Activating transcription factor 3 regulates survivability and migration of vascular smooth muscle cells.

Activating transcription factor 3 (ATF3) is a member of the ATF/CREB (CAMP responsive element binding protein) family of transcription factors. The expression and the function of ATF3 in vascular smooth muscle cells (VSMCs) remain unknown. The aim of this work is to determine the expression and possible function of ATF3 in VSMCs. We found that VSMCs expressed ATF3, and expression of ATF3 in VSMCs was induced by a variety of stimuli including serum, angiotensin II, and H(2)O(2). Knockdown of ATF3 induced apoptosis of VSMCs, caspase-3 cleavage, and cytochrome c release. The results suggest that ATF3 regulates survivability of VSMCs. Moreover, we found that overexpression of ATF3 promoted migration of VSMCs and induced expression of matrix metalloproteinase 1, 3, and 13. These results suggest that ATF3 plays a role in regulating migration of VSMCs. In addition, we found that the expression of ATF3 was upregulated in smooth muscle cells in the injured mouse femoral arteries compared with the uninjured control group. These results suggest that ATF3 is relevant to disease physiology.