Difluoromethylornithine inhibits hypertrophic, pro-fibrotic and pro-apoptotic actions of aldosterone in cardiac cells.
Recent studies have shown that aldosterone may play a critical role in the transition to heart failure and that heart is a direct target of the action of aldosterone, which can provoke hypertrophy and apoptosis of isolated cardiomyocytes and also increase the expression of genes that favor tissue fibrosis. Early work from this and other laboratories has established a link between the aliphatic polyamines and cardiac hypertrophy, while more recently an involvement of polyamines even in cell death and survival has emerged. In the present study we have treated cardiac cells, i.e. rat H9c2 cardiomyoblasts and neonatal cardiomyocytes, with (D, L)-2-(difluoromethyl)ornithine, a specific inhibitor of polyamine biosynthesis, to investigate the effects of polyamines in relation to the hypertrophic, pro-fibrotic and pro-apoptotic actions of aldosterone. The results indicate that inhibition of polyamine biosynthesis may prevent or attenuate the adverse actions of aldosterone, by modulating the expression of genes related to cardiac hypertrophy and fibrosis, as well as the levels of proteins and the activities of enzymes that control apoptosis.
Cetrullo
S
S
Department of Biochemistry "G. Moruzzi", University of Bologna, Via Irnerio, 48, 40126 Bologna, Italy.
Facchini
A
A
Stanic
I
I
Tantini
B
B
Pignatti
C
C
Caldarera
C M
CM
Flamigni
F
F
D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015317:Biogenic Polyamines / Q000096:biosynthesis; D002478:Cells, Cultured; D000518:Eflornithine / Q000737:chemistry / Q000494:pharmacology*; D005355:Fibrosis / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006331:Heart Diseases / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D006984:Hypertrophy / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
D015317:Biogenic Polyamines; D000450:Aldosterone; D000518:Eflornithine