Speaker Credentials
P3
Speaker Credentials
PharmD
College
College of Pharmacy
Medical Specialty
Cardiology
Format
Poster
Start Date
November 2024
End Date
November 2024
Track
4
Abstract
Objective: To investigate the effect of ketosis on long noncoding RNAs (lncRNAs), specifically MALAT1, and their role in mitochondrial function in AC16 human ventricular cardiomyocytes. Background: Heart failure, a leading cause of death, is increasingly recognized as a metabolic disorder linked to mitochondrial dysfunction. Ketone body treatments have shown potential in improving mitochondrial function and heart failure outcomes. Long noncoding RNAs (lncRNAs), which are RNA molecules longer than 200 nucleotides that do not encode proteins, regulate gene expression and mitochondrial function. Although lncRNAs are modulated during heart failure progression, their specific roles under ketotic conditions remain unclear. Methods: AC16 cardiomyocytes were treated with β-hydroxybutyrate (0.5 mM, 1 mM, 5 mM) for 24, 48, and 72 hours to induce ketosis. Gene expression of MALAT1, ketone oxidation enzymes (MCT1, BDH1, SCOT), mitochondrial biogenesis markers (PGC1α, TFAM), and antioxidant genes (NRF2, SOD1, SOD2) was measured using qPCR. LncRRIsearch was used to predict MALAT1 interactions with mitochondrial-related mRNAs. Results: Ketosis significantly upregulated MALAT1, ketone oxidation genes, mitochondrial biogenesis markers, and antioxidant genes, especially at 72 hours. Computational analysis identified strong interactions between MALAT1 and the mRNAs of NRF2 and PGC1α. Conclusion: This study highlights MALAT1's role in modulating mitochondrial function during ketosis, suggesting its potential as a target for future heart failure therapies involving lncRNAs. Grants: This study was partially funded by a grant from the American Heart Association, and Barry and Judy Silverman College of Pharmacy
Included in
The Role of Long Noncoding RNA MALAT1 in Ketosis-Induced Mitochondrial Modulation in Human Cardiomyocytes
Objective: To investigate the effect of ketosis on long noncoding RNAs (lncRNAs), specifically MALAT1, and their role in mitochondrial function in AC16 human ventricular cardiomyocytes. Background: Heart failure, a leading cause of death, is increasingly recognized as a metabolic disorder linked to mitochondrial dysfunction. Ketone body treatments have shown potential in improving mitochondrial function and heart failure outcomes. Long noncoding RNAs (lncRNAs), which are RNA molecules longer than 200 nucleotides that do not encode proteins, regulate gene expression and mitochondrial function. Although lncRNAs are modulated during heart failure progression, their specific roles under ketotic conditions remain unclear. Methods: AC16 cardiomyocytes were treated with β-hydroxybutyrate (0.5 mM, 1 mM, 5 mM) for 24, 48, and 72 hours to induce ketosis. Gene expression of MALAT1, ketone oxidation enzymes (MCT1, BDH1, SCOT), mitochondrial biogenesis markers (PGC1α, TFAM), and antioxidant genes (NRF2, SOD1, SOD2) was measured using qPCR. LncRRIsearch was used to predict MALAT1 interactions with mitochondrial-related mRNAs. Results: Ketosis significantly upregulated MALAT1, ketone oxidation genes, mitochondrial biogenesis markers, and antioxidant genes, especially at 72 hours. Computational analysis identified strong interactions between MALAT1 and the mRNAs of NRF2 and PGC1α. Conclusion: This study highlights MALAT1's role in modulating mitochondrial function during ketosis, suggesting its potential as a target for future heart failure therapies involving lncRNAs. Grants: This study was partially funded by a grant from the American Heart Association, and Barry and Judy Silverman College of Pharmacy