Arginase Promotes Neointima Formation in Rat Injured Carotid Arteries
Peyton, Kelly J.; Ensenat, Diana; Azam, Mohammed A.; Keswani, Amit N.; Kannan, Sankaranarayanan; Liu, Xiao-ming; Wang, Hong; Tulis, David A.; Durante, William
Objective—Arginase stimulates the proliferation of cultured vascular smooth muscle cells (VSMCs); however, the influence of arginase on VSMC growth in vivo is not known. This study investigated the impact of arginase on cell cycle progression and neointima formation following experimental arterial injury. Methods and Results—Balloon injury of rat carotid arteries resulted in a sustained increase in arginase activity in the vessel wall and the induction of arginase I protein in both the media and neointima of injured vessels. Furthermore, local perivascular application of the potent and selective arginase inhibitors S-(2-boronoethyl)-L-cysteine (BEC) or NG-hydroxy-nor-L-arginine (L-OHNA) immediately after injury markedly attenuated medial and neointimal DNA synthesis and neointima formation. Substantial arginase I protein and arginase activity was also detected in rat cultured aortic VSMCs. Moreover, treatment of VSMCs with BEC or L-OHNA, or knockdown of arginase I protein, arrested cells in the G0/G1 phase of the cell cycle and induced the expression of the cyclin-dependent protein kinase inhibitor, p21. Conclusion—This study demonstrates that arginase is essential for VSMCs to enter the cell cycle and that arginase I contributes to the remodeling response following arterial injury. Arginase I represents a potentially new therapeutic target for the treatment of vasculoproliferative disorders.Originally published Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 29, No. 4, Apr 2009
Peyton, Kelly J., & Ensenat, Diana, & Azam, Mohammed A., & Keswani, Amit N., & Kannan, Sankaranarayanan, & Liu, Xiao-ming, & Wang, Hong, & Tulis, David A., & Durante, William. (April 2009). Arginase Promotes Neointima Formation in Rat Injured Carotid Arteries. Arteriosclerosis, Thrombosis, and Vascular Biology, 29(4), 488- 494. Retrieved from http://hdl.handle.net/10342/3371
Peyton, Kelly J., and Ensenat, Diana, and Azam, Mohammed A., and Keswani, Amit N., and Kannan, Sankaranarayanan, and Liu, Xiao-ming, and Wang, Hong, and Tulis, David A., and Durante, William. "Arginase Promotes Neointima Formation in Rat Injured Carotid Arteries". Arteriosclerosis, Thrombosis, and Vascular Biology. 29:4. (488-494), April 2009. December 17, 2018. http://hdl.handle.net/10342/3371.
Peyton, Kelly J. and Ensenat, Diana and Azam, Mohammed A. and Keswani, Amit N. and Kannan, Sankaranarayanan and Liu, Xiao-ming and Wang, Hong and Tulis, David A. and Durante, William, "Arginase Promotes Neointima Formation in Rat Injured Carotid Arteries," Arteriosclerosis, Thrombosis, and Vascular Biology 29, no. 4 (April 2009), http://hdl.handle.net/10342/3371 (accessed December 17, 2018).
Peyton, Kelly J., Ensenat, Diana, Azam, Mohammed A., Keswani, Amit N., Kannan, Sankaranarayanan, Liu, Xiao-ming, Wang, Hong, Tulis, David A., Durante, William. Arginase Promotes Neointima Formation in Rat Injured Carotid Arteries. Arteriosclerosis, Thrombosis, and Vascular Biology. April 2009; 29(4): 488-494. http://hdl.handle.net/10342/3371. Accessed December 17, 2018.
East Carolina University