Inhibition of angiogenesis

Angiogenesis -- the growth of blood capillaries -- is critical for normal development, and leads to many diseases, including blindness, when it becomes deregulated. Although much is known about soluble angiogenic factors, such as VEGF, that stimulate capillary formation, little is known about how mechanical forces influence this process of cellular self assembly. The Ingber team recently described a new mechanosensitive transcriptional control mechanism that governs angiogenesis in vitro and in vivo (Mammoto et al. Nature 2009), in which the compliance (stiffness) of the extracellular matrix influences expression of the VEGFR2 receptor by altering the balance between two mutually antagonistic transcription factors  -- TFII-I and GATA2 -- controls VEGFR2 expression. This same pathway is sensitive to soluble VEGF. Thus, this is the first known functional cross-antagonism between transcription factors that controls tissue morphogenesis, and that responds to both mechanical and chemical cues.  This fluorescence microscopic image shows the forming retinal vascular network of the newborn mouse, which has been slowed in its development by genetically manipulating this mechanosensitive transcriptional control system. [Image by Akiko Mammot, the Ingber Lab.]

A mechanosensitive transcriptional mechanism that controls angiogenesis. Mammoto A, Connor KM, Mammoto T, Yung CW, Huh D, Aderman CM, Mostoslavsky G, Smith LE, Ingber DE. Nature. 2009 Feb 26;457(7233):1103-8.