Ex vivo paracrine properties of cardiac tissue: Effects of chronic heart failure.

Autor:	Boucek RJ Jr; Department of Pediatrics, University of Washington/Seattle Children's Research Institute, Seattle, Washington. Electronic address: boucekr@yahoo.com., Steele J; School of Medicine, University of Central Florida, Orlando, Florida., Jacobs JP; Johns Hopkins All Children's Heart Institute, St. Petersburg, Florida., Steele P; Department of Pathology, Johns Hopkins All Children's Hospital, St. Petersburg, Florida., Asante-Korang A; Johns Hopkins All Children's Heart Institute, St. Petersburg, Florida., Quintessenza J; Johns Hopkins All Children's Heart Institute, St. Petersburg, Florida., Steele A; Congenital Heart Institute of Florida, St. Petersburg, Florida.
Jazyk:	angličtina
Zdroj:	The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation [J Heart Lung Transplant] 2015 Jun; Vol. 34 (6), pp. 839-48. Date of Electronic Publication: 2014 Jul 17.
DOI:	10.1016/j.healun.2014.07.010
Abstrakt:	Background: Cardiac regenerative responses are responsive to paracrine factors. We hypothesize that chronic heart failure (HF) in pediatric patients affects cardiac paracrine signaling relevant to resident c-kit(+)cluster of differentiation (CD)34- cardiac stem cells (CSCs). Methods: Discarded atrial septum (huAS) and atrial appendages (huAA) from pediatric patients with HF (huAA-HF; n = 10) or without HF (n = 3) were explanted and suspension explant cultured in media. Conditioned media were screened for 120 human factors using unedited monoclonal antibody-based arrays. Significantly expressed (relative chemiluminescence >30 of 100) factors are reported (secretome). Emigrated cells were immunoselected for c-kit and enumerated as CSCs. Results: After culture Day 7, CSCs emigrate from huAA but not huAS. The huAA secretome during CSC emigration included hepatocyte growth factor (HGF), epithelial cell-derived neutrophil attractant-78 (ENA-78)/chemokine (C-X-C motif) ligand (CXCL) 5, growth-regulated oncogene-α (GRO-α)/CXCL1, and macrophage migration inhibitory factor (MIF), candidate pro-migratory factors not present in the huAS secretome. Survival/proliferation of emigrated CSCs required coculture with cardiac tissue or tissue-conditioned media. Removal of huAA (Day 14) resulted in the loss of all emigrated CSCs (Day 28) and in decreased expression of 13 factors, including HGF, ENA-78/CXCL5, urokinase-type plasminogen activator receptor (uPAR)/CD87, and neutrophil-activating protein-2 (NAP-2)/CXCL7 candidate pro-survival factors. Secretomes of atrial appendages from HF patients have lower expression of 14 factors, including HGF, ENA-78/CXCL5, GRO-α/CXCL1, MIF, NAP-2/CXCL7, uPAR/CD87, and macrophage inflammatory protein-1α compared with AA from patients without HF. Conclusions: Suspension explant culturing models paracrine and innate CSC interactions in the heart. In pediatric patients, heart failure has an enduring effect on the ex vivo cardiac-derived secretome, with lower expression of candidate pro-migratory and pro-survival factors for CSCs. (Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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