Department of Cardiology, The First Affiliated Hospital of Guangdong Pharmaceutical University.
Department of Liver Disease, Shenzhen Hospital Affiliated to Guangzhou University of Chinese Medicine.
Biosci Trends. 2018 Jul 17;12(3):282-290. doi: 10.5582/bst.2018.01063. Epub 2018 Jun 28.
The migration and invasion of vascular smooth muscle cells (VSMCs) caused by advanced aging play an important role in diffuse intimal thickening, facilitate adverse arterial remodeling and contribute to the initiation and progression of cardiovascular diseases. The inhibitory function of Buyang Huanwu decoction (BYHWD) has been found on aortic intimal hyperplasia and VSMC proliferation, but its effect on age-associated migration and invasion remains unknown. Here, we used an in vitro angiotensin II (Ang II)-induced senescence model to study the effects of serum containing BYHWD (BYHWS) on the migratory and invasive capacities, matrix metalloprotease type 2 (MMP-2) expression and modulation of sirtuin1 (SIRT1) signaling in human aorta VSMCs (HA-VAMCs). Our results showed that BYHWS was able to inhibit Ang II-induced migration and invasion, with down-regulation of MMP-2. In addition, manipulation of SIRT1 by either over-expression or siRNA knockdown ameliorated or promoted cellular migration and invasion, respectively. Moreover, BYHWS reversed senescence-mediated decrease of SIRT1 levels and SIRT1 was required for BYHWS regulation on migration and invasion of senescent HA-VAMCs. In summary, our data demonstrated that BYHWS suppressed the migration and invasion of age-associated VSMC via an increase of the SIRT1 level, which provides novel insights for the therapy of age-associated cardiovascular diseases.
血管平滑肌细胞(VSMCs)的迁移和浸润是由衰老引起的,在弥漫性内膜增厚、促进动脉重构不良以及引发和促进心血管疾病方面发挥着重要作用。补阳还五汤(BYHWD)对主动脉内膜增生和 VSMC 增殖具有抑制作用,但对与年龄相关的迁移和浸润的作用尚不清楚。在这里,我们使用体外血管紧张素 II(Ang II)诱导的衰老模型来研究含 BYHWD 的血清(BYHWS)对人主动脉 VSMCs(HA-VAMCs)迁移和侵袭能力、基质金属蛋白酶 2(MMP-2)表达以及沉默信息调节因子 1(SIRT1)信号转导的调节作用。我们的结果表明,BYHWS 能够抑制 Ang II 诱导的迁移和侵袭,并下调 MMP-2。此外,通过过表达或 siRNA 敲低 SIRT1,分别改善或促进了细胞的迁移和侵袭。此外,BYHWS 逆转了衰老介导的 SIRT1 水平降低,并且 SIRT1 是 BYHWS 调节衰老 HA-VAMCs 迁移和侵袭所必需的。综上所述,我们的数据表明,BYHWS 通过增加 SIRT1 水平来抑制与年龄相关的 VSMC 的迁移和浸润,为治疗与年龄相关的心血管疾病提供了新的见解。