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.
ASJC Scopus subject areas
- Clinical Biochemistry
- Molecular Biology
- Endocrinology, Diabetes and Metabolism
- Nutrition and Dietetics
Chao, H. H., Chen, C. H., Liu, J. C., Lin, J. W., Wong, K. L., & Cheng, T-H. (2010). L-Carnitine attenuates angiotensin II-induced proliferation of cardiac fibroblasts: Role of NADPH oxidase inhibition and decreased sphingosine-1-phosphate generation. Journal of Nutritional Biochemistry, 21(7), 580-588. https://doi.org/10.1016/j.jnutbio.2009.03.003