Program Rationale

Recent progress in our ability to produce genetically altered animals that model human conditions has greatly contributed to developing a better understanding of the complex pathogenesis of human disease and the development of new therapies. Concepts concerning the presumed function of molecules, derived from studies at the cellular level, can now be tested at the whole organism level. Conversely, the culture of cells and intact vessels derived from genetically altered animals can supply reagents for furthering in vitro studies. Similarly, gene mutations and polymorphisms associated with disease in human patients can now be directly tested in mice for their causative relationship with the phenotype. To complement this, genes initially implicated in the pathogenesis of vascular diseases in mice can be studied in human populations to look for alleles that may account for susceptibility. Experiments to identify modifiers of disease likewise benefit greatly from being carried out in parallel in mice and humans.

The ability to go back and forth between cells and whole organisms and between humans and animal models is an integral part of state-of-the-art vascular biology. Knowledge of the genetic determinants of vascular diseases, aided by mouse studies, and of the molecular pathways, aided by in vitro studies, will allow us to identify disease prone persons and design specific preventative measures for many individuals, and treatments tailored for those for whom prevention is no longer an option.

Triangle

The pathogenesis of most vascular diseases is complex, polygenic and multifactorial. A problem in one cell type influences other cell types and affects their physiological processes; similarly a problem in one organ influences other organs. Furthermore, it has become clear that there are strong interactions between vascular diseases and other diseases. Multiple organ systems, cell types, disease conditions and disciplines constitute any currently relevant study of vascular biology. Clearly, it is increasingly difficult for an individual investigator to make substantial contributions to the scientific advancement of the field without collaborating with scientists in multiple fields. Thus there is an acute need to integrate the knowledge in all areas of vascular biology, and to train the next generation of scientists so that they have a broad understanding of cross-disciplinary research.