TY  - JOUR
A1  - Vecellio, Matteo
A1  - Spallotta, Francesco
A1  - Nanni, Simona
A1  - Colussi, Claudia
A1  - Cencioni, Chiara
A1  - Derlet, Anja
A1  - Bassetti, Beatrice
A1  - Tilenni, Manuela
A1  - Carena, Maria Cristina
A1  - Farsetti, Antonella
A1  - Sbardella, Gianluca
A1  - Castellano, Sabrina
A1  - Mai, Antonello
A1  - Martelli, Fabio
A1  - Pompilio, Giulio
A1  - Capogrossi, Maurizio C.
A1  - Rossini, Alessandra
A1  - Dimmeler, Stefanie
A1  - Zeiher, Andreas M.
A1  - Gaetano, Carlo
T1  - The histone acetylase activator pentadecylidenemalonate 1b rescues proliferation and differentiation in the human cardiac mesenchymal cells of type 2 diabetic patients
T2  - Diabetes
N2  - This study investigates the diabetes-associated alterations present in cardiac mesenchymal cells (CMSC) obtained from normoglycemic (ND-CMSC) and type 2 diabetic patients (D-CMSC), identifying the histone acetylase (HAT) activator pentadecylidenemalonate 1b (SPV106) as a potential pharmacological intervention to restore cellular function. D-CMSC were characterized by a reduced proliferation rate, diminished phosphorylation at histone H3 serine 10 (H3S10P), decreased differentiation potential, and premature cellular senescence. A global histone code profiling of D-CMSC revealed that acetylation on histone H3 lysine 9 (H3K9Ac) and lysine 14 (H3K14Ac) was decreased, whereas the trimethylation of H3K9Ac and lysine 27 significantly increased. These observations were paralleled by a downregulation of the GCN5-related N-acetyltransferases (GNAT) p300/CBP-associated factor and its isoform 5-α general control of amino acid synthesis (GCN5a), determining a relative decrease in total HAT activity. DNA CpG island hypermethylation was detected at promoters of genes involved in cell growth control and genomic stability. Remarkably, treatment with the GNAT proactivator SPV106 restored normal levels of H3K9Ac and H3K14Ac, reduced DNA CpG hypermethylation, and recovered D-CMSC proliferation and differentiation. These results suggest that epigenetic interventions may reverse alterations in human CMSC obtained from diabetic patients.
Y1  - 2014
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/33624
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-336246
SN  - 1939-327X
SN  - 0012-1797
N1  - © 2014 by the American Diabetes Association. See http://creativecommons.org /licenses/by-nc-nd/3.0/ for details.
VL  - 63
IS  - 6
SP  - 2132
EP  - 2147
PB  - American Diabetes Association
CY  - Alexandria, Va
ER  -