Wang Yu-Lin, Chen Chen-Te, Tung Che-Se, Tsai Min-Chien
Center of General Education, Southern Taiwan University of Science and Technology, Tainan 710, Taiwan, R.O.C.
Department of Physical Medicine and Rehabilitation, Chi-Mei Medical Center, Tainan 710, Taiwan, R.O.C.
Exp Ther Med. 2021 May;21(5):438. doi: 10.3892/etm.2021.9855. Epub 2021 Feb 26.
Shear stress has been reported to result in various metabolic effects in endothelial cells (ECs), which in turn contribute to the regulation of their vascular functions. Peroxisome proliferator-activated receptors (PPARs) have been reported to regulate lipid metabolism and have been implicated in metabolic disorders. The present study assessed the effects of laminar shear stress on the expression of PPARs in ECs in the presence of high concentrations of free fatty acids (FFAs). Human aortic ECs (HAECs) were treated with a high concentrations of palmitic acid (PA) and exposed to high shear stress (HSS) or low shear stress (LSS). Western blotting and ELISA were performed to quantify protein expression and assess prostacyclin production. The results revealed that long-term application of HSS to PA-treated HAECs induced PPAR-α, -δ and -γ protein expression. Additionally, LSS induced higher levels of PPAR-α protein expression in PA-treated HAECs compared with those after HSS. HAECs exposed to HSS also released prostacyclin (PGI). However, HAECs treated with high concentrations of PA also produced high levels of PGI in the perfusion media in response to HSS compared with the static PA group. HSS also reduced the static PA-induced expression of intercellular adhesion molecule-1 and monocyte chemoattractant protein-1. The results demonstrated that HAECs increases the expression of all three peroxisome proliferator-activated receptor isoforms in response to shear metabolic stress at high FFA concentrations. The present study may provide preliminary insights into the potential roles of PPARs as an effective treatment method against metabolic disturbances that can result in EC dysfunction.
据报道，剪切应力可在内皮细胞（ECs）中产生多种代谢效应，进而有助于调节其血管功能。据报道，过氧化物酶体增殖物激活受体（PPARs）可调节脂质代谢，并与代谢紊乱有关。本研究评估了在高浓度游离脂肪酸（FFAs）存在的情况下，层流剪切应力对ECs中PPARs表达的影响。用人主动脉内皮细胞（HAECs）进行高浓度棕榈酸（PA）处理，并使其暴露于高剪切应力（HSS）或低剪切应力（LSS）下。采用蛋白质印迹法和酶联免疫吸附测定法来定量蛋白质表达并评估前列环素的产生。结果显示，对经PA处理的HAECs长期施加HSS可诱导PPAR-α、-δ和-γ蛋白表达。此外，与HSS处理后的情况相比，LSS诱导经PA处理的HAECs中PPAR-α蛋白表达水平更高。暴露于HSS的HAECs也释放前列环素（PGI）。然而，与静态PA组相比，经高浓度PA处理的HAECs在灌注培养基中对HSS的反应也产生了高水平的PGI。HSS还降低了静态PA诱导的细胞间黏附分子-1和单核细胞趋化蛋白-1的表达。结果表明，在高FFA浓度下，HAECs会因剪切代谢应激而增加所有三种过氧化物酶体增殖物激活受体亚型的表达。本研究可能为PPARs作为一种有效治疗方法对抗可能导致EC功能障碍的代谢紊乱的潜在作用提供初步见解。
