Investigating cardiovascular mechanotransduction: insights from cardiac models under simulated microgravity and radiation

Basirun, Carin Alsani

Investigating cardiovascular mechanotransduction: insights from cardiac models under simulated microgravity and radiation

Basirun, Carin Alsani

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Publication Type:: Thesis
Issue Date:: 2024

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Field	Value	Language
dc.contributor.author	Basirun, Carin Alsani
dc.date.accessioned	2025-04-03T03:49:06Z
dc.date.available	2025-04-03T03:49:06Z
dc.date.issued	2024
dc.identifier.uri	http://hdl.handle.net/10453/186553
dc.description	University of Technology Sydney. Faculty of Engineering and Information Technology.	en_US.UTF-8
dc.description.abstract	This thesis investigates the effects of simulated microgravity (s-µG) and ionizing radiation (IR) on cardiomyocytes using both two-dimensional (2D) and three-dimensional (3D) culture models to understand the impact of spaceflight conditions on cardiovascular health. The primary aim is to elucidate how these stressors influence cellular behaviour, mechanotransduction pathways, and DNA damage responses. The first aim characterised the initial responses of AC-16 cardiomyocytes to s-µG, IR, and their combined effects in a 2D environment. Methods included cell viability assays, gene expression analysis, and DNA damage assessment through γ-H2AX foci formation. Results showed decreased cell proliferation and viability under s-µG, with IR causing notable DNA damage. Combined exposure exacerbated DNA damage without additive effects on YAP1 nuclear localization. The second aim developed a 3D collagen-based hydrogel for studying cardiomyocyte responses. Methods included fabrication of 3D hydrogels, cell embedding, and viability assays under s-µG and IR conditions. Preliminary results indicated the 3D environment buffered gene expression changes and enhanced cell viability compared to 2D cultures. However, combined s-µG and IR exposure significantly increased DNA damage. The third aim optimized 3D bioprinting techniques to create a hybrid heart-on-a-chip model for simulating the cardiac microenvironment. Techniques included using bioinks and incorporating human cardiac fibroblasts. Assessments revealed significant findings related to cell viability, proliferation, and functionality under s-µG and IR conditions, demonstrating the model's potential for studying spaceflight-induced cardiovascular risks. In conclusion, this thesis advanced our understanding of cardiomyocyte behaviour under spaceflight like conditions and developed innovative models for future investigations. The insights gained will inform strategies to protect cardiovascular health in space, ensuring astronaut safety on extended missions. Through comprehensive evaluation of s-µG and IR effects in both 2D and 3D environments, this research lays a foundation for future studies aimed at mitigating space travel health risks	en_US.UTF-8
dc.format	Thesis (PhD)
dc.language.iso	en_US	en_US.UTF-8
dc.relation	https://opus.lib.uts.edu.au/bitstream/10453/186553/1/thesis.pdf
dc.rights	info:eu-repo/semantics/openAccess
dc.rights	The author owns the copyright in this thesis including all reproduction and reuse rights for the work. The work may not be altered without the permission of the copyright owner. Attribution is essential when quoting or paraphrasing from this thesis.
dc.rights	© 2024 Carin Alsani Basirun
dc.rights	au.edu.uts.lib/nph
dc.title	Investigating cardiovascular mechanotransduction: insights from cardiac models under simulated microgravity and radiation	en_US.UTF-8
dc.type	Thesis
utslib.copyright.status	open_access	*

Abstract:

This thesis investigates the effects of simulated microgravity (s-µG) and ionizing radiation (IR) on cardiomyocytes using both two-dimensional (2D) and three-dimensional (3D) culture models to understand the impact of spaceflight conditions on cardiovascular health. The primary aim is to elucidate how these stressors influence cellular behaviour, mechanotransduction pathways, and DNA damage responses. The first aim characterised the initial responses of AC-16 cardiomyocytes to s-µG, IR, and their combined effects in a 2D environment. Methods included cell viability assays, gene expression analysis, and DNA damage assessment through γ-H2AX foci formation. Results showed decreased cell proliferation and viability under s-µG, with IR causing notable DNA damage. Combined exposure exacerbated DNA damage without additive effects on YAP1 nuclear localization. The second aim developed a 3D collagen-based hydrogel for studying cardiomyocyte responses. Methods included fabrication of 3D hydrogels, cell embedding, and viability assays under s-µG and IR conditions. Preliminary results indicated the 3D environment buffered gene expression changes and enhanced cell viability compared to 2D cultures. However, combined s-µG and IR exposure significantly increased DNA damage. The third aim optimized 3D bioprinting techniques to create a hybrid heart-on-a-chip model for simulating the cardiac microenvironment. Techniques included using bioinks and incorporating human cardiac fibroblasts. Assessments revealed significant findings related to cell viability, proliferation, and functionality under s-µG and IR conditions, demonstrating the model's potential for studying spaceflight-induced cardiovascular risks. In conclusion, this thesis advanced our understanding of cardiomyocyte behaviour under spaceflight like conditions and developed innovative models for future investigations. The insights gained will inform strategies to protect cardiovascular health in space, ensuring astronaut safety on extended missions. Through comprehensive evaluation of s-µG and IR effects in both 2D and 3D environments, this research lays a foundation for future studies aimed at mitigating space travel health risks

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http://hdl.handle.net/10453/186553