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Arteriogenesis, a new concept of vascular adaptation in occlusive disease

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Abstract

The formation of collateral arteries as a process adaptive to arterial occlusion is now called ‘arteriogenesis’ to emphasize the difference to angiogenesis, the formation of capillaries by sprouting from pre-existent ones (W. Schaper, I. Buschmann. Cardiovasc Res 1999; 43: 835–7; I. Buschmann, W. Schaper. J Pathol 2000; 190: 338–42; D. Scholz et al. Virchows Arch 2000; 436: 257–70). The differences are that collaterals develop from pre-existing arterioles and that circulating monocytes adhere to endothelium that had been activated by the high shear stress generated by the large pressure differences between perfusion territories. Monocytes are the major producers of growth factors and of proteolytic enzymes that enable smooth muscle cells to migrate and divide. The nature of the growth factors remains uncertain. Neither FGF-1/2 nor VEGF is expressed on the transcriptional or translational level in collaterals proper and in the tissue surrounding them. Only FGF receptor 1 has a brief window of upregulation shortly after arterial occlusion. While transgenic overexpression of FGF-1 increases number and branching of arterioles, targeted disruption of FGF-1/2 does not negatively influence arteriogenesis. Cytokines that attract monocytes or prolong the life span of monocytes (MCP-1, GM CSF) are strong arteriogenic factors. Collateral vessels exhibit the same morphology whether they had formed in the heart, limbs or brain or in dogs, rabbits or mouse. They are tortuous because they also increase lengthwise in a restricted space. In animals larger than the mouse, they develop an intima, and initially, many arterioles participate in arteriogenesis, but only a few mature into large arterial channels which, when arterial occlusion had proceeded slowly enough, can replace the occluded artery to a significant proportion. Therapy with a single growth factor in animals with occluded femoral arteries significantly increases the speed of arteriogenesis but does not significantly increase the level of adaptation. It appears that the mastergene for arteriogenesis still awaits discovery.

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Authors and Affiliations

  1. Department of Cardiac Surgery, Kerckhoff-Clinic, Bad Nauheim, Germany

    Dimitri Scholz

  2. Department of Anatomy, Hunan Medical University, Changsha, Hunan, P.R. China

    Wei-jun Cai

  3. Department of Experimental Cardiology, Max Planck Institute, Benekestrasse 2, 61231, Bad Nauheim, Germany. Tel:

    Wolfgang Schaper

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  1. Dimitri Scholz
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  2. Wei-jun Cai
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  3. Wolfgang Schaper
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Scholz, D., Cai, Wj. & Schaper, W. Arteriogenesis, a new concept of vascular adaptation in occlusive disease. Angiogenesis 4, 247–257 (2001). https://doi.org/10.1023/A:1016094004084

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