PDF(Pubmed)
Abstract：
Statins have been reported to suppress vascular remodeling in rats with spontaneous hypertension. However, the possible effects of the statin pitavastatin on hypertension-induced endothelial inflammation and injury remain to be fully elucidated. The present study aimed to evaluate the effects of pitavastatin on HUVEC injury and inflammation. HUVECs were exposed to angiotensin (Ang) II with or without pitavastatin co-treatment, after which MAPK7 expression was detected via reverse transcription-quantitative PCR and western blotting. MAPK7 expression was additionally silenced in HUVECs via transfection with short hairpin RNA, followed by Ang II treatment with or without pitavastatin. Cell viability, inflammation, reactive oxygen species (ROS) production, nitric oxide (NO) production and cell apoptosis were then measured by using Cell Conting Kit-8, ELISA, commercial corresponding kits and TUNEL staining, respectively. Western blotting was also used to determine the protein expression of endothelial NO synthase and endothelin 1, and the proteins involved in apoptosis. Results of the present study demonstrated that the expression levels of MAPK7 in Ang II-induced endothelial cells were decreased, which was reversed following treatment with pitavastatin. Pitavastatin reversed the Ang II-induced reduction in cell viability and reversed the Ang II-induced increase in inflammatory factor and ROS levels and apoptosis in HUVECs by activating MAPK7. Treatment with pitavastatin also increased the production of NO in addition to increasing the expression of endothelial NO synthase and endothelin-1 in Ang II-induced HUVECs through MAPK7 activation. Collectively, results from the present study demonstrated that treatment with pitavastatin preserves MAPK7 expression to alleviate Ang II-induced vascular endothelial cell inflammation and injury. Therefore, findings of the present study may help to elucidate the mechanisms underlying the effects of pitavastatin on vascular endothelial cell inflammation and injury.
摘要：
据报道，他汀类药物可抑制自发性高血压大鼠的血管重塑。然而,他汀类药物匹伐他汀对高血压诱导的内皮炎症和损伤的可能作用仍有待完全阐明。本研究旨在评价匹伐他汀对HUVEC损伤和炎症的影响。HUVEC暴露于血管紧张素（Ang）II，有或没有匹伐他汀共同治疗，之后通过逆转录定量PCR和蛋白质印迹检测MAPK7表达。MAPK7表达在HUVEC中通过短发夹RNA转染而沉默，然后用或不用匹伐他汀进行AngII治疗。细胞活力，炎症,活性氧（ROS）的产生，一氧化氮（NO）的产生和细胞凋亡，然后通过使用细胞检测试剂盒-8，ELISA，商业相应的试剂盒和TUNEL染色，分别。Western印迹还用于确定内皮NO合酶和内皮素1的蛋白表达以及参与凋亡的蛋白。本研究的结果表明，MAPK7在AngII诱导的内皮细胞中的表达水平降低，用匹伐他汀治疗后逆转。匹伐他汀通过激活MAPK7逆转了AngII诱导的细胞活力降低，逆转了AngII诱导的HUVECs炎症因子和ROS水平增加以及凋亡。匹伐他汀治疗除了通过MAPK7激活增加AngII诱导的HUVEC中内皮NO合酶和内皮素-1的表达外，还增加了NO的产生。总的来说，本研究的结果表明，匹伐他汀治疗可以保留MAPK7的表达，从而减轻AngII诱导的血管内皮细胞炎症和损伤。因此,本研究结果可能有助于阐明匹伐他汀对血管内皮细胞炎症和损伤的作用机制。
