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Aging and Chronic Disease (Poster Session)

(P18-023-24) Human Conserved Drosophila miR-6 Inhibition Has Profound Impact on Lipid Accumulation in the Heart While Mitigating Age-Related Cardiac Dysfunction

Monday, July 1, 2024
11:45 AM – 12:45 PM CT
Location: Poster Board 426
Disclosure(s):
Alyssa M. Hohman: No relevant financial relationship(s) with ineligible companies to disclose.


Objectives: Circulating miRNAs have been implicated in cardiovascular development and disease, and lipid metabolism, yet there are large gaps in our knowledge about their function in these diseased states. One of these microRNAs, mammalian miR-27, is well conserved with the Drosophila melanogaster microRNA, miR-6. Here, we use Drosophila as a model to investigate the role of this conserved regulatory mechanism.

Methods: Utilizing the miRNA sponge technology, we characterized the function of miR-6 loss on heart function, morphology, and lifespan. Functional and morphological changes to the heart were evaluated using SOHA (semi-automatic optical heartbeat analysis) software and immunohistochemistry. In silico analysis was conducted to determine the extent to which Drosophila miR-6 and mammalian miR-27 have maintained regulation over conserved genes, revealing many conserved predicted targets.

Results: We show heart-specific miR-6 inhibition mitigates age related increases in arrhythmia Index and heart diameter, and significantly extends lifespan, while also increasing lipid accumulation within the cardiomyocytes. We propose a mechanism through which miR-6 inhibition increases the abundance of low-density-lipoprotein-receptor-related protein 1 (LRP1) in the heart, which in turn leads to lipid accumulation.

Conclusions: Our results demonstrate that the mammalian conserved drosophila miR-6 plays a critical role in the metabolism of lipids in the heart and function with age. Seen in the lack of normal aging related changes to arrhythmia index and heart tube diameter, the increase in lifespan and the significant increase of lipids within cardiomyocytes. The conservation of miR-6 and its target genes enable us to discover the molecular mechanisms that underlie miRNA function in cardiovascular disease.

Funding Sources: American Heart Association Predoctoral Fellowship