Glyphosate Causes Vascular Toxicity through Cellular Senescence and Lipid Accumulation

Area of Science:

• Toxicology
• Cardiovascular Biology
• Cell Biology

Background:

• Glyphosate (GLY) is a widely used herbicide with increasing attention on its health risks.
• Potential vascular toxic effects of GLY, especially in occupationally exposed populations, are not well understood.

Purpose of the Study:

• To investigate the vascular toxic effects of GLY on human aortic vascular smooth muscle cells (HAVSMCs).
• To explore the relationship between GLY exposure and the development of atherosclerosis.

Main Methods:

• Assessed GLY effects on HAVMC morphology, senescence markers (β-galactosidase, p53, p21, p16), and cellular damage (ROS, DNA, mitochondria).
• Investigated the Nrf2-Keap1 pathway activation in response to GLY-induced oxidative stress.
• Utilized a zebrafish model to evaluate GLY's in vivo vascular effects, including dyslipidemia and macrophage recruitment.

Main Results:

• GLY induced cellular senescence in HAVSMCs, characterized by altered morphology and increased senescence markers.
• GLY exposure led to oxidative stress, DNA damage, and mitochondrial dysfunction in HAVSMCs.
• In vivo, GLY exposure in zebrafish resulted in dyslipidemia and increased macrophage infiltration in vasculature.

Conclusions:

• Glyphosate induces vascular toxicity through cellular senescence and oxidative stress pathways.
• GLY exposure is associated with dyslipidemia and vascular inflammation, suggesting a potential risk factor for atherosclerosis.
• Findings underscore the need for caution regarding cardiovascular risks in individuals with chronic occupational exposure to glyphosate.