The art of arteriogenesis.
The identification of collateral artery growth (arteriogenesis) as the only mechanism to compensate for the loss of an occluded artery forced us to define the mechanisms responsible for this type of vessel growth. To achieve this, a variety of coronary as well as peripheral models of arteriogenesis have been developed. Based on these studies it is obvious that arteriogenesis obeys different mechanisms than angiogenesis, the sprouting of capillaries. Upon occlusion of an artery, the blood flow is redirected into preexisting arteriolar anastomoses that experience increased mechanical forces such as shear stress and circumferential wall stress. The endothelium of the arteriolar connections is then activated, resulting in an increased release of monocyte-attracting proteins as well as an upregulation of adhesion molecules. Upon adherence and extravasation, monocytes promote arteriogenesis by supplying growth factors and cytokines that bind to receptors that are expressed on vascular cells within a limited time frame. Animal studies evidenced that factors, such as monocyte chemoattractant protein-1, granulocyte-monocyte colony-stimulating factor, or transforming growth factor-beta1, that either attract or prolong the lifetime of monocytes efficiently enhance collateral artery growth, an effect that was seen only to a minor degree after application of a single growth factor. Bone marrow-derived stems cells and endothelial progenitor cells do not incorporate in growing arteries but, rather, function as supporting cells. Complete elucidation of the mechanisms of arteriogenesis may lead to efficacious therapies counteracting the devastating consequences of vascular occlusive diseases.
Deindl
Elisabeth
E
Ludwig-Maximilians-University, Klinikum Grosshadern, Medical Clinic 1, Marchioninistr 15, D-81377 Munich, Germany. Elisabeth.Deindl@med.uni-muenchen.de
Schaper
Wolfgang
W
D000818:Animals; D001158:Arteries / Q000503:physiopathology*; D002199:Capillary Permeability; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D007511:Ischemia / Q000378:metabolism*; D040542:Mechanotransduction, Cellular; D009000:Monocytes / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D010958:Plasminogen / Q000378:metabolism; D014652:Vascular Diseases / Q000378:metabolism*
D005346:Fibroblast Growth Factors; D010958:Plasminogen