Atorvastatin Prevents Myocardial Fibrosis in Spontaneous Hypertension via Interleukin-6 (IL-6)/Signal Transducer and Activator of Transcription 3 (STAT3)/Endothelin-1 (ET-1) Pathway

Abstract

BackgroundHypertension is a leading global disease, and myocardial fibrosis is an important adverse effect of hypertension, seriously threatening human health. The IL-6/STAT3 pathway and endothelin-1 (ET-1) were previously suggested to play a part in myocardial fibrosis.Material/MethodsTo investigate the role of Atorvastatin (Ato) in spontaneous hypertension, systolic blood pressure (SBP) and left ventricular mass index (LVMI) were measured, and Masson trichrome staining was performed. Furthermore, the relative protein levels of the IL-6/STAT3/ET-1 pathway were tested.ResultsAto prevented myocardial fibrosis in spontaneous hypertension rats, especially at the dosage of 50 mg/kg/d. The IL-6/STAT3 pathway was observed to be suppressed by Ato, and ET-1 level in myocardial tissues was also downregulated by Ato. The phosphorylation status of STAT3 was tested after Ato treatment, showing that Ato mainly stimulated the tyr-705 phosphorylation of STAT3.ConclusionsResults of this study may help promote myocardial fibrosis therapy and provide insights into the IL-6/STAT3/ET-1-mediated mechanism in Ato-induced myocardial fibrosis inhibition.

Atorvastatin attenuates TGF‑β1‑induced fibrogenesis by inhibiting Smad3 and MAPK signaling in human ventricular fibroblasts

“…However, pre-incubation with ATV inhibited the TGF-β1-stimulated fibrotic response in hVFs. The results were in agreement with earlier studies, which reported that ATV prevents advanced glycation end products-, angiotensin II-, hypertension-, aldosterone-and doxorubicin-induced cardiac fibrosis (16)(17)(18)(19)(20).…”

“…Furthermore, statins have also been reported to possess pleiotropic cardiovascular effects, including reduced oxidative stress and inflammation, decreased platelet adhesion, improved endothelial function and enhanced atherosclerotic plaque stability (13)(14)(15). In addition, previous studies have shown that atorvastatin (ATV), a member of the statin family, exerts potential anti-myocardial fibrotic properties (16)(17)(18)(19)(20). Nevertheless, to the best of our knowledge, the molecular mechanism involved in the effect of ATV on cardiac fibrosis remains to be clarified, and limited information is available concerning the possible impact of ATV on TGF-β1-induced human ventricular fibroblast (hVF) proliferation and myofibroblast differentiation.…”

Targeting IL‐10, ZO‐1 gene expression and IL‐6/STAT‐3 trans‐signaling by a combination of atorvastatin and mesalazine to enhance anti‐inflammatory effects and attenuates progression of oxazolone‐induced colitis

“…In the current study, there was a significant activation of IL‐6/STAT‐3 signaling and treatment with mesalazine significantly decreases IL‐6 and its downstream target STAT‐3 molecule level in colon tissues and these results are in agreement with [47,48]. Also, atorvastatin strongly downregulates IL‐6/STAT‐3 signaling and these results are in the same line of other reports [49,50].…”

Effect of phenylacetamide isolated from lepidium apetalum on myocardial injury in spontaneously hypertensive rats and its possible mechanism

“…It can exert chemotaxis on neutrophils and monocytes, causing them to accumulate in the injury site and stimulate them to secrete a large number of inflammatory factors, such as interleukin-1b (IL-1b) etc. (Fang et al 2019). IL-1b can stimulate the healing of the affected area by promoting the secretion of inflammatory proteins by cells, such as monocytes, macrophages or endothelial cells (Kashyap et al 2017).…”

“…(Fang et al. 2019 ). IL-1β can stimulate the healing of the affected area by promoting the secretion of inflammatory proteins by cells, such as monocytes, macrophages or endothelial cells (Kashyap et al.…”