Molecular Alterations of Nucleocytoplasmic Transport in Patients on the Heart Transplantation Waiting List and Its Correlation With the Severity and Etiology of Heart Failure

• Published in: Transplantation proceedings Vol. 51; no. 2; pp. 369 - 371
• Main Authors: Ezzitouny, M., Sánchez-Lázaro, I., Rivera, M., Portolés-Sanz, M., Roselló-Lletí, E., Gil-Cayuela, C., Almenar-Bonet, L., López-Vilella, R., Ferré-Vallverdú, M., Sanz-Sánchez, J., Cerveró-Rubio, A., Jiménez-Aguilella, J.J., Pérez-Roselló, V., Donoso-Trenado, V., Arenas-Martín, P., Lozano-Edo, S., Jover-Pastor, P., Martínez-Dolz, L.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-03-2019
• Subjects: Active Transport, Cell Nucleus - physiology; Adult; Cardiomyopathy, Dilated - complications; Cardiomyopathy, Dilated - metabolism; Cardiomyopathy, Dilated - physiopathology; Female; Heart Failure - etiology; Heart Failure - metabolism; Heart Failure - physiopathology; Heart Transplantation; Humans; Male; Middle Aged; Myocardial Ischemia - complications; Myocardial Ischemia - metabolism; Myocardial Ischemia - physiopathology; Myocytes, Cardiac - metabolism; Risk Assessment; Waiting Lists
• ISSN: 0041-1345; 1873-2623
• DOI: 10.1016/j.transproceed.2018.12.013

To evaluate whether the levels of some molecules implicated in nucleocytoplasmic transport in human cardiomyocytes are related to the severity of heart failure (HF) in patients on the heart transplantation (HT) waiting list, and to determine whether there is a differential pattern of molecular alteration between ischemic cardiomyopathy (ICM) and non-ischemic dilated cardiomyopathy (DCM).
Sixty-three blood samples collected before HT were analyzed to identify the levels of IMPORTIN5 (IMP5); IMPORTINalpha2; ATPaseCaTransp (ATPCa); NUCLEOPORIN153kDa (Nup153); NUCLEOPORIN160kDa (Nup160); RANGTPaseAP1 (RanGAP1) and EXPORTIN4 (EXP4). These data were then compared between patients with advanced HF with or without the need for ventricular support with extracorporeal membrane oxygenation (ECMO) as a bridge for HT, as well as between patients with non-ischemic DCM and patients with ICM.
Thirty-three patients had ICM, 26 had non-ischemic DCM, and 4 had heart disease. Seventeen patients required ventricular assistance as a bridge to HT. The levels of ATPCa, RanGAP1, and IMP5 were significantly higher in patients with ECMO, while EXP4 was significantly higher in patients without ECMO. Patients with DCM showed higher levels of IMP5, RanGAP1, and Nup153 than those with ICM.
Patients with advanced HF in critical condition (with ECMO as a bridge for HT) presented with significantly higher levels of ATPCa, RanGAP1, and IMP5, while patients with DCM had significantly higher levels of RanGAP1, IMP5, and Nup153. It remains to be clarified whether the determination of these molecules would facilitate the early identification of this group or if their alteration occurs as consequence of circulatory support with ECMO.
•In the myocardiocytes of patients with advanced heart failure, there are alterations in the nuclear-cytoplasmic transport that involve several important molecules (importins, exportins, etc).•Identifying these alterations can help us to better understand the pathophysiology of advanced heart failure and its clinical evolution toward the need for circulatory assistance and later toward heart transplantation.•The presence of different patterns of alterations according to the etiology and severity of advanced heart failure will be a good marker to identify early those patients whose evolution in the short term may be worse, with the need for implantation of a circulatory assistance as a bridge to transplantation.