Increased smooth muscle cell activation and neointima formation in response to injury in AIF-1 transgenic mice.
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 SM22alpha promoter was generated to establish a direct relationship between AIF-1 expression and intimal hyperplasia.


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+/-49 um, 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+/-3.6x10(3) versus 37.2+/-2.0x10(3) 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.
Sommerville
Laura J
LJ
Department of Physiology, Independence Blue Cross Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Kelemen
Sheri E
SE
Autieri
Michael V
MV
D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000502:physiology*; D002339:Carotid Arteries / Q000503:physiopathology; D002340:Carotid Artery Diseases / Q000503:physiopathology*; D049109:Cell Proliferation; D004195:Disease Models, Animal; D006965:Hyperplasia; D051379:Mice; D008822:Mice, Transgenic; D008840:Microfilament Proteins; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000502:physiology*; D011401:Promoter Regions, Genetic; D015398:Signal Transduction; D017539:Tunica Intima / Q000293:injuries / Q000473:pathology* / Q000503:physiopathology
C491049:Aif1 protein, mouse; D002135:Calcium-Binding Proteins; D008840:Microfilament Proteins