Introduction: Aterations of wall shear stress can predispose the endothelium to the development of atherosclerotic plaques. Ample evidence indicates that arginase expression/activity correlates with several risk factors for cardiovascular disease including atherosclerosis. However, the role of arginase pathway in response to shear stress has never been investigated.

Methods: To evaluate the regulation of arginases by different shear stress patterns without neuroendocrine factors, we perfused carotid arterial segments for 3 days to unidirectional high and to low oscillatory shear stress hemodynamic conditions. We compared these well-controlled measurements to an in vivo model of shear stress-induced atherogenesis. Vasoreactivity, immunohistochemistry and Western blot were used to characterize the role of arginase pathway.

Results: Our results from ex vivo perfusion arteries showed for the first time that exposure of carotid to oscillatory flow significantly increase arginase II protein expression and activity as compared to high shear stress flow condition (athero-protective). Our data suggested that arginase I and II are also regulated by shear stress in vivo. Arginases were up-regulated on EC, SMC and macrophages of carotid segments exposed either to low stress or to oscillatory shear stress conditions. Both plaque size and composition were differentially modulated in mice chronically treated with arginase inhibitor, nor-ω- hydroxy-nor-L-arginine for 9 weeks (10mg/kg/day, i.p)

Conclusions: The present study demonstrates that arginase expression is already modulated by 3 days exposure to different shear stress patterns in carotid arteries perfused ex vivo. Similar findings are also observed in a model of shear stress-induced atherogenesis in vivo.