatory Society has been the birthplace of numerous techniques, assays, and scientific concepts that have stimulated massive research endeavors in the pharmaceutical and medical arena. At present, angiogenesis isa dynamic field in which the molecular genetic and proteomic components of the process are still being identified, while integrative systems approaches are once again being recognized as essential to understand microvascular assembly in vivo across multiple scales from cells to whole vessel networks. A short history of people and ideas in this field is presented, followed by discussion of emerging directions receiving intense attention today and major questions that remain unanswered. The primary conclusion is that the need for scientists trained in the integrative approaches nurtured by the Microcirculatory Society over the past 50 years has never been greater, as it is clear that a complete mechanistic understanding of vessel adaptation (based on genomic and proteomic supporting casts) will now require deeper studies of angiogenesis and microvascular remodeling in the exquisite complexity of the native microenvironment-the microcirculation.