PM2.5 induces vascular permeability increase through activating MAPK/ERK signaling pathway and ROS generation
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Published on: December 21, 2011
Yan-Min Long1, Xue-Zhi Yang2, Qing-Qing Yang1
1Hubei Key Laboratory of Environmental and Health Effects of Persistent Toxic Substances, Institute of Environment and Health, Jianghan University, Wuhan, Hubei 430056, China.
Abstract:
Although in-vivo exposure of PM2.5 has been suggested to initiate a disorder on vascular permeability, the effects and related mechanism has not been well defined. In this work, an obvious increase on vascular permeability has been confirmed in vivo by vein injection of PM2.5 into Balb/c mouse. Human umbilical vein vascular endothelial cells and the consisted ex-vivo vascular endothelium were used as model to investigate the effects of PM2.5 on the vascular permeability and the underlying molecular mechanism. Upon PM2.5 exposure, the vascular endothelial growth factor receptor 2 on cell membrane phosphorylates and activates the downstream mitogen-activated protein kinase (MAPK)/ERK signaling. The adherens junction protein VE-cadherin sheds and the intercellular junction opens, damaging the integrity of vascular endothelium via paracellular pathway. Besides, PM2.5 induces the intracellular reactive oxygen species (ROS) production and triggers the oxidative stress including activity decrease of superoxide dismutase, lactate dehydrogenase release and permeability increase of cell membrane. Taken together, the paracellular and transcellular permeability enhancement jointly contributes to the significant increase of endothelium permeability and thus vascular permeability upon PM2.5 exposure. This work provides an insight into molecular mechanism of PM2.5 associated cardiovascular disease and offered a real-time screening method for the health risk of PM2.5.
Insights
Fine particulate matter (PM2.5) exposure increases vascular permeability by damaging endothelial cells. This study reveals PM2.5 triggers oxidative stress and disrupts cell junctions, impacting cardiovascular health.
Area of Science:
- Environmental Health
- Toxicology
- Cardiovascular Biology
Background:
- Particulate matter (PM2.5) exposure is linked to vascular permeability disorders, but mechanisms remain unclear.
- Understanding PM2.5's effects on vascular integrity is crucial for public health.
- Existing research lacks detailed molecular insights into PM2.5-induced vascular damage.
Purpose of the Study:
- To investigate the in vivo and in vitro effects of PM2.5 on vascular permeability.
- To elucidate the molecular mechanisms underlying PM2.5-induced vascular endothelial damage.
- To establish a screening method for assessing PM2.5 health risks.
Main Methods:
- In vivo studies using PM2.5 vein injection in Balb/c mice.
- In vitro studies with human umbilical vein vascular endothelial cells and ex vivo endothelium.
- Analysis of VEGFR2 phosphorylation, MAPK/ERK signaling pathway activation.
- Assessment of VE-cadherin shedding, intercellular junction integrity, and oxidative stress markers (ROS, SOD, LDH).
Main Results:
- PM2.5 exposure significantly increased vascular permeability in vivo.
- PM2.5 activated VEGFR2 and MAPK/ERK signaling, leading to VE-cadherin shedding and opening of intercellular junctions.
- PM2.5 induced oxidative stress, evidenced by increased ROS production and decreased superoxide dismutase activity.
- Cell membrane integrity was compromised, indicated by lactate dehydrogenase release.
Conclusions:
- PM2.5 exposure enhances both paracellular and transcellular permeability, leading to increased vascular permeability.
- The study elucidates the molecular pathways involving oxidative stress and cell junction disruption.
- Findings offer insights into PM2.5-associated cardiovascular disease mechanisms and a potential screening tool for health risks.
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