The evolution of the discipline of vascular biology: from systems physiology to molecular biology to molecular systems.

Abstract

The changes in vascular research over the past half century have been nothing short of extraordinary. From the evolution in technologies to the analytical process, advances that were not even imaginable 50 years ago have led to far-reaching insights into the biology of the blood vessel and the diseases that affect it. This period has also witnessed two major shifts in the general experimental paradigm of vascular biology. At mid-century, vascular biologists used physiological methods to attempt to understand phenotype. Their primary focus was on vascular tone and its neurohumoral determinants in health and disease. Limited by available methods, they were essentially unable to apply biochemical or molecular analysis to the characterization of vascular function. That situation, however, changed approximately 25 years later by which time modern techniques of cell culture were applied to vascular cells, and microanalytical methods, as well as novel reagents, became available for more precise molecular characterization of vascular phenotype. Of note, both of these historical phases of research in vascular biology used the conventional analytical regimen of reductionism: an investigator typically identified a vascular reflex or endothelial product of primary interest, asked a scientific question about the role of this reflex or molecule on vascular phenotype, designed experiments and controls that focused on that question, then drew inferences from the observed experimental result—without regard for other factors in the vessel that might influence the observed phenomenon. In the past decade, another major shift in the investigative paradigm has been developing as a result of access to large molecular data sets. The human genome project, together with expression array analysis, proteomics, and metabolomics, has begun to yield a rich treasure trove of data that offers the promise of great insight into understanding vascular biology and pathobiology. Yet, we are plagued by the limitations of conventional reductionist …