according to a study by eLife, researchers found a kind of micro peptide molecule that can restore normal heart function of mice. This molecule works by preventing calcium regulation disorders and heart remodeling, and may be a promising new gene therapy target for heart failure.
In many processes leading to heart failure, the destruction caused by calcium is the most prominent. The activity of calcium in and out of cells can make the heart muscle contract and relax. A calcium pump called SERCA controls the flow of calcium, but the role of the molecule is impaired in heart failure. Previous studies have proposed that enhancing the activity of SERCA can maintain the contractility of the heart and treat heart failure.
"Our lab recently found a micropeptide called dworf, which binds directly to SERCA and enhances its activity," explains Catherine makarewich, a postdoctoral researcher at the University of Texas Southwestern Medical Center. "In this study, we explored the therapeutic potential of high-level dworf as a way to increase SERCA activity and improve cardiac contractility in heart failure."
Previous work by the team has shown that dworf works by replacing molecules that inhibit SERCA, known as phosphoprotein (PIN). To further investigate this, they designed mice with higher levels of dworf and / or PLN in the heart and then studied their effects.
They found that engineered mice and normal mice had similar cardiac functions and structures, but mice designed to have a higher level of dworf showed increased calcium circulation. In contrast, cardiomyocytes from mice with higher levels of PLN showed opposite and reduced contractility. In mice designed to have a high level of dworf and PLN, the adverse reactions of excessive PLN were completely prevented, indicating that dworf can protect it from its pathological activity.
To further investigate the problem, the team looked at the effect of elevated dworf levels in mice with dilated cardiomyopathy - a condition in which the heart becomes larger and cannot be aspirated normally. When studied by echocardiography, mice with cardiomyopathy had reduced contractility in the left ventricle of the heart, as indicated by a lower ejection fraction (the amount of blood ejected from the ventricle per contraction). In contrast, the left ventricular function of mice with high level of dworf was significantly improved. The thermal function of dworf free mice decreased even more than that of normal mice with cardiomyopathy.
High level of dworf can also effectively alleviate the disease markers such as the thinning of ventricular wall and the increase of myocardial cell volume. The accumulation of scar tissue in the heart is also a characteristic of myopathy, which can be prevented in mice with elevated dworf levels. In conclusion, the results show that dworf can prevent the functional and structural effects of cardiomyopathy in mice.
"Previous attempts to restore SERCA to prevent heart failure were unsuccessful because they focused on improving SERCA itself," explains Eric Olson, senior author and professor of stem cell research at Southwest Medical Center. "We believe that the improvement of dworf level may be more feasible, and the small size of dworf molecule may make it an attractive candidate for gene therapy drugs for heart failure."