PM_2.5 increases mouse blood pressure by activating toll-like receptor 3

Plenty of literature has documented that fine particulate matter (PM_2.5) exposure is related to blood pressure (BP) elevation. Vascular dysfunction is the initiation of cardiovascular diseases, such as hypertension. This thesis set out to assess the role of Toll-like receptor 3 (TLR3) in the increase in BP induced by PM_2.5.

C57BL/6 and TLR3 deficient (TLR3^-/-) male mice were randomly allocated to filtered air chamber or real-world inhaled concentrated PM_2.5 chamber. BP was evaluated using non-invasive BP recordings. After euthanasia, the aortas and small mesenteric arteries (SMAs) were isolated, and vascular tone was measured using a wire myograph. Leucocytes were detached to assess myeloid-derived suppressor cells using flow cytometry. siRNA transfection was performed to silence TLR3 expression in the human vascular endothelial cells incubated with PM_2.5. The gene expression levels of inflammation, adhesion molecules, and oxidative stress in the aortas were assessed by quantitative PCR.

Exposure to PM_2.5 increased mouse BP, and TLR3 deficiency protected against PM_2.5 exposure-induced BP increase. Additionally, the injury of vascular function in the aortas and SMAs was inhibited in TLR3^-/- mice. The intercellular adhesion molecule-1 (ICAM-1) was attenuated in TLR3^-/- mice, accompanied by the inhibition of inflammatory and oxidized genes of the aortas, such as F4/80, interleukin-6, interleukin-1 beta, and NADPH oxidase 4. In vitro, the enhanced mRNA expression of genes encoding inflammation, oxidative stress, and ICAM-1 by PM_2.5 was inhibited by TLR3 silence as well.

PM_2.5 exposure increased BP via TLR3 activation and impaired vascular function.