I004 Cardiotrophin-1 actions in vascular smooth muscle cells. A role in arterial stiffness

• Published in: Archives of cardiovascular diseases 2009, Vol.102, p.S87-S87
• Main Authors: Lopez, N, Fortuno, M.-A, Labat, C, Sloboda, N, Nuee-Capiaumont, J, Diez, J, Lacolley, P, Zannad, F, Rossignol, P
• Format: Article
• Language: English
• Subjects: Cardiovascular; Internal Medicine
• ISSN: 1875-2136; 1875-2128
• DOI: 10.1016/S1875-2136(09)72338-1

Background & aims Cardiotrophin-1 (CT-1) is a cytokine belonging to the interleukin-6 superfamily that exhibits trophic and survival properties in a number of cell types. CT-1 protein expression has recently been identified within the media of atherosclerotic arteries, but its role in the vessel is still unknown. The present study was designed to investigate the effects of CT-1 in vascular smooth muscle cells (VSMC) and its involvement in the arterial phenotype of CT-1-null mice. Methods Rat aorta primary cultured VSMC were stimulated with CT-1 (10-11-10-9M) and/or antibodies against CT-1 receptors (LIFR or gp130), and/or chemical inhibitors against CT-1-activated intracellular pathways, for up to 48 hours. Cell proliferation was determined by MTT assay and ki67 immunodetection. The expression of collagen type I and III, elastin and fibronectin was quantified by RT-PCR and Western blot. Matrix metalloproteinases (MMPs) activities were assessed by gelatin and casein zymographies. Arterial mechanical properties were evaluated in 2 years-old WT (n=8) and CT-1-null mice (n=3) by echo-tracking device. Circumferential wall stress, incremental elastic modulus (Einc), media cross-sectional area and collagen and elastin content were recorded. Results CT-1 induced VSMC proliferation in a dose-dependent manner (p