Transcription Factor SOX18 Is Expressed in Human Coronary Atherosclerotic Lesions and Regulates DNA Synthesis and Vascular Cell Growth

Abstract

SOX18, a member of the SOX gene family (SRY-like 3-hydroxy-3-methylglutaryl box gene), is a transcription factor expressed in the development of blood vessels during embryogenesis. We analyzed SOX18 expression in human coronary atherosclerotic lesions and investigated its potential function in vascular cells. In advanced human coronary atherosclerotic lesions, SOX18 immunostaining was localized in endothelial cells (on the luminal surface, in vasa vasorum, and in intimal neovessels) and in vascular smooth muscle cells (VSMCs) scattered in the intima, colocalizing with proliferating cell nuclear antigen. In cell cultures, SOX18 was mainly localized in subconfluent and denuded areas. Significant SOX18 mRNA levels (by Northern blot analysis and reverse transcription-polymerase chain reaction) were detected in cell cultures from human umbilical vein endothelial cells and human VSMCs. Antisense SOX18 inhibited DNA synthesis ([3H]thymidine incorporation) and vascular cell growth. Antisense SOX18 also significantly reduced VSMC regrowth after injury in an in vitro model of wound repair. Our results indicate that SOX18 is involved in vascular cell growth and suggest that this transcription factor may play a role in atherosclerosis.