Arsenic association with circulating oxidized low-density lipoprotein in a Native American community

Area of Science:

• Environmental Health
• Cardiovascular Toxicology
• Native American Health

Background:

• Abandoned uranium mines in the Navajo Nation release uranium, arsenic, and other metals into the environment.
• Potential cardiovascular health effects from cumulative metal exposure are not well understood.
• Oxidation of low-density lipoprotein (LDL) cholesterol is a key factor in vascular inflammation and disease.

Purpose of the Study:

• To investigate if environmental exposure to arsenic and uranium promotes or exacerbates LDL cholesterol oxidation in a Navajo cohort.
• To assess the correlation between cardiovascular biomarkers and metal intake from water and urine.
• To determine if arsenic and uranium can directly oxidize human LDL in laboratory assays.

Main Methods:

• Linear regression analysis of cardiovascular biomarkers (oxidized LDL, C-reactive protein) against estimated mean annual arsenic and uranium intake in a Navajo cohort (n=252).
• Analysis of metals in drinking water and urine samples.
• In vitro assays to assess the direct effects of arsenic and uranium on purified human LDL oxidation and lipid peroxidation.

Main Results:

• Mean annual arsenic intake from water was significantly associated with increased oxidized LDL (oxLDL).
• Uranium intake was negatively associated with oxLDL.
• In vitro, arsenic directly oxidized LDL's apolipoprotein B-100, but neither metal induced lipid peroxidation.

Conclusions:

• Arsenic exposure is consistent with promoting LDL oxidation, a critical step in vascular disease development.
• Uranium exposure did not show a similar association with LDL oxidation and had minimal direct effects on LDL in experiments.
• Findings suggest arsenic, not uranium, may be a significant contributor to vascular inflammation via LDL oxidation in this population.