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J Nutr Biochem. 2010 Jul;21(7):580-8. doi: 10.1016/j.jnutbio.2009.03.003. Epub 2009 May 15.

L-Carnitine attenuates angiotensin II-induced proliferation of cardiac fibroblasts: role of NADPH oxidase inhibition and decreased sphingosine-1-phosphate generation.

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1
Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, ROC.

Abstract

The heart is unable to synthesize L-carnitine and is strictly dependent on the L-carnitine provided by the blood stream; however, additional studies are needed to better understand the mechanism of L-carnitine supplementation to the heart. The aim of this study was to evaluate the effects of L-carnitine on angiotensin II (Ang II)-induced cardiac fibroblast proliferation and to explore its intracellular mechanism(s). Cultured rat cardiac fibroblasts were pretreated with L-carnitine (1-30 mM) then stimulated with Ang II (100 nM). Ang II increased fibroblast proliferation and endothelin-1 expression, which were partially inhibited by L-carnitine. L-carnitine also attenuated Ang II-induced NADPH oxidase activity, reactive oxygen species formation, extracellular signal-regulated kinase phosphorylation, activator protein-1-mediated reporter activity and sphingosine-1-phosphate generation. In addition, L-carnitine increased prostacyclin (PGI(2)) generation in cardiac fibroblasts. siRNA transfection of PGI(2) synthase significantly reduced L-carnitine-induced PGI(2) and its anti-proliferation effects on cardiac fibroblasts. Furthermore, blockading potential PGI(2) receptors, including immunoprecipitation (IP) receptors and peroxisome proliferator-activated receptors alpha (PPAR alpha) and delta, revealed that siRNA-mediated blockage of PPAR alpha considerably reduced the anti-proliferation effect of L-carnitine. In summary, these results suggest that L-carnitine attenuates Ang II-induced effects (including NADPH oxidase activation, sphingosine-1-phosphate generation and cell proliferation) in part through PGI(2) and PPAR alpha-signaling pathways.

PMID:
19447019
DOI:
10.1016/j.jnutbio.2009.03.003
[Indexed for MEDLINE]

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