Senolytics Reverse PM_2.5 - Induced Cell and Vascular Dysfunction

Area of Science:

• Environmental Health
• Cardiovascular Research
• Cellular Biology

Background:

• Fine airborne particulate matter (PM2.5) exposure is linked to cardiovascular disease and atherosclerosis.
• Mechanisms of PM2.5-induced vascular inflammation, particularly early cellular events, require further definition.

Purpose of the Study:

• To investigate the cellular mechanisms of early vascular inflammation induced by PM2.5 exposure.
• To determine if senolytic treatment can ameliorate PM2.5-induced vascular dysfunction.

Main Methods:

• C57BL/6J mice were exposed to concentrated ambient PM2.5 (CAP).
• Senescence markers (β-galactosidase activity, SASP gene expression) in peripheral blood mononuclear cells (MNCs) and endothelial progenitor cells (EPCs) were assessed.
• Senolytic treatment with Dasatinib and Quercetin (DQ) was administered.
• In vitro EPC function and in vivo endothelial activation were evaluated.

Main Results:

• CAP exposure induced endothelial activation and leukocyte recruitment in mice.
• CAP exposure led to senescence of MNCs and EPCs.
• DQ treatment reversed CAP-induced senescence and improved in vitro EPC function.
• DQ treatment reduced in vivo endothelial activation.

Conclusions:

• PM2.5 exposure contributes to early atherogenesis by inducing endothelial activation and leukocyte recruitment.
• Cellular senescence plays a role in PM2.5-induced vascular dysfunction.
• Senolytic therapy shows promise for mitigating cardiovascular risks associated with chronic PM2.5 exposure.