García-Ramírez Marta, Martínez-González José, Juan-Babot Josep O, Rodríguez Cristina, Badimon Lina
Centro de Investigación Cardiovascular, CSIC/ICCC, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Arterioscler Thromb Vasc Biol. 2005 Nov;25(11):2398-403. doi: 10.1161/01.ATV.0000187464.81959.23. Epub 2005 Sep 22.
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.
SOX18是SOX基因家族（SRY样3-羟基-3-甲基戊二酰辅酶A盒基因）的成员之一，是一种在胚胎发育过程中血管生成时表达的转录因子。我们分析了SOX18在人类冠状动脉粥样硬化病变中的表达，并研究了其在血管细胞中的潜在功能。
在晚期人类冠状动脉粥样硬化病变中，SOX18免疫染色定位于内皮细胞（在管腔表面、血管滋养管和内膜新生血管中）以及散在于内膜中的血管平滑肌细胞（VSMC），并与增殖细胞核抗原共定位。在细胞培养中，SOX18主要定位于亚汇合和裸露区域。通过Northern印迹分析和逆转录-聚合酶链反应在人脐静脉内皮细胞和人VSMC的细胞培养物中检测到显著的SOX18 mRNA水平。反义SOX18抑制DNA合成（[3H]胸苷掺入）和血管细胞生长。在伤口修复的体外模型中，反义SOX18还显著减少了损伤后VSMC的再生长。
我们的结果表明SOX18参与血管细胞生长，并提示该转录因子可能在动脉粥样硬化中起作用。
