Ambient particulate matter triggers dysfunction of subcellular structures and endothelial cell apoptosis through disruption of redox equilibrium and calcium homeostasis

Abstract

Ambient particulate matter (APM) is becoming a global environmental problem that seriously jeopardizes public health. Previous evidence hinted that APM correlates to cardiovascular diseases. As a potential target, equilibrium of endothelial cell is a prerequisite for vascular health which could be vulnerably attacked by particles, but the specific mechanisms whereby APM damages endothelial cells have not been fully elucidated. In the current study, based on two classical mechanisms of oxidative stress and intracellular calcium overload, we aimed to explore their roles in APM-induced endothelial cell apoptosis from the perspective of subcellular levels, including endoplasmic reticulum (ER) stress and mitochondrial dysfunction. As a result, PM SRM1648a results in oxidative stress and calcium overload in EA.hy926 cells. Additionally, ERs and mitochondria could be severely disturbed by particles in morphology and function, characterized by swelling ERs, mitochondrial fission and disappearance of cristae, coupled with ER damage, mtROS overproduction and significant reduction in mitochondrial membrane potential (MMP). Adverse effects on these organelles are the prime culprits of following apoptosis in endothelial cells. Fortunately, additional antioxidants and calcium inhibitors could mitigate cellular lesion through improvement of subcellular function. Intriguingly, antioxidants relieve cell stress via both mitochondrial and ER stress-mediated pathways, whereas the role of calcium modulators in cell apoptosis is independent of the mitochondrial pathway but could be explained by amelioration of ER stress. In conclusion, our data basically revealed that internalized PM SRM1648a triggers oxidative stress and calcium influx in EA.hy926 endothelial cells, followed by multiple subcellular damage and eventually contributes to cell death, during which antioxidants and calcium inhibitors confer protective effects.