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Journal Article

Arginase inhibition attenuates arteriogenesis and interferes with M2 macrophage accumulation

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Troidl,  Kerstin
Pharmacology, Max Planck Institute for Heart and Lung Research, Max Planck Society;

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Citation

Lasch, M., Caballero-Martinez, A., Troidl, K., Schloegl, I., Lautz, T., & Deindl, E. (2016). Arginase inhibition attenuates arteriogenesis and interferes with M2 macrophage accumulation. LABORATORY INVESTIGATION, 96(8), 830-838. doi:10.1038/labinvest.2016.62.


Cite as: http://hdl.handle.net/21.11116/0000-0001-BD28-E
Abstract
L-Arginine is the common substrate for nitric oxide synthases (NOS) and arginase. Whereas the contribution of NOS to collateral artery growth (arteriogenesis) has been demonstrated, the functional role of arginase remains to be elucidated and was topic of the present study. Arteriogenesis was induced in mice by ligation of the femoral artery. Laser Doppler perfusion measurements demonstrated a significant reduction in arteriogenesis in mice treated with the arginase inhibitor nor-NOHA (N-omega-hydroxy-nor-arginine). Accompanying in vitro results on murine primary arterial endothelial cells and smooth muscle cells revealed that nor-NOHA treatment interfered with cell proliferation and resulted in increased nitrate/nitrite levels, indicative for increased NO production. Immuno-histological analyses on tissue samples demonstrated that nor-NOHA administration caused a significant reduction in M2 macrophage accumulation around growing collateral arteries. Gene expression studies on isolated growing collaterals evidenced that nor-NOHA treatment abolished the differential expression of Icam1 (intercellular adhesion molecule 1). From our data we conclude that arginase activity is essential for arteriogenesis by promoting perivascular M2 macrophage accumulation as well as arterial cell proliferation.