Multi-modal and multiscale imaging approaches reveal novel cardiovascular pathophysiology in Drosophila melanogaster

Weismann, Constance G.Lund University,Lunds universitet,Barnkardiologi,Forskargrupper vid Lunds universitet,Children cardiology,Lund University Research Groups,Skåne University Hospital,Yale University (författare)

Establishing connections between changes in linear DNA sequences and complex downstream mesoscopic pathology remains a major challenge in biology. Herein, we report a novel, multi-modal and multiscale imaging approach for comprehensive assessment of cardiovascular physiology in Drosophila melanogaster. We employed high-speed angiography, optical coherence tomography (OCT) and confocal microscopy to reveal functional and structural abnormalities in the hdp2 mutant, pre-pupal heart tube and aorta relative to controls. hdp2 harbor a mutation in wupA, which encodes an ortholog of human troponin I (TNNI3). TNNI3 variants frequently engender cardiomyopathy. We demonstrate that the hdp2 aortic and cardiac musclewalls are disrupted and that shorter sarcomeres are associated with smaller, stiffer aortas, which consequently result in increased flow and pulse wave velocities. The mutant hearts also displayed diastolic and latent systolic dysfunction.We conclude that hdp2 pre-pupal hearts are exposed to increased afterload due to aortic hypoplasia. This may in turn contribute to diastolic and subtle systolic dysfunction via vascular-heart tube interaction, which describes the effect of the arterial loading system on cardiac function. Ultimately, the cardiovascular pathophysiology caused by a point mutation in a sarcomeric protein demonstrates that complex and dynamic micro-and mesoscopic phenotypes can be mechanistically explained in a gene sequence-and molecular-specific manner.

Av författaren/redakt...: Weismann, Consta ...; Blice-Baum, Anna; Tong, Tangji; Li, Joyce; Huang, Brendan K ...; Jonas, Stephan M ...; visa fler...; Cammarato, Antho ...; Choma, Michael A ...; visa färre...

Om ämnet

MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Medicinska och f ...; och Medicinsk geneti ...

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.