Effects of genetic ablation of bach1 upon smooth muscle cell proliferation and atherosclerosis after cuff injury
Effects of genetic ablation of bach1 upon smooth muscle cell proliferation and atherosclerosis after cuff injury
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DOI：
10.1111/j.1365-2443.2005.00832.x
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发表时间：
2005-03-01
期刊：
影响因子：
2.1
通讯作者：
Igarashi, K
中科院分区：
文献类型：
--
作者：
Omura, S;Suzuki, H;Igarashi, K
Bach 1是细胞保护酶血红素加氧酶-1（HO-1）的转录抑制因子。虽然HO-1可以预防动脉粥样硬化，但Bach 1在这一过程中的功能知之甚少。我们从野生型和bach 1缺陷小鼠中分离出腹腔巨噬细胞和主动脉平滑肌细胞（SMC）。当与0.75 μ m微球孵育时，bach 1缺陷型巨噬细胞表达增加的HO-1水平，并显示出升高的吞噬活性。在SMC中，与野生型细胞相比，bach 1-消融导致HO-1表达增加，溴脱氧尿苷掺入试验中增殖降低。上调的吞噬活性和减少SMC增殖的Bach 1缺陷细胞没有恢复锌（II）原卟啉IX，HO的抑制剂，这表明HO-独立的机制也参与调节巨噬细胞的吞噬和SMC增殖的Bach 1。在野生型小鼠中，股动脉周围的袖带放置引起明显的内膜增生，而不影响中膜，因此导致内膜与中膜（I/M）体积比为65.6%。bach 1缺陷小鼠的内膜生长程度较低（I/M比为45.6%）。这些结果表明Bach 1在HO-1表达、巨噬细胞功能、SMC增殖和新生内膜形成的调节中起关键作用。Bach 1可能在炎症和动脉粥样硬化形成过程中调节这些细胞中的基因表达。
Bach1 is a transcriptional repressor of the cytoprotective enzyme heme oxygenase-1 (HO-1). Although HO-1 protects against atherosclerosis, the function of Bach1 in this process is poorly understood. We isolated peritoneal macrophages and aortic smooth muscle cells (SMC) from wild-type and bach1-deficient mice. bach1-deficient macrophages expressed increased levels of HO-1 and showed elevated phagocytic activity when incubated with 0.75 mum microspheres. In SMC, bach1-ablation resulted in increased expression of HO-1 and decreased proliferation in bromodeoxyuridine incorporation assay as compared with wild-type cells. The up-regulated phagocytic activity and reduced SMC proliferation of bach1-deficient cells were not restored by Zinc (II) protoporphyrin IX, an inhibitor of HO, suggesting that HO-independent mechanisms are also involved in the regulation of phagocytosis of macrophages and proliferation of SMC by Bach1. In wild-type mice, cuff placement around femoral artery caused pronounced intimal proliferation without affecting the media, thus resulting in intimal to medial (I/M) volume ratio of 65.6%. bach1-deficient mice had less degree of intimal growth (I/M ratio of 45.6%). These results indicate that Bach1 plays a critical role in the regulation of HO-1 expression, macrophage function, SMC proliferation and neointimal formation. Bach1 may regulate gene expression in these cells during inflammation and atherogenesis.