Rani Kaliyaperumal, Aung Nway Y
Nanyang Technological University Singapore, Singapore.
Open Biochem J. 2017 Jun 30;11:56-65. doi: 10.2174/1874091X01711010056. eCollection 2017.
Vascular Smooth Muscle cells (VSMC) enact crucial roles in early vasculogenesis and sustenance of vascular integrity. However, aberrant proliferation of VSMC followed by migration into the blood vessel wall leads to the formation of vascular lesions accounting for the degeneration and remodelling of vascular basement membrane. In diabetes, hyperglycaemia accelerates VSMC proliferation and contributes to the initiation and progression of atherosclerotic lesions. Recently, acute glucose fluctuations have been implicated in the abnormal VSMC proliferation and complications of diabetic atherosclerosis. Docosahexaenoic acid (DHA), a ω-3 polyunsaturated fatty acid (PUFA) has been shown to inhibit proliferation of several cell types implicating several different mechanisms. In the present study, we have investigated the effects of DHA on VSMC proliferation induced by stable and intermittent high glucose levels.
Confluent cultures of rat aortic VSMCs were treated with DHA for 24 hrs and then exposed to stable high glucose (25 mmol/L, SHG) or intermittent high glucose (5 mmol/L and 25 mmol/L alternating every 12 hrs, IHG) for 72 hrs. Cell proliferation was examined by the MTT viability assay, while apoptosis process was evaluated by the Hoechst staining, flow cytometry and caspase-3 activity assays.
Our data demonstrated that the hyper proliferation induced by stable and intermittent high glucose levels was significantly inhibited by the DHA pre-treatment. DHA significantly increased caspase-3 activity, resulting in enhanced DNA fragmentation and apoptosis.
Our results suggest that DHA reduced the high glucose-induced proliferation of VSMC and induced cell apoptosis.
血管平滑肌细胞（VSMC）在早期血管生成和维持血管完整性方面发挥着关键作用。然而，VSMC异常增殖并迁移到血管壁会导致血管病变的形成，这是血管基底膜退变和重塑的原因。在糖尿病中，高血糖会加速VSMC增殖，并促进动脉粥样硬化病变的发生和发展。最近，急性血糖波动与VSMC异常增殖及糖尿病动脉粥样硬化并发症有关。二十二碳六烯酸（DHA），一种ω-3多不饱和脂肪酸（PUFA），已被证明可通过多种不同机制抑制多种细胞类型的增殖。在本研究中，我们研究了DHA对稳定和间歇性高糖水平诱导的VSMC增殖的影响。
将汇合的大鼠主动脉VSMC培养物用DHA处理24小时，然后暴露于稳定高糖（25 mmol/L，SHG）或间歇性高糖（5 mmol/L和25 mmol/L每12小时交替一次，IHG）中72小时。通过MTT活力测定法检测细胞增殖，同时通过Hoechst染色、流式细胞术和caspase-3活性测定法评估凋亡过程。
我们的数据表明，DHA预处理可显著抑制稳定和间歇性高糖水平诱导的过度增殖。DHA显著增加caspase-3活性，导致DNA片段化增强和细胞凋亡。
我们的结果表明，DHA可降低高糖诱导的VSMC增殖并诱导细胞凋亡。
