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(Circulation Research. 2007;101:536.)
© 2007 American Heart Association, Inc.

Editorials

Substrate Matters

Reciprocally Stimulatory Integrin and VEGF Signaling in Endothelial Cells

Ebba Brakenhielm

From Inserm U644, Institute for Biomedical Research, Rouen University Medical School, Rouen, France.

Correspondence to Dr Ebba Brakenhielm, Inserm U644, UFR de Médicine-Pharmacie, 22 Boulevard Gambetta, 76 183 Rouen, France. E-mail Ebba.Brakenhielm@univ-rouen.fr

See related article, pages 570–580

Key Words: angiogenesis • extracellular matrix • signaling pathways • src kinase • VEGF receptor

An extract of the first 250 words of the full text is provided, because this article has no abstract.

	Introduction

 
The integrin family of transmembrane receptors is composed of heterodimers of different and ß subunits that direct cellular adhesion to extracellular matrix (ECM) components such as collagens, laminins, fibronectin, and vitronectin. Certain members of the integrin family, such as ₂ß₁, ₅ß₁, _vß₃, and _vß₅ integrins, are specifically upregulated in endothelial cells during angiogenesis, eg, during vascular remodeling and growth associated with inflammation, wound healing, ischemic injury, or tumor growth.¹ Functional inhibition of these integrins, via blocking antibodies or cyclic peptide antagonists, has been found to reduce angiogenic responses to growth factors, ischemia, and tumors.² Thus, in addition to their involvement in steady-state maintenance of blood vessel integrity, integrins seem to play an essential role in the carry-out of angiogenic programs in activated endothelial cells.

The integrin signaling is bidirectional and encompasses both outside-in signals, eg, activation of second messenger pathways in response to changes in ECM composition, and inside-out signals, eg, changes in cellular adhesion and motility in response to growth factor stimulation.³ In addition, there is a degree of interdependence between the cellular circuits processing ECM-derived signals and soluble growth factor–derived signals. For instance, growth factor–induced responses are modulated by cellular adhesion, and integrin-mediated outside-in signals, dependent on the specific type of integrin molecule(s) engaged by the ECM, seem to directly influence growth factor receptor signaling pathways.^4,5

The reciprocal communication between integrins and growth factor receptors most likely acts to integrate and coordinate cellular activity in response to different types of stimuli. However, the molecular mechanisms . . . [Full Text of this Article]

Related Article:

Mechanisms of Integrin–Vascular Endothelial Growth Factor Receptor Cross-Activation in Angiogenesis

Ganapati H. Mahabeleshwar, Weiyi Feng, Kumar Reddy, Edward F. Plow, and Tatiana V. Byzova
Circ. Res. 2007 101: 570-580. [Abstract] [Full Text] [PDF]