Abstract 8573: L-carnitine Prevents Heart Failure with Preserved Ejection Fraction in Associated with Attenuation of Cardiac Fibrosis
Backgrounds: Prognosis of heart failure with preserved ejection fraction (HFpEF) has not been improved because of unknown pathophysiology and unestablished therapeutic strategy. Cardiac fibrosis is known to play a crucial role in the development of HFpEF.
Methods and Results: The comprehensive and quantitative analysis of metabolites with capillary electrophoresis time-of-flight mass spectrometry was conducted to find a substance which may be related to the development of HFpEF, and revealed decreased plasma free-carnitine levels in Dahl salt-sensitive rats (DSR) fed high-salt diet, a model of hypertensive HFpEF. We confirmed this result with enzymatic cycling method by showing decreased plasma and left ventricular (LV) free-carnitine levels with increased urinary free-carnitine excretion in HFpEF rats compared to control DSR fed normal chow. We also found that blood free-carnitine levels were decreased in HFpEF patients compared to age-matched normal volunteers. Expression of organic cation/carnitine transporter 2, which transports free-carnitine into cells, was decreased in the LV and kidney of HFpEF rats. L-carnitine administration to HFpEF rats increased plasma and LV levels of free-carnitine, and prevented HFpEF with decreased myocardial stiffness constant and decreased area of LV fibrosis. In cultured cardiac fibroblasts, L-carnitine attenuated the angiotensin II-induced increase in 3H-proline incorporation. L-carnitine increased prostacyclin production and expression of fatty acid desaturase 1/2, rate-limiting enzymes in forming arachidonic acid, in the LV of DSR and cultured cardiac fibroblasts. LV arachidonic acid levels were increased in HFpEF rats by L-carnitine administration.
Conclusions: L-carnitine may be effective in the prevention of HFpEF through enhanced production of prostacyclin and prevention of LV fibrosis and stiffening. L-carnitine supplementation may become a therapeutic option for HFpEF.
- © 2011 by American Heart Association, Inc.