Lymphotoxin-alpha and cardiovascular disease: clinical association and pathogenic mechanisms.
Inflammation plays an important role in atherosclerotic plaque formation, rupture and thrombogenicity. Many cytokines are the most important biomediates of inflammation and its associated vascular lesions. Lymphotoxin-alpha (LTalpha) is part of the tumor necrosis factor (TNF) family of cytokines that mediates an inflammatory or immunologic response that can affect cell death or differentiation, and provide an important link of communication between lymphocytes and stromal cells. Several genetic and clinical studies implicate LTalpha, and its binding and regulatory partner galectin-2, as a risk factor in the pathogenesis of cardiovascular diseases including miocardial infarction, aortic aneurysm, and cerebral infarction. The LTalpha gene variability is also associated with an increased level of C-reactive protein, an inflammatory marker. In knockout mice, loss of LTalpha leads to a reduction of atherosclerotic lesion size. Together, these findings support the cytokine LTalpha as a mediator of inflammation and its association with the pathogenesis of cardiovascular disease. However, the molecular mechanisms of LTalpha -induced cellular responses are largely unknown. Preliminary studies indicate that the combination of LTalpha subunits, specific interaction with its potential receptors and other cytokines, and signal transduction pathways may significantly contribute to the overall effects of LTalpha on the inflammation, gene expression, and functions of cardiovascular cells. More clinical and basic science studies are warranted to further understand the role of LTalpha in cardiovascular disease.
Naoum
Joseph J
JJ
Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, USA.
Chai
Hong
H
Lin
Peter H
PH
Lumsden
Alan B
AB
Yao
Qizhi
Q
Chen
Changyi
C
D002318:Cardiovascular Diseases / Q000473:pathology / Q000503:physiopathology*; D016923:Cell Death / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D006801:Humans; D008233:Lymphotoxin-alpha / Q000502:physiology*; D015398:Signal Transduction
D008233:Lymphotoxin-alpha