Oxidative stress produced with cell migration increases synthetic phenotype of vascular smooth muscle cells
Oxidative stress produced with cell migration increases synthetic phenotype of vascular smooth muscle cells
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DOI：
10.1007/s10439-005-7545-2
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发表时间：
2005-11-01
影响因子：
3.8
通讯作者：
McIntire, LV
中科院分区：
文献类型：
--
作者：
Sung, HJ;Eskin, SG;McIntire, LV
血管平滑肌细胞（VSMC）和活性氧（ROS）的表型调节在血管发病机制中具有重要意义。了解这些因素与细胞迁移的关系可以改善控制血管疾病的治疗干预措施的设计。我们比较了野生型（WT）与转基因小鼠（Tgp 22 phox）培养的主动脉VSMC的增殖，蛋白质含量和迁移，其中p22 phox的过表达针对VSMC。此外，我们在体外创伤划痕模型中比较了H2 O2的产生和非迁移性WT与迁移性WT与Tgp 22 phox VSMC的特异性表型标记物的表达。与WT VSMC相比，Tgp 22 phox中H2 O2产生的增加（p < 0.005）与蛋白含量、增殖和迁移的增加显著相关。移行的VSMC比非移行的VSMC产生更多的H2 O2（p < 0.05）。合成表型标记物原肌球蛋白4和肌球蛋白重链胚胎（SMemb）的表达在迁移细胞与非迁移细胞中显著增强，而收缩标记物平滑肌α-肌动蛋白的表达在迁移细胞与非迁移细胞中显著降低，并且在Tgp 22 phox与WT VSMC中也显著降低（p < 0.005）。这些结果与ROS产生增加加速从收缩表型向合成表型的转换一致，其特征在于增殖、迁移和TM 4和SMemb表达增加以及α-肌动蛋白减少。
Phenotypic modulation of vascular smooth muscle cells (VSMC) and reactive oxygen species (ROS) is important in vascular pathogenesis. Understanding how these factors relate to cell migration can improve design of therapeutic interventions to control vascular disease. We compared the proliferation, protein content and migration of cultured aortic VSMC from wild type (WT) versus transgenic mice (Tgp22phox), in which overexpression of p22phox was targeted to VSMC. Also, we compared H2O2 generation and expression of specific phenotypic markers of non-migrating with migrating WT versus Tgp22phox VSMC in an in vitro wound scratch model. Enhanced H2O2 production in Tgp22phox versus WT VSMC (p < 0.005) significantly correlated with increased protein content, proliferation, and migration. VSMC migrating across the wound edge produced more H2O2 than non-migrating VSMC (p < 0.05). The expression of synthetic phenotypic markers, tropomyosin 4 and myosin heavy chain embryonic (SMemb), was enhanced significantly, while the expression of contractile marker, smooth muscle alpha-actin, was reduced significantly in migrating versus non-migrating cells, and also in Tgp22phox versus WT (p < 0.005) VSMC. These results are consistent with increased production of ROS accelerating the switch from the contractile to the synthetic phenotype, characterized by increases in proliferation, migration, and expression of TM4 and SMemb and decreased alpha-actin.