Unfortunately, clinical trials of two important blood-vessel growth factors - fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor (VEGF) - have not produced stellar results. Now researchers at Washington University School of Medicine in St. Louis have investigated a third signalling molecule - called Sonic hedgehog - that could overcome problems associated with FGF2 and VEGF therapy.
In a report, the team showed that activating hedgehog signals in adult mouse hearts led to an increase in the density of blood vessels in the heart. Their findings suggest that a drug treatment that turned on or increased hedgehog signals could provide substantial benefit to patients suffering from ischemic heart disease and myocardial infarctions and offer an alternative to invasive procedures like surgery or angioplasty.
"Research on development in embryonic mouse hearts has shown that the heart needs multiple factors expressed at the right time, in the right amounts and in the right pattern to grow blood vessels that function properly," says first author Kory Lavine, graduate student in molecular biology and pharmacology and student in the Medical Scientist Training Program. "The best way to achieve that is to use a factor that controls and coordinates the activity of multiple blood-vessel growth factors, and we've found that hedgehog has this ability."
The researchers showed that hedgehog controlled four growth factors: three VEGF proteins (termed VEGF A, B and C) and a protein called angiopoietin 2. They found that hedgehog is sufficient to stimulate normal development of blood vessels in embryonic mouse hearts - under hedgehog's control, the blood vessels spread out in an orderly fashion from the top of the ventricles of the growing heart to the bottom.
MEDICA.de; Source: Washington University School of Medicine