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01 July 2006

Lymphotoxin-alpha and cardiovascular disease: Clinical association and pathogenic mechanisms.

Joseph J. Naoum, Hong Chai, Peter H. Lin, Alan B. Lumsden, Qizhi Yao, Changyi Chen

Med Sci Monit 2006; 12(7): RA121-124 :: ID: 452214

Abstract

Inflammation plays an important role in atherosclerotic plaque formation,rupture and thrombogenicity. Many cytokines are the most important biomediates of inflammation and itsassociated vascular lesions. Lymphotoxin-alpha (LTalpha) is part of the tumor necrosis factor (TNF) familyof 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 geneticand clinical studies implicate LTalpha, and its binding and regulatory partner galectin-2, as a riskfactor 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-reactiveprotein, an inflammatory marker. In knockout mice, loss of LTalpha leads to a reduction of atheroscleroticlesion size. Together, these findings support the cytokine LTalpha as a mediator of inflammation andits association with the pathogenesis of cardiovascular disease. However, the molecular mechanisms ofLTalpha -induced cellular responses are largely unknown. Preliminary studies indicate that the combinationof LTalpha subunits, specific interaction with its potential receptors and other cytokines, and signaltransduction 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 warrantedto further understand the role of LTalpha in cardiovascular disease.

Keywords: Cell Differentiation - physiology, Cell Death - physiology, Cardiovascular Diseases - physiopathology, Lymphotoxin-alpha - physiology, Signal Transduction

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750