Dataset Information

TGF-β-Containing Small Extracellular Vesicles From PM_2.5-Activated Macrophages Induces Cardiotoxicity.

ABSTRACT: Numerous epidemiological and experimental studies have demonstrated that the exposure to fine particulate matter (aerodynamic diameter <2.5 μm, PM_2.5) was closely associated with cardiovascular morbidity and mortality. Our previous studies revealed that PM_2.5 exposure induced cardiac dysfunction and fibrosis. However, the corresponding underlying mechanism remains largely unaddressed. Here, PM_2.5-induced cardiotoxicity is presented to directly promote collagen deposition in cardiomyocytes through the transforming growth factor-β (TGF-β)-containing small extracellular vesicles (sEV). The sEV transition may play an important role in PM_2.5-induced cardiac fibrosis. Firstly, long-term PM_2.5 exposure can directly induce cardiac fibrosis and increase the level of serum sEV. Secondly, PM_2.5 can directly activate macrophages and increase the release of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and TGF-β-containing sEV. Thirdly, TGF-β-containing sEV increases the expression of α-smooth muscle actin (α-SMA), collagen I, and collagen III in mouse cardiac muscle HL-1 cells. Finally, TGF-β-containing sEV released from PM_2.5-treated macrophages can increase collagen through the activation of the TGF-β-Smad2/3 signaling pathway in HL-1 cells from which some fibroblasts involved in cardiac fibrosis are thought to originate. These findings suggest that TGF-β-containing sEV from PM_2.5-activated macrophages play a critical role in the process of increasing cardiac collagen content via activating the TGF-β-Smad2/3 signaling pathway.

SUBMITTER: Hu X

PROVIDER: S-EPMC9304575 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

TGF-β-Containing Small Extracellular Vesicles From PM2.5-Activated Macrophages Induces Cardiotoxicity.

Hu Xiaoqi X Chen Mo M Cao Xue X Yuan Xinyi X Zhang Fang F Ding Wenjun W

Frontiers in cardiovascular medicine 20220708

Numerous epidemiological and experimental studies have demonstrated that the exposure to fine particulate matter (aerodynamic diameter <2.5 μm, PM2.5) was closely associated with cardiovascular morbidity and mortality. Our previous studies revealed that PM2.5 exposure induced cardiac dysfunction and fibrosis. However, the corresponding underlying mechanism remains largely unaddressed. Here, PM2.5-induced cardiotoxicity is presented to directly promote collagen de ...[more]

PMID: 35872905

Similar Datasets

Project description:Air pollution, via ambient PM2.5, is a big threat to public health since it associates with increased hospitalisation, incidence rate and mortality of cardiopulmonary injury. However, the potential mediators of pulmonary injury in PM2.5 -induced cardiovascular disorder are not fully understood. To investigate a potential cross talk between lung and heart upon PM2.5 exposure, intratracheal instillation in vivo, organ culture ex vivo and human bronchial epithelial cells (Beas-2B) culture in vitro experiments were performed respectively. The exposed supernatants of Beas-2B were collected to treat primary neonatal rat cardiomyocytes (NRCMs). Upon intratracheal instillation, subacute PM2.5 exposure caused cardiac dysfunction, which was time-dependent secondary to lung injury in mice, thereby demonstrating a cross-talk between lungs and heart potentially mediated via small extracellular vesicles (sEV). We isolated sEV from PM2.5 -exposed mice serum and Beas-2B supernatants to analyse the change of sEV subpopulations in response to PM2.5 . Single particle interferometric reflectance imaging sensing analysis (SP-IRIS) demonstrated that PM2.5 increased CD63/CD81/CD9 positive particles. Our results indicated that respiratory system-derived sEV containing miR-421 contributed to cardiac dysfunction post-PM2.5 exposure. Inhibition of miR-421 by AAV9-miR421-sponge could significantly reverse PM2.5 -induced cardiac dysfunction in mice. We identified that cardiac angiotensin converting enzyme 2 (ACE2) was a downstream target of sEV-miR421, and induced myocardial cell apoptosis and cardiac dysfunction. In addition, we observed that GW4869 (an inhibitor of sEV release) or diminazene aceturate (DIZE, an activator of ACE2) treatment could attenuate PM2.5 -induced cardiac dysfunction in vivo. Taken together, our results suggest that PM2.5 exposure promotes sEV-linked miR421 release after lung injury and hereby contributes to PM2.5 -induced cardiac dysfunction via suppressing ACE2.

Project description:IntroductionDespite the London Underground (LU) handling on average 2.8 million passenger journeys per day, the characteristics and potential health effects of the elevated concentrations of metal-rich PM2.5 found in this subway system are not well understood.MethodsSpatial monitoring campaigns were carried out to characterise the health-relevant chemical and physical properties of PM2.5 across the LU network, including diurnal and day-to-day variability and spatial distribution (above ground, depth below ground and subway line). Population-weighted station PM2.5 rankings were produced to understand the relative importance of concentrations at different stations and on different lines.ResultsThe PM2.5 mass in the LU (mean 88 μg m-3, median 28 μg m-3) was greater than at ambient background locations (mean 19 μg m-3, median 14 μg m-3) and roadside environments in central London (mean 22 μg m-3, median 14 μg m-3). Concentrations varied between lines and locations, with the deepest and shallowest submerged lines being the District (median 4 μg m-3) and Victoria (median 361 μg m-3 but up to 885 μg m-3). Broadly in agreement with other subway systems around the world, sampled LU PM2.5 comprised 47% iron oxide, 7% elemental carbon, 11% organic carbon, and 14% metallic and mineral oxides. Although a relationship between line depth and air quality inside the tube trains was evident, there were clear influences relating to the distance from cleaner outside air and the exchange with cabin air when the doors open. The passenger population-weighted exposure analysis demonstrated a method to identify stations that should be prioritised for remediation to improve air quality.ConclusionPM2.5 concentrations in the LU are many times higher than in other London transport Environments. Failure to include this environment in epidemiological studies of the relationship between PM2.5 and health in London is therefore likely to lead to a large exposure misclassification error. Given the significant contribution of underground PM2.5 to daily exposure, and the differences in composition compared to urban PM2.5, there is a clear need for well-designed studies to better understand the health effects of underground exposure.

Dataset Information

TGF-β-Containing Small Extracellular Vesicles From PM_2.5-Activated Macrophages Induces Cardiotoxicity.

Publications

TGF-β-Containing Small Extracellular Vesicles From PM<sub>2.5</sub>-Activated Macrophages Induces Cardiotoxicity.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets