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Arteriosclerosis, Thrombosis, and Vascular Biology
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Published Online
on April 11, 2002

Arteriosclerosis, Thrombosis, and Vascular Biology. 2002
Published online before print April 11, 2002, doi: 10.1161/01.ATV.0000017728.55907.A9
A more recent version of this article appeared on June 1, 2002
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Submitted on January 7, 2002
Accepted on February 27, 2002

Regulation of Endothelial Cell Survival and Apoptosis During Angiogenesis

Emmanouil Chavakis and Stefanie Dimmeler *

From Molecular Cardiology, Department of Internal Medicine IV, University of Frankfurt, Frankfurt, Germany.

* To whom correspondence should be addressed. E-mail: Dimmeler{at}em.uni-frankfurt.de.

Abstract—The process of angiogenesis plays an important role in many physiological and pathological conditions. Inhibition of endothelial cell (EC) apoptosis providing EC survival is thought to be an essential mechanism during angiogenesis. Many of the angiogenic growth factors inhibit EC apoptosis. In addition, the adhesion of ECs to the extracellular matrix or intercellular adhesion promotes EC survival. In contrast, increasing evidence suggests that the induction of EC apoptosis may counteract angiogenesis. In this review, we focus on the regulation of EC survival and apoptosis during angiogenesis and especially on the effects and intracellular signaling promoted by angiogenic growth factors, endogenous angiogenic inhibitors (such as angiostatin, endostatin, and thrombospondin-1), and the adhesion to the extracellular matrix. Furthermore, we discuss the effects of cross talk between adhesion molecules and growth factors. Understanding the molecular mechanisms involved in the regulation of EC survival and apoptosis may provide new targets for the development of new therapies to enhance angiogenesis in the case of tissue-ischemia (eg, the neovascularization of myocardium) or to inhibit angiogenesis in the case of neovascularization-dependent disease (eg, tumor, diabetic retinopathy).


Key words: apoptosis • angiogenesis • growth factors • vascular endothelial growth factor • angiopoietin