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Published October 2018 | Accepted Version
Journal Article Open

Advanced microscopy to elucidate cardiovascular injury and regeneration: 4D light-sheet imaging

Abstract

The advent of 4-dimensional (4D) light-sheet fluorescence microscopy (LSFM) has provided an entry point for rapid image acquisition to uncover real-time cardiovascular structure and function with high axial resolution and minimal photo-bleaching/-toxicity. We hereby review the fundamental principles of our LSFM system to investigate cardiovascular morphogenesis and regeneration after injury. LSFM enables us to reveal the micro-circulation of blood cells in the zebrafish embryo and assess cardiac ventricular remodeling in response to chemotherapy-induced injury using an automated segmentation approach. Next, we review two distinct mechanisms underlying zebrafish vascular regeneration following tail amputation. We elucidate the role of endothelial Notch signaling to restore vascular regeneration after exposure to the redox active ultrafine particles (UFP) in air pollutants. By manipulating the blood viscosity and subsequently, endothelial wall shear stress, we demonstrate the mechanism whereby hemodynamic shear forces impart both mechanical and metabolic effects to modulate vascular regeneration. Overall, the implementation of 4D LSFM allows for the elucidation of mechanisms governing cardiovascular injury and regeneration with high spatiotemporal resolution.

Additional Information

© 2018 Elsevier Ltd. Received 31 January 2018, Revised 30 April 2018, Accepted 4 May 2018, Available online 9 May 2018. This study was supported by the National Institutes of Health HL118650 (T.K.H.), HL083015 (T.K.H.), HL111437 (T.K.H.), HL129727 (T.K.H.), T32 training grant HL007895 (J.J.H.), and an AHA Scientist Development Grant 16SDG30910007 (R.R.S.P). The authors have no conflict of interest to disclose.

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August 22, 2023
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October 18, 2023