Treating Dilated Cardiomyopathy with Methylene Blue Using the Drosophila melanogaster Heart Model

Dilated cardiomyopathy (DCM), the most common cardiomyopathy, is characterized by ventricular dilation and impaired heart contractility. Past studies found that the inhibition of the ubiquitin-proteasome system (UPS), a crucial protein degradation system that removes dysfunctional proteins, plays a key role in the pathogenesis of DCM. Since treatments for DCM only aim at alleviating heart failure symptoms, a new therapeutic was sought. Methylene blue (MB) was selected because of its cardioprotective properties and ability to increase proteasome activity, potentially allowing it to revert the impact of an impaired UPS. The Drosophila melanogaster strain wupA, which presents DCM symptoms, was used and treated with MB (30 μM). The flies’ lifespans and negative geotaxis were assessed, and dissections were conducted to analyze heart rates (HR), heart diameters, and fractional shortening (FS) with ImageJ. The log-rank test and t-tests were used to analyze statistical significance. Results showed that DCM increased the heart diameters (p<0.01) and decreased the HR (p<0.05), FS (p<0.01), and negative geotaxis (p<0.01). MB fully restored the dilated heart diameters and impaired FS as there was no significant difference between control and experimental groups (p>0.05), exhibiting potential in treating DCM. However, MB didn't affect the impaired HR and negative geotaxis of flies with DCM. Hence, future studies should investigate supplemental treatments to fully restore those properties.