Project 2
Molecular and cellular mechanisms of cardiometabolic toxicity of VOCs
Sidebar
Studies in Project 2 are designed to:
- develop mechanistically validated biomarkers of exposure and biomarkers of harm which could be used to assess VOC-induced biomarkers on exposure and harm in our population-based study;
- test the plausibility that individual VOC exposure is sufficient to induce/exacerbate cardiometabolic disease; and
- delineate the molecular mechanisms of VOC-induced cardiometabolic toxicity.
Project 2’s previous studies showed that exposure to VOCs like benzene, xylene, and acrolein causes cardiovascular dysfunction due to damage to the cells lining the blood vessels. Studies in Year 7 found that benzene metabolites make these cells more permeable. Another study using single cell RNA sequencing on blood vessels of benzene-exposed mice showed increased inflammation, particularly an increase in T-cells in plaques. Bioinformatic studies indicate that benzene exposure causes T-cells to shift towards types that promote plaque formation and increases certain gene expressions and T-cell signaling. CellChat analysis suggests that benzene disrupts certain signaling between T-cells in plaques and other cell types like macrophages, VSMCs, and fibroblasts, and increases communication between lymphatic endothelial cells and T-cells in plaques.
Overall, increased permeability due to benzene exposure can lead to vascular inflammation, and more T-cells and disrupted T-cell signaling can trigger events that destabilize plaques and make them more susceptible to rupture.