Editing Angiogenesis (section)

===Angiogenesis as a therapeutic target===
Angiogenesis may be a target for combating diseases such as [[heart disease]] characterized by either poor vascularisation or abnormal vasculature.<ref>{{cite journal | vauthors = Ferrara N, Kerbel RS | title = Angiogenesis as a therapeutic target | journal = Nature | volume = 438 | issue = 7070 | pages = 967–974 | date = December 2005 | pmid = 16355214 | doi = 10.1038/nature04483 | s2cid = 1183610 | bibcode = 2005Natur.438..967F }}</ref> Application of specific compounds that may inhibit or induce the creation of new [[blood vessels]] in the body may help combat such diseases. The presence of blood vessels where there should be none may affect the mechanical properties of a tissue, increasing the likelihood of failure. The absence of blood vessels in a repairing or otherwise metabolically active tissue may inhibit repair or other essential functions. Several diseases, such as [[ischemia|ischemic chronic wounds]], are the result of failure or insufficient blood vessel formation and may be treated by a local expansion of blood vessels, thus bringing new nutrients to the site, facilitating repair. Other diseases, such as age-related [[macular degeneration]], may be created by a local expansion of blood vessels, interfering with normal physiological processes.

The modern clinical application of the principle of angiogenesis can be divided into two main areas: anti-angiogenic therapies, which angiogenic research began with, and pro-angiogenic therapies. Whereas anti-angiogenic therapies are being employed to fight cancer and malignancies,<ref>{{cite journal | vauthors = Folkman J, Klagsbrun M | title = Angiogenic factors | journal = Science | volume = 235 | issue = 4787 | pages = 442–447 | date = January 1987 | pmid = 2432664 | doi = 10.1126/science.2432664 | bibcode = 1987Sci...235..442F }}</ref><ref>{{cite journal | vauthors = Folkman J | title = Fighting cancer by attacking its blood supply | journal = Scientific American | volume = 275 | issue = 3 | pages = 150–154 | date = September 1996 | pmid = 8701285 | doi = 10.1038/scientificamerican0996-150 | bibcode = 1996SciAm.275c.150F }}</ref> which require an abundance of [[oxygen]] and nutrients to proliferate, pro-angiogenic therapies are being explored as options to treat [[cardiovascular diseases]], the number one cause of death in the [[Western world]]. One of the first applications of pro-angiogenic methods in humans was a German trial using fibroblast growth factor 1 (FGF-1) for the treatment of coronary artery disease.<ref name="Stegmann">{{cite journal | vauthors = Stegmann TJ | title = FGF-1: a human growth factor in the induction of neoangiogenesis | journal = Expert Opinion on Investigational Drugs | volume = 7 | issue = 12 | pages = 2011–2015 | date = December 1998 | pmid = 15991943 | doi = 10.1517/13543784.7.12.2011 }}</ref><ref name="Schumacher">{{cite journal | vauthors = Stegmann TJ, Hoppert T, Schneider A, Gemeinhardt S, Köcher M, Ibing R, Strupp G | title = [Induction of myocardial neoangiogenesis by human growth factors. A new therapeutic approach in coronary heart disease] | language = de | journal = Herz | volume = 25 | issue = 6 | pages = 589–599 | date = September 2000 | pmid = 11076317 | doi = 10.1007/PL00001972 | s2cid = 21240045 }}</ref><ref>{{cite journal | vauthors = Folkman J | title = Angiogenic therapy of the human heart | journal = Circulation | volume = 97 | issue = 7 | pages = 628–629 | date = February 1998 | pmid = 9495294 | doi = 10.1161/01.CIR.97.7.628 | doi-access = free }}</ref><ref>{{cite journal |last1=Zarei |first1=Parvin  |last2=Ghasemi |first2=Fahimeh |title=The Application of Artificial Intelligence and Drug Repositioning for the Identification of Fibroblast Growth Factor Receptor Inhibitors: A Review |journal=Advanced Biomedical Research|date=2024 |language=en |volume=13 |issue=15 |pages=9759–9815 |doi= 10.4103/abr.abr_170_23 |doi-access=free |pmid=38525398 |pmc=10958741 }}</ref>

Regarding the [[mechanism of action]], pro-angiogenic methods can be differentiated into three main categories: [[gene therapy]], targeting genes of interest for amplification or inhibition; [[protein replacement therapy]], which primarily manipulates angiogenic growth factors like [[FGF-1]] or [[vascular endothelial growth factor]], VEGF; and cell-based therapies, which involve the implantation of specific cell types.

There are still serious, unsolved problems related to gene therapy. Difficulties include effective integration of the therapeutic genes into the genome of target cells, reducing the risk of an undesired immune response, potential toxicity, [[immunogenicity]], inflammatory responses, and [[oncogenesis]] related to the viral vectors used in implanting genes and the sheer complexity of the genetic basis of angiogenesis. The most commonly occurring disorders in humans, such as heart disease, high blood pressure, diabetes and [[Alzheimer's disease]], are most likely caused by the combined effects of variations in many genes, and, thus, injecting a single gene may not be significantly beneficial in such diseases.{{citation needed|date=August 2018}}

By contrast, pro-angiogenic protein therapy uses well-defined, precisely structured proteins, with previously defined optimal doses of the individual protein for disease states, and with well-known biological effects.<ref name="Santulli_2013"/> On the other hand, an obstacle of protein therapy is the mode of delivery. Oral, intravenous, intra-arterial, or intramuscular routes of protein administration are not always as effective, as the therapeutic protein may be metabolized or cleared before it can enter the target tissue. Cell-based pro-angiogenic therapies are still early stages of research, with many open questions regarding best cell types and dosages to use.