Abstract
Tumor necrosis factor-stimulated gene-6 (TSG-6) is a 35-kDa glycoprotein that has been shown to exert anti-inflammatory effects in experimental models of arthritis, acute myocardial infarction, and acute cerebral infarction. Several lines of evidence have shed light on the pathophysiological roles of TSG-6 in atherosclerosis. TSG-6 suppresses inflammatory responses of endothelial cells, neutrophils, and macrophages as well as macrophage foam cell formation and vascular smooth muscle cell (VSMC) migration and proliferation. Exogenous TSG-6 infusion and endogenous TSG-6 attenuation with a neutralizing antibody for four weeks retards and accelerates, respectively, the development of aortic atherosclerotic lesions in ApoE-deficient mice. TSG-6 also decreases the macrophage/VSMC ratio (a marker of plaque instability) and promotes collagen fibers in atheromatous plaques. In patients with coronary artery disease (CAD), plasma TSG-6 levels are increased and TSG-6 is abundantly expressed in the fibrous cap within coronary atheromatous plaques, indicating that TSG-6 increases to counteract the progression of atherosclerosis and stabilize the plaque. These findings indicate that endogenous TSG-6 enhancement and exogenous TSG-6 replacement treatments are expected to emerge as new lines of therapy against atherosclerosis and related CAD. Therefore, this review provides support for the clinical utility of TSG-6 in the diagnosis and treatment of atherosclerotic cardiovascular diseases.
Highlights
Atherosclerotic cardiovascular diseases, such as coronary artery disease (CAD) and stroke, are a leading cause of mortality worldwide [1]
Atherosclerosis is characterized by a complex interaction of vascular endothelial injury, inflammation with monocyte adhesion to endothelial cells (ECs), lipid deposition with macrophage foam cells, and the migration and proliferation of vascular smooth muscle cells (VSMCs) accompanied by extracellular matrix (ECM) remodeling [2]
tumor necrosis factor-stimulated gene-6 (TSG-6), which maps to human chromosome 2q23.3, was originally identified as the sixth gene product induced by tumor necrosis factor-α (TNF-α) in human fibroblasts [11], and is called Tnfaip6 or Tnfip6
Summary
Atherosclerotic cardiovascular diseases, such as coronary artery disease (CAD) and stroke, are a leading cause of mortality worldwide [1]. The prevalence of traditional risk factors for CAD, such as diabetes, hypertension, dyslipidemia, obesity, and others, has been increasing worldwide, with consequent increases in the rates of coronary and cerebrovascular events [1]. We are paying more attention to tumor necrosis factor-stimulated gene-6 (TSG-6) as an anti-atherogenic protein [10]. There has been recent progress in TSG-6 studies. The present article reviews the recent literature and introduces our new data regarding the role of TSG-6 in the pathogenesis of atherosclerosis and as a biomarker and novel potential therapeutic target for atherosclerotic cardiovascular diseases
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