Abstract 8775: Nucleocytoplasmic Transport and Left Ventricular Function in Heart Failure
Introduction: We have shown previously alterations in nucleocytoplasmic transport (NCT) in patients with heart failure (HF), such as higher levels and different distribution of importins, exportins and Ran regulators in ischemic and dilated human hearts, when compared with controls. Therefore the aim of this study was to calculate if there are any correlations between cargo protein levels (IMP-α2, IMP-β3, EXP-1 and EXP-4) and left ventricular function parameters [left ventricular end-diastole dimension (LVEDD), left ventricular end-systolic dimension (LVESD)], and left ventricular mass index (LVMI).
Hypothesis: We assessed the hypothesis that NCT may be related to left ventricular function.
Methods: We studied 46 Caucasian patients undergoing heart transplant (mean age 50±10 years, 43 males). Thirty were diagnosed with ischemic cardiomyopathy and 16 with dilated cardiomyopathy. A routine physical examination, laboratory analyses, and echo-Doppler study were performed. In the explanted hearts we analyzed by Western blot IMP-α2, IMP-β3, EXP-1 and EXP-4 levels. Furthermore, sub-cellular distribution of proteins was analyzed by fluorescence microscopy.
Results: For the whole population LVEDD was 70 mm, LVESD 62.5 mm and LVMI 178 g/m2. By Western blot analysis IMP- β3 levels were 264 ± 93 au, IMP- α2 163 ± 43 au, EXP-1 293 ± 130 au and EXP-4 169 ± 69 au. When we correlated IMP-β3 levels with LVEDD we found r=0.38, p<0.05. When we correlated IMP-β3 levels with LVESD, we found r=0.4, p<0.05. The correlation of IMP-β3 with LVMI was r=0.57, p<0.01. Moreover, there was a significant relationship between exportins (EXP-1) with LVEDD, r=0.410, p<0.05. The correlation of EXP-1 levels with LVMI was r=0.438, p<0.05.
Conclusions: In this study we found significant relationships between exportin and importin levels, markers of nucleocytoplasmic transport, and left ventricular functional parameters calculated by echo-Doppler imaging. This fact may be closely related with the cardiomyocyte capability of repair and may open new therapeutic expectations in patients with heart failure.
- © 2010 by American Heart Association, Inc.