In mammals, there are two isoforms of arginase, namely, arginase Ⅰ and arginase Ⅱ. Arginase Ⅰ is strongly expressed in liver cytosol and arginase Ⅱ highly expressed in kidney mitochondria
[17-18]. Arginase Ⅰ is responsible for the hydrolysis of L-arginine into urea and ornithine, competes directly with endothelial nitricoxide synthase (eNOS) for their shared substrate, L-arginine and providing ornithine for the synthesis of polyamines and proline. Polyamines are involved in cell growth and differentiation, whereas proline is a key component of collagen
[19-21]. Hence, increases in arginase activity can decrease tissue and cellular arginine levels and reduce eNOS bioavailability. This may lead to decrease NO production. Enhanced arginase activity has been implicated in a number of conditions characterized by vascular dysfunction
[22-23]. The pathological process is characterized by impaired vascular endothelial cell production of the vasodilator and antiplatelet adhesion factor NO and/or decreased NO bioavailability
[24]. NO production by eNOS in endothelial cells is critically involved in maintaining the integrity and stability of the vascular endothelium, preventing platelet adhesion and aggregation and monocyte adhesion and maintaining blood ?ow. Impaired production or biological activity of NO released from vascular endothelium is a central mechanism of endothelial dysfunction in numerous vascular disceases
[25-26]. According to above mentioned pathological process, plenty of studies have suggested that arginase Ⅰ overexpression may be deleterious by contributing to the endothelial dysfunction observed in vascular disorders including pulmonary hypertension, atherosclerosis, aging-associated endothelial dysfunction, ischemia/reperfusion injury
[20-21, 27].
In our real-time PCR experiment for comparing expression level of arginase Ⅰ showed that, the expression of arginase Ⅰ in the peak thrombosis group was higher than that of the control, initial thrombosis, and non-thrombosis group. Our study provides the first evidence that arginase Ⅰ may be one of the most important factor influence the process of DVT formation and may be a leading factor in venous diseases that arginase competes with NOS for the catabolism of L-arginine and that the inhibition of arginase allows increased production of NO. This experiment revealed that arginase Ⅰ may activated during the course of thrombosis, then inhibit eNOS expression, lead to the reduction of NO, anticoagulation may followed by thrombolus formation. But the relationship between arginase Ⅰ and platelet aggregation, eNOS and endothelial dysfunction remain incompletely understood and its mechanism would be further investigated[28-31]. We anticipate that a better understanding of the vascular arginase/NOS signaling pathway, as well as reaction kinetics of each enzyme in the intact/dysfunctional vascular tissue, can yield important information for understand and explore the complex mechanism of DVT.
