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Circulation Research. 2004;95:449-458
doi: 10.1161/01.RES.0000141145.78900.44
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(Circulation Research. 2004;95:449.)
© 2004 American Heart Association, Inc.


Reviews

Influence of Mechanical, Cellular, and Molecular Factors on Collateral Artery Growth (Arteriogenesis)

Matthias Heil, Wolfgang Schaper

From the Max-Planck-Institute for Physiological and Clinical Research, Bad Nauheim, Germany.

Correspondence to Wolfgang Schaper, MD, PhD, Dsci, Max-Planck-Institute for Physiological and Clinical Research, Dept. of Experimental Cardiology, Benekestrasse 2, 61231 Bad Nauheim, Germany. E-mail w.schaper{at}kerckhoff.mpg.de

This Review is part of a thematic series on Angiogenesis, which includes the following articles:

Endothelial Progenitor Cells: Characterization and Role in Vascular Biology

Bone Marrow–Derived Cells for Enhancing Collateral Development: Mechanisms, Animal Data, and Initial Clinical Experiences

Influence of Mechanical, Cellular, and Molecular Factors on Collateral Artery Growth (Arteriogenesis)

Innate Immunity and Angiogenesis

Syndecans

Growth Factors and Blood Vessels: Differentiation and Maturation
Ralph Kelly Guest Editor

Growth of collateral blood vessels (arteriogenesis) is potentially able to preserve structure and function of limbs and organs after occlusion of a major artery. The success of the remodeling process depends on the following conditions: (1) existence of an arteriolar network that connects the preocclusive with the postocclusive microcirculation; (2) activation of the arteriolar endothelium by elevated fluid shear stress; (3) invasion (but not incorporation) of bone marrow–derived cells; and (4) proliferation of endothelial and smooth muscle cells. Most organs of most mammals including man can rely on the existence of interconnecting arterioles in most organs and tissues with heart being the exception in rodents and pigs. Arterial occlusion lowers the pressure in the distal vasculature thereby creating a pressure gradient favoring increased flow through preexisting collaterals. This increases fluid shear stress leading to endothelial activation with cellular edema, upregulation of adhesion molecules, mitogenic-, thrombogenic-, and fibrinolytic factors, leading to monocyte invasion with matrix digestion. Smooth muscle cells migrate and proliferate and the vessel enlarges under the influence of increasing circumferential wall stress. Growth factors involved belong to the FGF family and signaling proceeds via the Ras/Raf- and the Rho cascades. Increases in vascular radius and wall thickness restore fluid shear stress and circumferential wall stress to normal levels and growth stops. Although increases in collateral vessel size are very substantial their maximal conductance amounts to only 40% of normal. Forced increases in FSS can reach almost 100%.


Key Words: arteriogenesis • shear stress • monocytes • vascular remodeling • leukocytes




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