Cardiovascular Research Advance Access originally published online on March 3, 2008
Cardiovascular Research 2008 78(2):232-241; doi:10.1093/cvr/cvn058
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Neural guidance molecules, tip cells, and mechanical factors in vascular development
1 Department of Angiogenesis and Cardiovascular Pathology, Max Delbrueck Center for Molecular Medicine (MDC), Robert Roessle Strasse 10, 13125 Berlin, Germany
2 Department of Physiology, Charité Berlin, Arnimallee 22, 14195 Berlin, Germany
3 Department for Cardiology, Research Group for Experimental and Clinical Arteriogenesis, Campus Virchow and Campus Mitte, Center for Cardiovascular Research (CCR), Charité Berlin, Hessische Strasse 3-4, 10115 Berlin, Germany
* Corresponding author. Tel: +49 30 9406 3892/3894; fax: +49 9406 3850. E-mail address: lenoble{at}mdc-berlin.de
The vascular system is generated and maintained by reactions of blood vessels to stimuli of several types. The basic outline of the vascular system is determined during development by genetic programming, guided by the unique temporal and spatial patterns of structural and molecular features available in the embryo. With establishment of blood flow, control of vascular development is increasingly taken over by feedback signals derived from vascular function, including blood flow and pressure, in addition to those derived from the metabolic state of the tissue. Mechanical and molecular signals also govern the post-natal structural adaptation of vascular beds in response to functional requirements, both during normal, physiological conditions (growth, exercise) and during pathophysiological conditions including ischaemic diseases and tumour growth. The orderly structure of vascular beds emerges as each vessel segment reacts to the local conditions and stimuli that it experiences, according to a common set of genetically determined responses. In this process of angioadaptation, the properties and architecture of vascular beds are determined by the continuous interplay between vascular and cellular reactions to haemodynamic and molecular signals and the functional implications of these reactions, constituting a complex feedback system. Here, studies on vascular development and adaptation in response to haemodynamic and molecular factors are integrated, with emphasis on arterial-venous network development and structural adaptation of vessels.
KEYWORDS Angiogenesis; Arteriogenesis; Haemodynamics; Shear stress; Wall stress; Tip cells; neural guidance molecules; Mechanosensing; Vascular development; Embryo
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