Document Detail

L-Carnitine prevents the development of ventricular fibrosis and heart failure with preserved ejection fraction in hypertensive heart disease.
MedLine Citation:
PMID:  22796714     Owner:  NLM     Status:  Publisher    
OBJECTIVES:: Prognosis of heart failure with preserved ejection fraction (HFpEF) remains poor because of unknown pathophysiology and unestablished therapeutic strategy. This study aimed to identify a potential therapeutic intervention for HFpEF through metabolomics-based analysis. METHODS AND RESULTS:: Metabolomics with capillary electrophoresis time-of-flight mass spectrometry was performed using plasma of Dahl salt-sensitive rats fed high-salt diet, a model of hypertensive HFpEF, and showed decreased free-carnitine levels. Reassessment with enzymatic cycling method revealed the decreased plasma and left-ventricular free-carnitine levels in the HFpEF model. Urinary free-carnitine excretion was increased, and the expression of organic cation/carnitine transporter 2, which transports free-carnitine into cells, was down-regulated in the left ventricle (LV) and kidney in the HFpEF model. L-Carnitine was administered to the hypertensive HFpEF model. L-Carnitine treatment restored left-ventricular free-carnitine levels, attenuated left-ventricular fibrosis and stiffening, prevented pulmonary congestion, and improved survival in the HFpEF model independent of the antihypertensive effects, accompanied with increased expression of fatty acid desaturase (FADS) 1/2, rate-limiting enzymes in forming arachidonic acid, and enhanced production of arachidonic acid, a precursor of prostacyclin, and prostacyclin in the LV. In cultured cardiac fibroblasts, L-carnitine attenuated the angiotensin II-induced collagen production with increased FADS1/2 expression and enhanced production of arachidonic acid and prostacyclin. L-Carnitine-induced increase of arachidonic acid was canceled by knock-down of FADS1 or FADS2 in cultured cardiac fibroblasts. Serum free-carnitine levels were decreased in HFpEF patients. CONCLUSIONS:: L-carnitine supplementation attenuates cardiac fibrosis by increasing prostacyclin production through arachidonic acid pathway, and may be a promising therapeutic option for HFpEF.
Yosuke Omori; Tomohito Ohtani; Yasushi Sakata; Toshiaki Mano; Yasuharu Takeda; Shunsuke Tamaki; Yasumasa Tsukamoto; Daisuke Kamimura; Yoshihiro Aizawa; Takeshi Miwa; Issei Komuro; Tomoyoshi Soga; Kazuhiro Yamamoto
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-7-12
Journal Detail:
Title:  Journal of hypertension     Volume:  -     ISSN:  1473-5598     ISO Abbreviation:  -     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-7-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8306882     Medline TA:  J Hypertens     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
aDepartment of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita bGenome Information Research Center, Osaka University, Suita, Osaka cInstitute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata dDepartment of Molecular Medicine and Therapeutics, Faculty of Medicine, Tottori University, Yonago, Tottori, Japan *Yosuke Omori and Tomohito Ohtani contributed equally to the writing of this article.
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