Circulating lymphotoxin β receptor and atherosclerosis: Observations from the Dallas Heart Study

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11 Citations (Scopus)

Abstract

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. Methods and 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. Conclusion: LTβR levels are independently associated with atherosclerosis in multiple vascular beds. These findings support further investigation of the lymphotoxin/LTβR pathway in atherosclerosis.

Original languageEnglish (US)
Pages (from-to)601-606
Number of pages6
JournalAtherosclerosis
Volume212
Issue number2
DOIs
StatePublished - Oct 2010

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Lymphotoxin-alpha
Atherosclerosis
Calcium
Tumor Necrosis Factors
Autoimmune Diseases
Blood Vessels
Linear Models
Homeostasis

Keywords

  • Aortic plaque
  • Atherosclerosis
  • Biomarker
  • Coronary calcium
  • LTβR
  • Lymphotoxin

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

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title = "Circulating lymphotoxin β receptor and atherosclerosis: Observations from the Dallas Heart Study",
abstract = "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. Methods and 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. Conclusion: LTβR levels are independently associated with atherosclerosis in multiple vascular beds. These findings support further investigation of the lymphotoxin/LTβR pathway in atherosclerosis.",
keywords = "Aortic plaque, Atherosclerosis, Biomarker, Coronary calcium, LTβR, Lymphotoxin",
author = "Owens, {Andrew W.} and Matulevicius, {Susan A} and Rohatgi, {Anand K} and Ayers, {Colby R.} and Das, {Sandeep R} and Amit Khera and McGuire, {Darren K} and {de Lemos}, {James A}",
year = "2010",
month = "10",
doi = "10.1016/j.atherosclerosis.2010.06.003",
language = "English (US)",
volume = "212",
pages = "601--606",
journal = "Atherosclerosis",
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T1 - Circulating lymphotoxin β receptor and atherosclerosis

T2 - Observations from the Dallas Heart Study

AU - Owens, Andrew W.

AU - Matulevicius, Susan A

AU - Rohatgi, Anand K

AU - Ayers, Colby R.

AU - Das, Sandeep R

AU - Khera, Amit

AU - McGuire, Darren K

AU - de Lemos, James A

PY - 2010/10

Y1 - 2010/10

N2 - 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. Methods and 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. Conclusion: LTβR levels are independently associated with atherosclerosis in multiple vascular beds. These findings support further investigation of the lymphotoxin/LTβR pathway in atherosclerosis.

AB - 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. Methods and 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. Conclusion: LTβR levels are independently associated with atherosclerosis in multiple vascular beds. These findings support further investigation of the lymphotoxin/LTβR pathway in atherosclerosis.

KW - Aortic plaque

KW - Atherosclerosis

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KW - Coronary calcium

KW - LTβR

KW - Lymphotoxin

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