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

O

Y

X

(CH2)14CH3

O

O

PO3-

Z

O

O

( )n

Oxygen Radicals,Metals

X = -H, -OHY = - O, -OHZ = choline, inosital, -H, etc

LOX-1

CD36 TLR2/4

ImmuneCells

Smooth muscle cellsEndothelial Cells

OY

X

Phospholipid

Oxidized Phospholipid

1. Increased inflammation2. Cellular differentiation3. Calcification

“Immunomodulatory”Receptors

LDL Particle

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.

oxLDL vs Age

Age

oxLD

L (U

/L)

0 20 40 60 80 1000

50

100

150

log (Lox1) vs Age

Age lo

g (L

ox1

pg/m

l)

0 20 40 60 80 1000

1

2

3

4

p= 0.03*

Trends between oxLDL, LOX-1 and age

Preliminary Regression Model Results for Predictors of oxLDL

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.

DiNEH Acknowledgements

• 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

Acknowledgments

Lily