Introduction: Alterations of wall shear stress can predispose the endothelium to the development of atherosclerotic plaques. Ample evidence indicates that arginase expression and/or activity correlates with several risk factors for cardiovascular disease including atherosclerosis.

Methods: To evaluate the regulation of arginases by different shear stress patterns without neuroendocrine factors, we perfused carotid arterial segments to unidirectional high and low shear stress, and oscillatory shear stress. After 3 days of flow exposure, vascular function, arginase expression and localization were analyzed. We compared these well-controlled measurements to an in vivo model of shear stress-induced atherogenesis. In brief, the carotid artery of ApoE−/− mice, fed with high cholesterol diet, was exposed to similar hemodynamic conditions by the placement of a shear stress modifier for 9 weeks.

Results: Our results showed for the first time that exposure of carotid segments to high shear stress conditions (athero-protective) significantly decrease arginase II protein expression as compared to both low and oscillatory flow conditions. Immunohistochemisty analysis confirmed a pronounced expression of arginase II on SMCs and macrophages on in the atherosclerotic plaques formed by oscillatory and low shear stress in vivo.

Conclusions: The present study demonstrates that arginase expression is modulated by shear stress patterns in carotid arteries perfused ex vivo. Similar findings are also observed in a model of shear stress-induced atherogenesis in vivo. Histopathological analysis of carotid lesions in ApoE−/− mice exposed to shear stress and chronically treated with arginase inhibitors may further elucidate the role of arginases in modulating both plaque size and vulnerability.