l-Carnitine therapy improves right heart dysfunction through Cpt1-dependent fatty acid oxidation
Vineet Agrawal1, Anna R Hemnes2, Nicholas J Shelburne2
1Department of Medicine, Division of Cardiovascular Medicine Vanderbilt University Medical Center Nashville Tennessee USA.
Pulmonary Circulation
|August 1, 2022
Summary
Pulmonary arterial hypertension causes right ventricular failure due to impaired fatty acid oxidation. L-carnitine supplementation reversed this failure by boosting fatty acid oxidation and reducing lipid buildup in the failing right ventricle.
Area of Science:
- Cardiovascular Research
- Metabolic Disease
- Pulmonary Hypertension
Background:
- Pulmonary arterial hypertension (PAH) leads to fatal right ventricular (RV) failure.
- RV failure involves decreased fatty acid oxidation and lipid accumulation.
- Carnitine deficiency may drive these metabolic changes in the RV.
Purpose of the Study:
- To test if carnitine deficiency drives RV failure in PAH.
- To determine if l-carnitine supplementation can reverse lipotoxic RV failure.
- To investigate the mechanisms of l-carnitine's effects on RV function.
Main Methods:
- In vivo studies using transgenic mice with BMPR2 mutations and pulmonary artery banding models.
- In vitro experiments assessing mitochondrial function and lipid metabolism.
- Measurement of RV cardiac output, ejection fraction, and lipid content.
- Analysis of PPARγ expression and fatty acid oxidation pathways.
Main Results:
- L-carnitine supplementation reversed RV failure in mouse models.
- Improved RV cardiac output and ejection fraction were observed.
- Decreased RV lipid accumulation and augmented fatty acid oxidation were confirmed.
- L-carnitine increased fatty acid oxidation via a Cpt1-dependent pathway in vitro.
Conclusions:
- L-carnitine supplementation improves RV contractility and reduces lipid accumulation in stressed RVs.
- Correcting carnitine deficiency with l-carnitine may reverse RV failure in PAH.
- This highlights a potential therapeutic strategy targeting metabolic dysfunction in PAH-associated RV failure.
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