User login
A microRNA called MIR-25 is a key mediator of poor cardiac contractility in heart failure, according to a report published online March 12 in Nature.
The findings "suggest that inhibition of MIR-25 may be a novel therapeutic strategy for the treatment of heart failure," wrote Dr. Mark Mercola at Sanford-Burnham Medical Research Institute and the University of California, San Diego, and his associates (Nature 2014 March 12 [doi:10.1038/nature13073]).
The researchers developed a robotic high-throughput screening tool that they used to test 875 human microRNAs. They found that the microRNA MIR-25 markedly delayed calcium update kinetics in cardiomyocytes in vitro and was unregulated in myocardial samples from both mice and humans with severe heart failure.
Researchers also observed a significant decrease in left ventricular contractile function in mice when they used adeno-associated virus 9 (AAV9) to increase MIR-25 levels by about 50%.
Furthermore, the progression of heart failure in mice halted when the investigators injected them with an antisense oligonucleotide (antagomiR) against MIR-25. Furthermore, both cardiac function and survival improved significantly compared with mice injected with a control antagomiR.
The microRNA MIR-25 suppresses messenger RNA encoding a calcium-transporting ATPase called SERCA2a, which is the main mechanism for calcium uptake by cardiomyocytes during excitation-contraction coupling, the researchers said. Decreased SERCA2a activity is a major cause of poor contractility and cardiomyopathy, they noted.
The findings "identified MIR-25 as a critical repressor of SERCA2a and cardiac function during heart failure," the investigators said, adding that delayed calcium uptake kinetics in advanced heart failure are also mediated by changes in potassium channel density, sodium-calcium exchanger expression, and myofilament sensitivity to calcium.
The study was supported by the California Institute for Regenerative Medicine, the National Institutes of Health, Fondation Leducq, and the Sanford-Burnham Medical Research Institute. The authors declared no conflicts of interest.
A microRNA called MIR-25 is a key mediator of poor cardiac contractility in heart failure, according to a report published online March 12 in Nature.
The findings "suggest that inhibition of MIR-25 may be a novel therapeutic strategy for the treatment of heart failure," wrote Dr. Mark Mercola at Sanford-Burnham Medical Research Institute and the University of California, San Diego, and his associates (Nature 2014 March 12 [doi:10.1038/nature13073]).
The researchers developed a robotic high-throughput screening tool that they used to test 875 human microRNAs. They found that the microRNA MIR-25 markedly delayed calcium update kinetics in cardiomyocytes in vitro and was unregulated in myocardial samples from both mice and humans with severe heart failure.
Researchers also observed a significant decrease in left ventricular contractile function in mice when they used adeno-associated virus 9 (AAV9) to increase MIR-25 levels by about 50%.
Furthermore, the progression of heart failure in mice halted when the investigators injected them with an antisense oligonucleotide (antagomiR) against MIR-25. Furthermore, both cardiac function and survival improved significantly compared with mice injected with a control antagomiR.
The microRNA MIR-25 suppresses messenger RNA encoding a calcium-transporting ATPase called SERCA2a, which is the main mechanism for calcium uptake by cardiomyocytes during excitation-contraction coupling, the researchers said. Decreased SERCA2a activity is a major cause of poor contractility and cardiomyopathy, they noted.
The findings "identified MIR-25 as a critical repressor of SERCA2a and cardiac function during heart failure," the investigators said, adding that delayed calcium uptake kinetics in advanced heart failure are also mediated by changes in potassium channel density, sodium-calcium exchanger expression, and myofilament sensitivity to calcium.
The study was supported by the California Institute for Regenerative Medicine, the National Institutes of Health, Fondation Leducq, and the Sanford-Burnham Medical Research Institute. The authors declared no conflicts of interest.
A microRNA called MIR-25 is a key mediator of poor cardiac contractility in heart failure, according to a report published online March 12 in Nature.
The findings "suggest that inhibition of MIR-25 may be a novel therapeutic strategy for the treatment of heart failure," wrote Dr. Mark Mercola at Sanford-Burnham Medical Research Institute and the University of California, San Diego, and his associates (Nature 2014 March 12 [doi:10.1038/nature13073]).
The researchers developed a robotic high-throughput screening tool that they used to test 875 human microRNAs. They found that the microRNA MIR-25 markedly delayed calcium update kinetics in cardiomyocytes in vitro and was unregulated in myocardial samples from both mice and humans with severe heart failure.
Researchers also observed a significant decrease in left ventricular contractile function in mice when they used adeno-associated virus 9 (AAV9) to increase MIR-25 levels by about 50%.
Furthermore, the progression of heart failure in mice halted when the investigators injected them with an antisense oligonucleotide (antagomiR) against MIR-25. Furthermore, both cardiac function and survival improved significantly compared with mice injected with a control antagomiR.
The microRNA MIR-25 suppresses messenger RNA encoding a calcium-transporting ATPase called SERCA2a, which is the main mechanism for calcium uptake by cardiomyocytes during excitation-contraction coupling, the researchers said. Decreased SERCA2a activity is a major cause of poor contractility and cardiomyopathy, they noted.
The findings "identified MIR-25 as a critical repressor of SERCA2a and cardiac function during heart failure," the investigators said, adding that delayed calcium uptake kinetics in advanced heart failure are also mediated by changes in potassium channel density, sodium-calcium exchanger expression, and myofilament sensitivity to calcium.
The study was supported by the California Institute for Regenerative Medicine, the National Institutes of Health, Fondation Leducq, and the Sanford-Burnham Medical Research Institute. The authors declared no conflicts of interest.
FROM NATURE
Major finding: The microRNA MIR-25 markedly delayed calcium update by cardiomyocytes in vitro and was unregulated in mice and humans with heart failure. Overexpression of MIR-25 was associated with decreased heart muscle contractility, while inhibiting MIR-25 stopped the progression of heart failure in mice.
Data source: High-throughput functional screening of the human microRNAome.
Disclosures: The California Institute for Regenerative Medicine, the National Institutes of Health, Fondation Leducq, and the Sanford-Burnham Medical Research Institute supported the research. The authors declared no conflicts of interest.