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dc.contributor.authorStöhr, Eric J.
dc.date.accessioned2018-10-25T16:09:16Z
dc.date.available2018-10-25T16:09:16Z
dc.date.issued2018-08-24
dc.identifier.citationCastillero, E., Ali, Z.A., Akashi, H., Giangreco, N., Wang, C., Stöhr, E.J., Ji, R., Zhang, X., Kheysin, N., Park, J.E.S. and Hegde, S. (2018) 'Structural and functional cardiac profile after prolonged duration of mechanical unloading: potential implications for myocardial recovery', American Journal of Physiology-Heart and Circulatory Physiology, 315(5), pp.H1463-H1476.
dc.identifier.urihttp://hdl.handle.net/10369/10149
dc.description.abstractClinical and experimental studies have suggested that the duration of left ventricular assist device (LVAD) support may affect remodeling of the failing heart. We aimed to (1) characterize the changes in calcium/calmodulin-dependent protein kinase type II (CaMKII)δ, growth signaling, structural proteins, fibrosis, apoptosis and gene expression before and after LVAD support and (2) assess whether the duration of support correlated with improvement or worsening of reverse remodeling. LV apex tissue and serum pairs were collected in patients with dilated cardiomyopathy (n=25, 23 male) at LVAD implantation and after LVAD support at cardiac transplantation/LVAD explantation. Normal cardiac tissue was obtained from healthy hearts (n=4) and normal serum from aged-matched controls (n=4). The duration of LVAD support ranged from 48 to 1170 days (median duration 270 days). LVAD support was associated with CaMKIIδ activation, increased nuclear myocyte enhancer factor-2 (MEF2), sustained histone deacetylase-4 (HDAC4) phosphorylation, increased circulating and cardiac myostatin (MSTN) and MSTN signaling mediated by SMAD2, ongoing structural protein dysregulation and sustained fibrosis and apoptosis (all p<0.05). Increased CamKIIδ phosphorylation, nuclear MEF2, cardiac MSTN significantly correlated with duration of support. Phosphorylation of SMAD2 and apoptosis decreased with shorter duration of LVAD support but increased with longer duration of LVAD support. Further study is needed to define the optimal duration of LVAD support in patients with dilated cardiomyopathy.en_US
dc.language.isoenen_US
dc.titleStructural and Functional Cardiac Profile after Prolonged Duration of Mechanical Unloading: Potential Implications for Myocardial Recoveryen_US
dc.typeArticleen_US
dc.identifier.doihttps://doi.org/10.1152/ajpheart.00187.2018
rioxxterms.versionAMen_US


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