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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:47.)
© 2008 American Heart Association, Inc.

Integrative Physiology/Experimental Medicine

Increased Smooth Muscle Cell Activation and Neointima Formation in Response to Injury in AIF-1 Transgenic Mice

Laura J. Sommerville; Sheri E. Kelemen; Michael V. Autieri

From the Department of Physiology, Independence Blue Cross Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, Pa.

Correspondence to Michael Autieri, PhD, Temple University School of Medicine, 810, MRB, 3420 North Broad Street, Philadelphia, PA 19140. E-mail mautieri{at}temple.edu

Abstract

Objective— Allograft Inflammatory Factor-1 (AIF-1) is a calcium binding scaffold protein which is rapidly induced in vascular smooth muscle cells (VSMCs) in response to injury and inflammation. A transgenic mouse in which AIF-1 expression was driven by a VSMC-specific SM22 promoter was generated to establish a direct relationship between AIF-1 expression and intimal hyperplasia.

Methods and Results— Morphological analysis of partially ligated carotid artery demonstrate a significant increase in neointimal area of AIF-1 Tg versus wild-type mice (569±64 um versus 256±49um, P=0.004). Immunohistochemistry using antibody to the proliferation marker Ki-67 show a significantly greater number of proliferating cells in the AIF-1 Tg lesion compared with wild-type arteries (10.6%±1.0 versus 3.6%±.9, P=0.0007). AIF-1 Tg arteries also had a greater number of cells with activated signal transduction kinase p38 (55.4%±7.0 versus 22.6%±5.4, P=0.002) and PAK1 (67.5%±6.7 versus 35.3%±10.2, P=0.02) compared with wild-type. Cultured VSMCs explanted from AIF-1 Tg proliferate (55.5±3.6x10³ versus 37.2±2.0x10³ cells/mL, P=0.0001) and migrate more rapidly (39.2±3.2 versus 17.1±1.5 VSMCs per HPF, P=0.0003) than wild-type, and have significantly greater levels of activated p38 and PAK1 than did VSMCs from wild-type littermates (P<0.05).

Conclusions— These data indicate that AIF-1 expression results in increased signal transduction, neointimal formation, and VSMC proliferation in injured mouse carotid arteries.

A transgenic mouse in which AIF-1 expression was driven by a VSMC-specific SM22 promoter was generated. Injured arteries from this mouse demonstrate a significant increase in neointimal area in response to ligation injury. In vivo and ex vivo, transgenic VSMCs demonstrate increased migration, proliferation, and activation of signal transduction proteins.

Key Words: allograft inflammatory factor-1 • carotid ligation • proliferation • signal transduction

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				Y. Tian, S. Jain, S. E. Kelemen, and M. V. Autieri AIF-1 expression regulates endothelial cell activation, signal transduction, and vasculogenesis Am J Physiol Cell Physiol, February 1, 2009; 296(2): C256 - C266. [Abstract] [Full Text] [PDF]

				L. J. Sommerville, C. Xing, S. E. Kelemen, S. Eguchi, and M. V. Autieri Inhibition of allograft inflammatory factor-1 expression reduces development of neointimal hyperplasia and p38 kinase activity Cardiovasc Res, January 1, 2009; 81(1): 206 - 215. [Abstract] [Full Text] [PDF]