Heart Failure Induces Significant Changes in Nuclear Pore Complex of Human CardiomyocytesReport as inadecuate




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Aims

The objectives of this study were to analyse the effect of heart failure HF on several proteins of nuclear pore complex NPC and their relationship with the human ventricular function.

Methods and Results

A total of 88 human heart samples from ischemic ICM, n = 52 and dilated DCM, n = 36 patients undergoing heart transplant and control donors CNT, n = 9 were analyzed by Western blot. Subcellular distribution of nucleoporins was analysed by fluorescence and immunocytochemistry. When we compared protein levels according to etiology, ICM showed significant higher levels of NDC1 65%, p<0.0001, Nup160 88%, p<0.0001 and Nup153 137%, p = 0.004 than those of the CNT levels. Furthermore, DCM group showed significant differences for NDC1 41%, p<0.0001, Nup160 65%, p<0.0001, Nup153 155%, p = 0.006 and Nup93 88%, p<0.0001 compared with CNT. However, Nup155 and translocated promoter region TPR did not show significant differences in their levels in any etiology. Regarding the distribution of these proteins in cell nucleus, only NDC1 showed differences in HF. In addition, in the pathological group we obtained good relationship between the ventricular function parameters LVEDD and LVESD and Nup160 r = −0382, p = 0.004; r = −0.290, p = 0.033; respectively.

Conclusions

This study shows alterations in specific proteins NDC1, Nup160, Nup153 and Nup93 that compose NPC in ischaemic and dilated human heart. These changes, related to ventricular function, could be accompanied by alterations in the nucleocytoplasmic transport. Therefore, our findings may be the basis for a new approach to HF management.



Author: Estefanía Tarazón, Miguel Rivera, Esther Roselló-Lletí, Maria Micaela Molina-Navarro, Ignacio José Sánchez-Lázaro, Francis

Source: http://plos.srce.hr/



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