PM2.5 inducing myocardial fibrosis mediated by Ang II/ERK1/2/TGF-β₁ signaling pathway in mice model

Abstract

Objects: To discuss the influence of PM2.5 on myocardial fibrosis and related mechanism. Methods: PM2.5 particles were prepared into different concentrations of solution to drip into the mice’s trachea twice each week. The mice were divided into five groups, Blank control group (C group), NS control group (J group), high dose group (G group, 10 mg/kg), medium dose group (Z group, 5 mg/kg), and 1ow dose group (D group, 2.5 mg/kg). After 6 weeks, the myocardial fibrosis was observed by HE and Masson staining. The expression of Ang II, ERK1/2, and TGF-β1 was examined by Western Blotting (WB) and Real time PCR (RT-PCR). Results: The higher dose PM2.5 was administrated, the worse the myocardial fibrosis was in PM2.5 groups. The expression of Ang II, ERK1/2, and TGF-β1 was increased in higher dose groups in protein and mRNA level. Conclusion: 1. PM2.5 induced the cardiac fibrosis. 2. PM2.5 dripped into trachea in mice model activated the expression of Ang II, ERK1/2, and TGF-β1. The activation of renin-angiotensin system (RAS) was suggested to participate in the cardiac fibrosis induced by PM2.5.

Fine Particulate Matter Exposure Levels in Patients with Normal-Tension Glaucoma and Primary Open-Angle Glaucoma: A Population-Based Study from Taiwan

“…Vasospasm is a vascular risk factor for NTG, and it also impairs the automatic regulation of retinal circulation [ 57 , 58 ]. Experiments in mice also showed that PM 2.5 -induced TGF-β1 expression was increased at higher doses of protein and mRNA levels, a mechanism for inducing heart disease [ 14 ]. This study also revealed that compared with other glaucoma patient groups, patients with NTG have a higher prevalence of cardiovascular disease [ 57 ].…”

“…The average daily exposure is calculated by dividing the daily exposure by 24 h, and the average monthly exposure is calculated by multiplying the average daily exposure by the number of days in the month. We observed exposure to PM2.5 for a 5-year period from 2008 to 2013 to study the effects of the development of NTG or POAG, and the loss of PM2.5 during this period was relatively small [ 14 , 19 ]. We used AQMN data to estimate monthly mean PM2.5 concentrations to examine differences in exposure–response relationships between NTG and POAG.…”

“…It has been proposed that there is an association between NTG and migraine, and the two diseases have a potential common vascular cause [ 13 ]. The instillation of PM 2.5 in a mouse trachea model activated the expression of Ang II, ERK1/2, and TGF-β1, causing myocardial fibrosis [ 14 ], and also inducing apoptosis and autophagy through the PI3K/AKT/mTOR signaling pathway [ 15 ]. The expression of TGF-β and the activation of the PI3K/AKT/mTOR pathway both play a role in the pathogenesis of glaucoma [ 15 , 16 ], resulting in a progressive loss of retinal ganglion cells (RGC) [ 17 ].…”

Environmental Exposome and Atrial Fibrillation: Emerging Evidence and Future Directions

“…87 Experiments involving mice have shown a dose-dependent relationship between PM 2.5 exposure and myocardial fibrosis severity with involvement of the renin-angiotensin system via activating the expression of Ang II, ERK1/2, and TGF-β1 in cardiac tissues induced by PM 2.5 . 88,89 Human umbilical vein endothelial cells treated with PM 2.5 exhibit activation of the NLRP3 inflammasome pathway, 90,91 inducing TGF-beta1 production, collagen deposition, and fibrosis. 89,90,92 Altered NLRP3 inflammasome activity has also been shown to be increased in cardiomyocytes and lysates of atrial whole tissue of patients with AF.…”

EGCG inhibits atrial fibrosis and reduces the occurrence and maintenance of atrial fibrillation and its possible mechanisms

“…In the cellular model, with reference to the relevant literature [29] and to avoid the toxic and proliferative effects of high concentrations of Ang II on cardiac broblasts, we, therefore, chose 10 nM of Ang II in culture for 24 h to establish a cardiac broblast brosis model for subsequent drug treatment experiments. TGF-β/Smad3 is one of the classic pathways in cardiac brosis, and it has been reported [30][31][32] that Ang II can promote the expression of TGF-β1 mRNA and protein to activate the downstream Smad signaling pathway to increase the synthesis of Col I and Col . Our experimental results also showed elevated TGF-β1 and Smad3 expression and signi cant atrial brosis in the Ang II-induced group of rats.…”