Drinking Water Arsenic Levels Predict Plasma Levels of Oxidized LDL Cholesterol (oxLDL) in Navajo Populations Exposed to Uranium-Contaminated Mining Sites Matthew Campen, Molly Harmon, and Johnnye Lewis
Oxidized LDL and LOX-1 Oxygen Radicals, Metals X = -H, -OH Y = - O, -OH Z = choline, inosital, -H, etc Z Phospholipid PO3- O X (CH2)14CH3 O O ( )n O Oxidized Phospholipid O Y X LDL Particle O Y “Immunomodulatory” Receptors CD36 LOX-1 TLR2/4 Increased inflammation Cellular differentiation Calcification Immune Cells Smooth muscle cells Endothelial Cells
Circulating oxLDL is a marker of cardiovascular disease Holvoet et al. (1998)
Oxidized LDL may promote atherosclerosis • oxLDL activates vascular endothelial cells • oxLDL is proinflammatory • oxLDL stimulates differentiation/migration of vascular smooth muscle • Blockade of oxLDL receptors can reduce atherosclerosis
Methods • Examined traditional (IL-6, CRP) and novel (oxLDL and its receptor LOX-1) plasma biomarkers in a large community of the Navajo Nation • Samples and data were obtained through a culturally appropriate community-based participatory approach • Samples analyzed with enzyme-linked immunoassay (EIA) kits • Biomarker and self-report data were then linked to geospatial data on contamination sites.
Trends between oxLDL, LOX-1 and age p= 0.03*
Interim Results and Conclusions • Proximity to abandoned uranium mines was not a significant predictor of oxLDL or LOX-1. • Estimated annual intake of arsenic was a significant predictor of ox-LDL, and therefore of ox-LDL itself • Age, occupational mining exposure, and the distance of home from the legacy waste exposure are also significant predictors. • These results indicate that arsenic intake may increase markers of cardiovascular risk.
NIEHS, EPA and UNM for financial support Community Advisory Board Ed Carlisle, Jay DeGroat, Herbert Enrico, Thomas Manning,Sr., Lynnea Smith, Jean Whitehorse, UNM-HSC Community Environmental Health Program & Clinical and Translational Science Center Johnnye L. Lewis, PhD; Miranda Cajero, BCH; Matthew Campen, PhD; Jeremy DeGroat; Mallery Downs, RN; Eszter Erdei, PhD; Molly Harmon; Gabriel Huerta, PhD; Curtis Miller; Bernadette Pacheco; Glenn Stark; Mary Woodruff; research nursing support Crownpoint Service Unit, I H S Virgil Davis Navajo Area IHS Lisa Allee, CNM; John Hubbard; Ryan Johnson, MD; Doug Peter, MD UT-Houston Nephrology Donald Molony, MD Southwest Research Information Center Chris Shuey, MPH, Sarah Henio-Adeky, Teddy Nez, Sandy Ramone Students Jamie deLemos, PhD – Tufts Univ. Christine George – Stanford Univ. Tommy Rock, MA, UNM Health Policy Student Christine Samuel-Nakamura, PhD Candidate, UCLA Dartmouth Ben Bostick, PhD University of Arizona Cancer Center & Northern Arizona University, NACRP Jani Ingram, PhD, Margaret Briehl, PhD USEPA Region IX Harry Allen, Rich Bauer, Clancy Tenley State of New Mexico Diagnostic Laboratory Navajo Nation EPA Air Quality Division, Public Water Supply Supervision Program, Superfund Program Navajo Nation Division of Health Former Contributors: Bess Seschillie, Bernice Norton, Jerry Elwood, Harrison Gorman, Harris Arthur (in memoriam), Alta McCabe, Margaret Menache, PhD, Alexis Kaminsky, PhD; Eastern Navajo Health Board Thanks to the many others who’ve contributed DiNEH Acknowledgements