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 (PGI2) generation in cardiac fibroblasts. siRNA transfection of PGI2 synthase significantly reduced l-carnitine-induced PGI2 and its anti-proliferation effects on cardiac fibroblasts. Furthermore, blockading potential PGI2 receptors, including immunoprecipitation (IP) receptors and peroxisome proliferator-activated receptors alpha (PPAR?) and delta , revealed that siRNA-mediated blockage of PPAR? 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 PGI2 and PPAR?-signaling pathways.
Original language | English |
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Pages (from-to) | 580-588 |
Number of pages | 9 |
Journal | Journal of Nutritional Biochemistry |
Volume | 21 |
Issue number | 7 |
DOIs | |
Publication status | Published - Jul 2010 |
Keywords
- Angiotensin II
- Cardiac fibroblasts
- L-carnitine
- NADPH oxidase
- Prostacyclin
- Sphingosine-1-phosphate
ASJC Scopus subject areas
- Biochemistry
- Clinical Biochemistry
- Molecular Biology
- Endocrinology, Diabetes and Metabolism
- Nutrition and Dietetics
- Medicine(all)