IN VIVO EFFECTS OF CARDIOTROPHIN-1 |
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| Authors: | Hongkui Jin Renhui Yang Gilbert A Keller Anne Ryan Annie Ko David Finkle Todd A Swanson WeiLi Diane Pennica William I Wood Nicholas F Paoni |
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| Institution: | aDepartments of Cardiovascular Research, South San Francisco, CA, U.S.A.;bDepartment of Pharmacokinetics and Metabolism, South San Francisco, CA, U.S.A.;cDepartment of Pathology, South San Francisco, CA, U.S.A.;dDepartment of Molecular Biology Genetech, Inc. South San Francisco, CA, U.S.A. |
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| Abstract: | Cardiotrophin-1 (CT-1) is a recently discovered cytokine that was isolated based on its ability to induce cardiac myocyte hypertrophy in vitro. In this study, the effects of chronic administration of CT-1 to mice (0.5 or 2 μg by intraperitoneal injection, twice a day for 14 days) were determined. A dose-dependent increase in both the heart weight and ventricular weight to body ratios was observed in the treated groups. The body weights of the animals were unaffected. These results indicate that CT-1 can induce cardiac hypertrophy in vivo. CT-1 was not specific for the heart, however. It stimulated the growth of the liver, kidney, and spleen, and caused atrophy of the thymus. CT-1 administration also increased the platelet counts by 70%, with no change in mean platelet volume. Red blood cell counts were increased in the treated animals, and there was a concomitant increase in haemoglobin concentration. Thus, CT-1 has a broad spectrum of biological activities in vivo. This observation is consistent with previous in-vitro findings showing that the mRNA for CT-1 is expressed in several tissues, and that CT-1 can function through binding to the leukaemia inhibitory factor (LIF) receptor and signalling through the gp130 pathway. |
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| Keywords: | cardiac hypertrophy cardiotrophin-1 cytokine haematopoiesis mitochondria |
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