Multi-modal and multiscale imaging approaches reveal novel cardiovascular pathophysiology in Drosophila melanogaster
Weismann, Constance G. LU
; Blice-Baum, Anna
; Tong, Tangji
; Li, Joyce
; Huang, Brendan K.
; Jonas, Stephan M.
; Cammarato, Anthony
and Choma, Michael A.
(2019)
In Biology Open
8(8).
- Abstract
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... (More)
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.
(Less)
- author
- Weismann, Constance G.
LU
; Blice-Baum, Anna
; Tong, Tangji
; Li, Joyce
; Huang, Brendan K.
; Jonas, Stephan M.
; Cammarato, Anthony
and Choma, Michael A.
- organization
- publishing date
- 2019
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Aortic stiffness, Cardiovascular physiology, Drosophila melanogaster, hdp, OCT, Troponin
- in
- Biology Open
- volume
- 8
- issue
- 8
- article number
- bio044339
- publisher
- The Company of Biologists Ltd
- external identifiers
-
- scopus:85071879345
- pmid:31455664
- ISSN
- 2046-6390
- DOI
- 10.1242/bio.044339
- language
- English
- LU publication?
- yes
- id
- 9a00b405-af39-42b9-a6ef-eea6b14e622d
- date added to LUP
- 2019-09-18 15:18:58
- date last changed
- 2024-04-30 22:01:23
@article{9a00b405-af39-42b9-a6ef-eea6b14e622d,
abstract = {{<p>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.</p>}},
author = {{Weismann, Constance G. and Blice-Baum, Anna and Tong, Tangji and Li, Joyce and Huang, Brendan K. and Jonas, Stephan M. and Cammarato, Anthony and Choma, Michael A.}},
issn = {{2046-6390}},
keywords = {{Aortic stiffness; Cardiovascular physiology; Drosophila melanogaster; hdp; OCT; Troponin}},
language = {{eng}},
number = {{8}},
publisher = {{The Company of Biologists Ltd}},
series = {{Biology Open}},
title = {{Multi-modal and multiscale imaging approaches reveal novel cardiovascular pathophysiology in Drosophila melanogaster}},
url = {{http://dx.doi.org/10.1242/bio.044339}},
doi = {{10.1242/bio.044339}},
volume = {{8}},
year = {{2019}},
}