Pitavastatin maintains MAPK7 expression and alleviates angiotensin II‑induced vascular endothelial cell inflammation and injury

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.

Sex Influence on Autophagy Markers and miRNAs in Basal and Angiotensin II-Treated Human Umbilical Vein Endothelial Cells

“…Among the parameters that become different with sex, there is cell viability: in FHUVECs, there is a small but not significant decrease in cell viability, whereas in male cells, it is significantly increased. This is in line with previous HUVEC cell lines of unknown sex [51,52], but in the majority of cases, it was shown that Ang II induced viability loss in HUVEC cell lines of unknown sex (an exhaustive list of references about this point is reported in Table S3 [ [53][54][55][56][57][58][59][60][61][62][63][64][65][66]). The discrepancy could be attributed to the use of HUVEC cell lines versus the primary cultures we used, and to different methods of culture and viability determination.…”

Pitavastatin protects against neomycin-induced ototoxicity through inhibition of endoplasmic reticulum stress

“…Statins are not only applied for the therapeutics of cardiovascular diseases, but also for the treatment of neurological disorders ( Oesterle et al, 2017 ; Sanz-Cuesta and Saver, 2021 ), and lots of studies have suggested that statins have potential protective effects against sensorineural hearing loss ( Brand et al, 2011 ; Park et al, 2012 ; Fernandez et al, 2020 ; Whitlon, 2022 ). Pitavastatin (PTV) is a new-generation lipophilic statin that has been reported to exert anti-oxidative, anti-inflammatory, anti-neoplastic, and neuroprotective effects ( Kaneyuki et al, 2007 ; Gbelcová et al, 2017 ; Cui et al, 2018 ; Li and Liu, 2022 ), but the role of PTV in aminoglycoside-induced ototoxicity remains unknown.…”