Caracterizacion de los efectos de la cardiotrofina 1 en cardiomiocitos de rata adulta. Posible implicacion en la cardiopatia hipertensiva de la rata espontaneamente hipertensa

Resumen

Cardiotrophin-1 (CT-1) is a cytokine that exerts hypertrophic and survival actions in neonatal cardiomyocytes interacting witn the heterodimer gpl30/leukaemia inhibitory factor receptor (LIFR). Along with the development of hypertensive heart disease (HHD), cardiomyocyte hypertrophy determines left of heart failure (HF). In the present study we first characterized biological effects of CT-1 on adult cardiomyocytes and we further investigated the pathological role of CT-1 in the development of experimental HHD by means of two experimental approaches: the analysis of CT-1 hypertrophic and survival effects in cardiomyocytes isolated from spontaneously hypertensive rats (SHR), and the study of myocardial CT-1 pathway in association with cardiac remodelling. 30-weeks-old SHR (SHR-30) exhibited a concèntric pattern of LVH and increased CT-1 myocardial expression showed by Western blotting and real time pcr. in cardiomyocytes isolated from SHR-30, CT-1 produced cell widening measured by an image analysis system. SHR-72 with HF exhibited chamber dilatation and augmented cardiomyocyte death demonstrated by TÚNEL staining, caspase-3 activation and parp fragmentation. Compared with SHR-30, SHR-72 presented increased myocardial CT-1 expression, similar amount of gpl30 and diminished LIFR expression analyzed by Western blotting and real time pcr. cardiomyocytes isolated from SHR-72 were completely resistant to hypertrophic and survival effects of CT-1. Present findings suggest a double role for CT-1 pathway in the development of experimental HHD. The cytokine may induce cardiomyocyte hypertrophy in the early phase of LVH and a deficient expression of LIFR may facilitate cell death and the onset of HF.