Li Volti Giovanni, Wang Jishi, Traganos Frank, Kappas Attallah, Abraham Nader G
Department of Medicine, New York Medical College, 10595, Valhalla, NY, USA.
Biochem Biophys Res Commun. 2002 Sep 6;296(5):1077-82. doi: 10.1016/s0006-291x(02)02054-5.
Arterial remodeling in response to pathological insult is a complex process that depends in part on the balance between vascular cell apoptosis and proliferation. Studies in experimental models suggest that HO-1 mediates neointimal formation while limiting lumen stenosing, indicating a differential effect on vascular endothelial (EC) and smooth muscle cells (SMC). We investigated the effect of HO-1 expression on cell cycle progression in EC and SMC. The addition of SnMP (10 microM), an inhibitor of HO activity, to EC or SMC for 24h, resulted in significant abnormalities in DNA distribution and cell cycle progression compared to cells treated with the HO-1 inducers, heme (10 microM) or SnCl(2) (10 microM). SnMP increased G(1) phase and decreased S and G(2)/M phases in EC while heme or SnCl(2) decreased G(1) phase, but increased S and G(2)/M phases (p<0.05). Opposite effects were obtained in SMC. SnMP decreased G(1) phase and increased S and G(2)/M phases while heme or SnCl(2) increased G(1) phase but decreased S and G(2)/M phases (p<0.05). Our data demonstrate that HO-1 regulates the cell cycle in a cell-specific manner; it increases EC but decreases SMC cycle progression. The mechanisms underlying the HO-1 cell-specific effect on cell cycle progression within the vascular wall are yet to be explored. Nevertheless, these findings suggest that cell-specific targeting of HO-1 expression may provide a novel therapeutic strategy for the treatment of cardiovascular diseases.
动脉对病理性损伤的重塑是一个复杂的过程，部分取决于血管细胞凋亡与增殖之间的平衡。实验模型研究表明，HO-1介导内膜形成，同时限制管腔狭窄，这表明其对血管内皮细胞（EC）和平滑肌细胞（SMC）具有不同的作用。我们研究了HO-1表达对EC和SMC细胞周期进程的影响。与用HO-1诱导剂血红素（10 microM）或氯化亚锡（10 microM）处理的细胞相比，向EC或SMC中添加HO活性抑制剂SnMP（10 microM）24小时，导致DNA分布和细胞周期进程出现明显异常。SnMP使EC中的G1期增加，S期和G2/M期减少，而血红素或氯化亚锡使G1期减少，但增加S期和G2/M期（p<0.05）。在SMC中获得了相反的结果。SnMP使G1期减少，S期和G2/M期增加，而血红素或氯化亚锡使G1期增加，但减少S期和G2/M期（p<0.05）。我们的数据表明，HO-1以细胞特异性方式调节细胞周期；它增加EC的细胞周期进程，但减少SMC的细胞周期进程。HO-1对血管壁内细胞周期进程的细胞特异性作用的机制尚待探索。然而，这些发现表明，细胞特异性靶向HO-1表达可能为心血管疾病的治疗提供一种新的治疗策略。
