Editing Angiogenesis (section)

===Angiogenesis for cardiovascular disease===
Angiogenesis represents an excellent therapeutic target for the treatment of cardiovascular disease. It is a potent, physiological process that underlies the natural manner in which our bodies respond to a diminution of blood supply to vital organs, namely ''neoangiogenesis'': the production of new collateral vessels to overcome the ischemic insult.<ref name="Stegmann"/> A large number of preclinical studies have been performed with protein-, gene- and cell-based therapies in animal models of cardiac ischemia, as well as models of peripheral artery disease. Reproducible and credible successes in these early animal studies led to high enthusiasm that this new therapeutic approach could be rapidly translated to a clinical benefit for millions of patients in the Western world with these disorders. A decade of clinical testing both gene- and protein-based therapies designed to stimulate angiogenesis in underperfused tissues and organs, however, has led from one disappointment to another. Although all of these preclinical readouts, which offered great promise for the transition of angiogenesis therapy from animals to humans, were in one fashion or another, incorporated into early stage clinical trials, the FDA has, to date (2007), insisted that the primary endpoint for approval of an angiogenic agent must be an improvement in exercise performance of treated patients.<ref>{{cite journal | vauthors = Hariawala MD, Sellke FW | title = Angiogenesis and the heart: therapeutic implications | journal = Journal of the Royal Society of Medicine | volume = 90 | issue = 6 | pages = 307–311 | date = June 1997 | pmid = 9227376 | pmc = 1296305 | doi = 10.1177/014107689709000604 }}</ref>

These failures suggested that either these are the wrong molecular targets to induce neovascularization, that they can only be effectively used if formulated and administered correctly, or that their [[presentation (medical)|presentation]] in the context of the overall cellular microenvironment may play a vital role in their utility. It may be necessary to present these proteins in a way that mimics natural signaling events, including the [[concentration]], [[space|spatial]] and [[Time|temporal]] profiles, and their simultaneous or sequential presentation with other appropriate factors.<ref>{{cite journal | vauthors = Cao L, Mooney DJ | title = Spatiotemporal control over growth factor signaling for therapeutic neovascularization | journal = Advanced Drug Delivery Reviews | volume = 59 | issue = 13 | pages = 1340–1350 | date = November 2007 | pmid = 17868951 | pmc = 2581871 | doi = 10.1016/j.addr.2007.08.012 }}</ref>