Cardiovascular Research Center, Temple University School of Medicine, 3500 N Broad Street, Philadelphia, PA 19140, USA.
Atherosclerosis. 2013 May;228(1):90-3. doi: 10.1016/j.atherosclerosis.2013.02.033. Epub 2013 Mar 13.
The Max-interacting protein Mnt is a transcriptional repressor that can antagonize the transcriptional and proliferation-related activities of Myc. Here, we tested the hypothesis that Mnt is a negative regulator of pathological vascular remodeling.
Adenovirus encoding Mnt or control GFP was infected to cultured rat vascular smooth muscle cells (VSMC) and carotid arteries after a balloon angioplasty.
In VSMC, adenoviral gene transfer of Mnt suppressed angiotensin II-induced protein expression of early growth response protein-1 (Egr1) and its promoter activation. Mnt adenovirus did not interfere with upstream signaling of angiotensin II. Angiotensin II-induced protein accumulation in VSMC was inhibited by Mnt adenovirus. Mnt adenovirus also inhibited platelet-derived growth factor-induced VSMC proliferation. Moreover, Mnt adenovirus prevented neointima formation in response to arterial injury. The adenoviral Mnt gene transfer also prevented Egr1 induction in neointima.
These data identify Mnt as a previously unrecognized negative regulator of pathological vascular remodeling.
Max 相互作用蛋白 Mnt 是一种转录阻遏物，可拮抗 Myc 的转录和增殖相关活性。在这里，我们检验了 Mnt 是病理性血管重构的负调控因子这一假说。
在球囊血管成形术后，将编码 Mnt 或对照 GFP 的腺病毒感染到培养的大鼠血管平滑肌细胞（VSMC）和颈动脉中。
在 VSMC 中，Mnt 的腺病毒基因转移抑制了血管紧张素 II 诱导的早期生长反应蛋白-1（Egr1）及其启动子激活的蛋白表达。Mnt 腺病毒不干扰血管紧张素 II 的上游信号。Mnt 腺病毒抑制血管紧张素 II 诱导的 VSMC 蛋白积累。Mnt 腺病毒还抑制血小板衍生生长因子诱导的 VSMC 增殖。此外，Mnt 腺病毒可防止动脉损伤后的新生内膜形成。腺病毒 Mnt 基因转移也可防止新生内膜中 Egr1 的诱导。
这些数据表明 Mnt 是病理性血管重构的一个以前未被识别的负调控因子。
