Sukketsiri Wanida, Tipmanee Varomyalin, Rungruang Panlekha, Higashihara Mayo, Sumi Tomoko, Moriyama Tatsuya, Zaima Nobuhiro
Division of Health and Applied Sciences, Faculty of Science, Prince of Songkla University, Songkhla, Thailand.
Department of Biomedical Sciences, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand.
Adv Pharmacol Pharm Sci. 2024 Nov 26;2024:9076988. doi: 10.1155/adpp/9076988. eCollection 2024.
ER stress is a crucial factor in the progression of vascular cell diseases. Notably, octanoic acid (OA; C8:0) and decanoic acid (DA; C10:0), prominent components of medium-chain fatty acids (MCFAs), may provide potential health benefits. However, their effects on vascular smooth muscle cells (VSMCs) remain unknown. Given the link between ER stress and vascular cell pathological conditions, the primary goal of this research is to investigate the protective effects of OA and DA against ER stress induction in rat aortic smooth muscle cells (RASMCs). To achieve this objective, RASMCs were pretreated with OA and DA at concentrations of 250 and 500 μM for 24 h. Subsequently, the cells were exposed to 1 μg/mL of tunicamycin, an ER stress inducer, for an additional 24 h. Apoptosis was assessed using DAPI staining, while DCFH-DA probe was used to measure ROS levels. Furthermore, the gene expression of ER stress markers, such as , , , and , as well as contractile markers like and , was assessed using real-time reverse transcription polymerase chain reaction. Moreover, the SMA protein level was measured using immunocytochemistry techniques. The study revealed that OA and DA significantly mitigated cell death caused by tunicamycin, decreased ROS production, and inhibited the gene expression of ER stress markers (, , and ). Notably, OA and DA also inhibited the expression of contractile genes ( and ) and reduced the number of -SMA-positive cells in tunicamycin-treated RASMCs. These findings indicate that OA and DA offer protection against ER stress-stimulated cell death and ROS generation in VSMCs, thereby supporting their potential therapeutic applications for safeguarding these cells.
内质网应激是血管细胞疾病进展中的一个关键因素。值得注意的是，辛酸（OA；C8:0）和癸酸（DA；C10:0）是中链脂肪酸（MCFAs）的主要成分，可能具有潜在的健康益处。然而，它们对血管平滑肌细胞（VSMCs）的影响尚不清楚。鉴于内质网应激与血管细胞病理状况之间的联系，本研究的主要目标是研究OA和DA对大鼠主动脉平滑肌细胞（RASMCs）内质网应激诱导的保护作用。为实现这一目标，将RASMCs用浓度为250和500μM的OA和DA预处理24小时。随后，将细胞再暴露于1μg/mL的衣霉素（一种内质网应激诱导剂）中24小时。使用DAPI染色评估细胞凋亡，同时使用DCFH-DA探针测量活性氧水平。此外，使用实时逆转录聚合酶链反应评估内质网应激标志物（如 、 、 、 ）以及收缩标志物（如 和 ）的基因表达。此外，使用免疫细胞化学技术测量平滑肌肌动蛋白（SMA）蛋白水平。研究表明，OA和DA显著减轻了衣霉素引起的细胞死亡，降低了活性氧的产生，并抑制了内质网应激标志物（ 、 、 ）的基因表达。值得注意的是，OA和DA还抑制了收缩基因（ 和 ）的表达，并减少了衣霉素处理的RASMCs中SMA阳性细胞的数量。这些发现表明，OA和DA可保护VSMCs免受内质网应激刺激的细胞死亡和活性氧生成，从而支持它们在保护这些细胞方面的潜在治疗应用。
