Circulating lymphotoxin β receptor and atherosclerosis: observations from the Dallas Heart Study.
OBJECTIVE
Lymphotoxin β receptor (LTβR), a member of the tumor necrosis factor superfamily, binds ligands expressed by activated lymphocytes. Interruption of LTβR signaling improves autoimmune diseases and alters lipid homeostasis. We assayed circulating LTβR and examined its association with atherosclerosis phenotypes in a population-based sample.


RESULTS
Plasma LTβR was measured by ELISA in 3215 subjects enrolled in the Dallas Heart Study. Atherosclerosis was assessed using CT measurements of coronary calcium (CAC) and abdominal MRI measurements of aortic plaque (AP) (n=2252) and aortic wall thickness (AWT) (n=2265). We analyzed associations between LTβR and atherosclerosis using multivariable logistic and linear regression methods. Higher levels of LTβR associated with most traditional cardiovascular risk factors, multiple inflammatory markers, and markers of cardiac injury. Univariable analyses demonstrated significant associations of LTβR with CAC, AP, and AWT (p<0.0001 for each). In multivariable models adjusted for traditional risk factors, the 4th vs. the 1st quartile of LTβR remained associated with prevalent CAC, AP, and increased AWT (all p<0.05). Similar associations were observed when LTβR was modeled as a log-transformed continuous variable.


CONCLUSIONS
LTβR levels are independently associated with atherosclerosis in multiple vascular beds. These findings support further investigation of the lymphotoxin/LTβR pathway in atherosclerosis.
Owens
Andrew W
AW
Donald W. Reynolds Cardiovascular Clinical Research Center at the University of Texas Southwestern Medical Center, Dallas, TX 75390-9047, United States.
Matulevicius
Susan
S
Rohatgi
Anand
A
Ayers
Colby R
CR
Das
Sandeep R
SR
Khera
Amit
A
McGuire
Darren K
DK
de Lemos
James A
JA
D000328:Adult; D000368:Aged; D050197:Atherosclerosis / Q000097:blood* / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D053259:Lymphotoxin beta Receptor / Q000097:blood*; D008875:Middle Aged; D015999:Multivariate Analysis; D010641:Phenotype; D012044:Regression Analysis; D012307:Risk Factors; D014057:Tomography, X-Ray Computed / Q000379:methods; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015415:Biomarkers; D053259:Lymphotoxin beta Receptor; D014409:Tumor Necrosis Factor-alpha