Emerging Roles of Cardiotrophin-1 in the Pathogenesis and Biomarker of Atherosclerosis

Takuya Watanabe, Hanae Konii and Kengo Sato
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Takuya Watanabe: Laboratory of Cardiovascular Medicine, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan
Hanae Konii: Laboratory of Cardiovascular Medicine, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan
Kengo Sato: Laboratory of Cardiovascular Medicine, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan

J, 2018, vol. 1, issue 1, 1-12

Abstract: Cardiotrophin-1 (CT-1), an interleukin-6 family cytokine, is known as an active inducer capable of cardiac hypertrophy and vascular stiffness in hypertensive heart disease. CT-1 is expressed at high levels in the heart, vascular endothelial cells (ECs), and adipocytes. CT-1 stimulates inflammatory and proatherogenic molecule expression in human monocytes and ECs, as well as monocyte-EC adhesion. CT-1 enhances oxidized low-density lipoprotein-induced foam-cell formation in human monocyte-derived macrophages. CT-1 stimulates the migration, proliferation, and colloagen-1 production in human vascular smooth muscle cells. Chronic CT-1 infusion into Apoe −/− mice accelerates the development of aortic atherosclerotic lesions. CT-1 is expressed at high levels in ECs and macrophage foam cells within atheromatous plaques in Apoe −/− mice. A blockade of CT-1 using anti-CT-1 neutralizing antibody results in the prevention of atherogenesis in Apoe −/− mice. Plasma CT-1 concentrations are elevated in patients with hypertensive heart disease, ischemic heart disease, and metabolic syndrome, and are positively associated with the severity of cardiac hypertrophy, heart failure, and atherosclerosis. Increased plasma concentration of CT-1 is a predictor of death and heart failure following acute myocardial infarction. Therefore, CT-1 serves a novel therapeutic target for atherosclerosis and related diseases. Plasma CT-1 may be a reliable biomarker for atherosclerotic cardiovascular diseases.

Keywords: cardiotrophin-1; atherosclerosis; monocyte; macrophage; vascular smooth muscle cell; endothelial cell; coronary artery disease; hypertension (search for similar items in EconPapers)
JEL-codes: I1 I10 I12 I13 I14 I18 I19 (search for similar items in EconPapers)
Date: 2018
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