Cadmium contributes to atherosclerosis by affecting macrophage polarization

Area of Science:

• Environmental toxicology
• Cardiovascular pathology
• Immunology

Background:

• Chronic cadmium (Cd) exposure is linked to atherosclerosis progression, but its precise role and mechanisms are unclear.
• Atherosclerosis involves chronic inflammation and M1 macrophage polarization, which produce pro-inflammatory cytokines.
• Interleukin-6 (IL-6) is implicated in the inflammatory response within atherosclerosis.

Purpose of the Study:

• To investigate the direct role of cadmium in atherosclerosis development and plaque formation.
• To elucidate the underlying mechanisms of Cd-induced atherosclerosis, focusing on macrophage polarization and IL-6 production.
• To explore the involvement of the JAK2/STAT3 signaling pathway in Cd-mediated effects.

Main Methods:

• A case-control study was conducted to assess Cd exposure and carotid plaque occurrence.
• In vivo experiments used ApoE-/- mice fed cadmium chloride (CdCl2).
• In vitro experiments utilized RAW264.7 cells treated with CdCl2, with and without JAK2/STAT3 pathway inhibition.

Main Results:

• Cadmium exposure significantly increased plaque area, macrophage accumulation, and lipid deposition in atherosclerotic mice.
• Cd promoted M1 macrophage polarization, evidenced by increased CD86 expression and elevated production of tumor necrosis factor-α (TNF-α) and IL-6.
• The JAK2/STAT3 pathway was activated by Cd exposure, and its inhibition reversed Cd-induced M1 polarization and pro-inflammatory cytokine production.
• Effects on M2 macrophages and anti-inflammatory cytokines (IL-4, IFN-γ) were not significant.

Conclusions:

• Cadmium exposure intensifies atherosclerosis by promoting M1 macrophage polarization.
• The JAK2/STAT3 pathway is a key mediator in Cd-induced M1 polarization and subsequent IL-6 upregulation.
• Cd exposure contributes to carotid plaque formation, highlighting its atherogenic potential.