Dataset Information

Zebrafish as a Model to Study Vascular Elastic Fibers and Associated Pathologies.

ABSTRACT: Many extensible tissues such as skin, lungs, and blood vessels require elasticity to function properly. The recoil of elastic energy stored during a stretching phase is provided by elastic fibers, which are mostly composed of elastin and fibrillin-rich microfibrils. In arteries, the lack of elastic fibers leads to a weakening of the vessel wall with an increased risk to develop cardiovascular defects such as stenosis, aneurysms, and dissections. The development of new therapeutic molecules involves preliminary tests in animal models that recapitulate the disease and whose response to drugs should be as close as possible to that of humans. Due to its superior in vivo imaging possibilities and the broad tool kit for forward and reverse genetics, the zebrafish has become an important model organism to study human pathologies. Moreover, it is particularly adapted to large scale studies, making it an attractive model in particular for the first steps of investigations. In this review, we discuss the relevance of the zebrafish model for the study of elastic fiber-related vascular pathologies. We evidence zebrafish as a compelling alternative to conventional mouse models.

SUBMITTER: Hoareau M

PROVIDER: S-EPMC8875079 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Zebrafish as a Model to Study Vascular Elastic Fibers and Associated Pathologies.

Hoareau Marie M El Kholti Naïma N Debret Romain R Lambert Elise E

International journal of molecular sciences 20220214 4

Many extensible tissues such as skin, lungs, and blood vessels require elasticity to function properly. The recoil of elastic energy stored during a stretching phase is provided by elastic fibers, which are mostly composed of elastin and fibrillin-rich microfibrils. In arteries, the lack of elastic fibers leads to a weakening of the vessel wall with an increased risk to develop cardiovascular defects such as stenosis, aneurysms, and dissections. The development of new therapeutic molecules invol ...[more]

PMID: 35216218

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Project description:Background - Chronic cerebral hypoperfusion (CCH) is an important pathophysiological mechanism of vascular cognitive impairment (VCI). The heterogeneous effects of CCH complicate establishing single target therapies against VCI and its more severe form, vascular dementia (VaD). Intermittent fasting (IF) has multiple targets and is neuroprotective across a range of disease conditions including stroke, but its effects against CCH-induced neurovascular pathologies remain to be elucidated. We therefore assessed the effect of IF against CCH-associated neurovascular pathologies and investigated its underlying mechanisms. Methods - Male C57BL/6NTac mice were subjected to either ad libitum feeding (AL) or IF (16 hours of fasting per day) for 4 months. In both groups, CCH was experimentally induced by the bilateral common carotid artery stenosis (BCAS) method. Sham operated groups were used as controls. Measures of leaky microvessels, blood-brain barrier (BBB) permeability, protein expression of tight junctions, extracellular matrix components and white matter changes were determined to investigate the effect of IF against CCH-induced neurovascular pathologies. Results - IF alleviated CCH-induced neurovascular pathologies by reducing the number of leaky microvessels, BBB breakdown and loss of tight junctional proteins. In addition, IF mitigated the severity of white matter lesions, and maintained myelin basic protein levels, while concurrently reducing hippocampal neuronal cell death. Furthermore, IF reduced the CCH-induced increase in levels of matrix metalloproteinase (MMP)-2 and its upstream activator MT1-MMP, which are involved in the breakdown of the extracellular matrix that is a core component of the BBB. Additionally, we observed that IF reduced CCH-induced increase in the oxidative stress marker malondialdehyde, and increased antioxidant markers glutathione and superoxide dismutase. Overall, our data suggest that IF attenuates neurovascular damage, metalloproteinase and oxidative stress-associated pathways, and cell death in the brain following CCH in a mouse model of VCI. Conclusion - Although IF has yet to be assessed in human patients with VaD, our data suggest that IF may be an effective means of preventing the onset or suppressing the development of neurovascular pathologies in VCI and VaD.

Dataset Information

Zebrafish as a Model to Study Vascular Elastic Fibers and Associated Pathologies.

Publications

Zebrafish as a Model to Study Vascular Elastic Fibers and Associated Pathologies.

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