Ketone bodies in Right Ventricular Failure: A Unique Therapeutic Opportunity.
Madelyn BlakePatrycja PuchalskaFelipe KazmirczakThenappan ThenappanPeter A CrawfordKurt W PrinsPublished in: bioRxiv : the preprint server for biology (2023)
Ketone bodies are pleotropic metabolites that play important roles in multiple biological processes ranging from bioenergetics, to inflammation regulation via suppression of the NLRP3 inflammasome, and epigenetic modifications. Ketone bodies are elevated in left ventricular failure (LVF) and approaches that increase ketone concentrations exert beneficial effects in rodents and humans. However, the regulation of ketones in right ventricular failure (RVF) are unexplored. Here, we show in human pulmonary arterial hypertension (PAH), a compensatory ketosis is absent in patients with RVF. In the monocrotaline rat model of PAH-mediated RVF, a dietary-induced ketosis improves RV function, suppresses NLRP3 inflammasome activation, and combats RV fibrosis. These data suggest ketogenic therapies may particularly effective in RVF, and future studies evaluating the effects of ketones in RVF are warranted.
Keyphrases
- nlrp inflammasome
- pulmonary arterial hypertension
- pulmonary hypertension
- mycobacterium tuberculosis
- pulmonary artery
- left ventricular
- endothelial cells
- oxidative stress
- heart failure
- high glucose
- dna methylation
- signaling pathway
- electronic health record
- ms ms
- polycyclic aromatic hydrocarbons
- hypertrophic cardiomyopathy
- aortic stenosis
- drug induced
- mitral valve
- induced pluripotent stem cells
- aortic valve
- atrial fibrillation
- machine learning
- left atrial
- data analysis