Mu Hongmei, Wang Liyong, Zhao Lei
Department of Ultrasonography, Cangzhou Central Hospital, Cangzhou, Hebei, China.
Department of Neurology, Cangzhou People's Hospital, Cangzhou, Hebei, China.
Cardiovasc Ther. 2017 Apr;35(2). doi: 10.1111/1755-5922.12243.
Emerging evidences indicate that heat-shock protein 90 (HSP90) is associated with atherogenesis. However, the effect of HSP90 on plaque stability is largely unknown. In this study, we explored the role of HSP90 in plaque development and its regulatory mechanisms on vasculature.
Heat-shock protein90-overexpression lentivirus (Lenti-HSP90) was used to transfect apoE mice after constrictive collars were planted at the right common carotid arteries.
As a result, HSP90 gene overexpression led to reduction in en face plaque area and increase in unstable plaque with heavier accumulation of lipids. Concomitantly, more macrophages, less smooth muscle cells, and collagen were generated, suggesting aggravated inflammation. However, inhibition of HSP90 with 17-AAG, a HSP90-inhibitor, induced opposing effects. Moreover, HSP90 upregulated plaque MMP-8, which might be the underlying mechanism of the change in plaque vulnerability index. Further, the translocation of NF-κB was promoted by HSP90, while inhibition of NF-κB significantly reduced MMP-8 production, which is upregulated by HSP90.
These findings suggested that HSP90 governs plaque development and vulnerability, as well as inflammation, at least in part via MMP-8 and NF-κB signaling pathways.
新出现的证据表明，热休克蛋白90（HSP90）与动脉粥样硬化的发生有关。然而，HSP90对斑块稳定性的影响在很大程度上尚不清楚。在本研究中，我们探讨了HSP90在斑块发展中的作用及其对脉管系统的调节机制。
在apoE小鼠右侧颈总动脉植入缩窄环后，使用热休克蛋白90过表达慢病毒（Lenti-HSP90）转染小鼠。
结果显示，HSP90基因过表达导致斑块正面面积减小，不稳定斑块增加，脂质堆积更严重。同时，产生了更多的巨噬细胞、更少的平滑肌细胞和胶原蛋白，提示炎症加重。然而，用HSP90抑制剂17-AAG抑制HSP90则产生相反的效果。此外，HSP90上调斑块MMP-8，这可能是斑块易损性指数变化的潜在机制。此外，HSP90促进NF-κB的易位，而抑制NF-κB可显著降低由HSP90上调的MMP-8的产生。
这些发现表明，HSP90至少部分通过MMP-8和NF-κB信号通路控制斑块的发展、易损性以及炎症。
