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Isolation and Functional Analysis of Arteriolar Endothelium of Mouse Brain Parenchyma
Published on: March 11, 2022
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Enhanced age-dependent cerebrovascular dysfunction is mediated by adaptor protein p66Shc
Yi Shi1, Gianluigi Savarese2, Pasquale Perrone-Filardi3
1Center of Molecular Cardiology, University of Zurich, Zurich, Switzerland; Zurich Center for Integrative Human Physiology (ZHIP), University of Zurich, Zurich, Switzerland; Biomedical Research Center, Zhongshan Hospital, Fudan University, Shanghai, China.
International Journal of Cardiology
|July 12, 2014
Summary
Aging impairs cerebral artery function, but not systemic arteries, due to increased reactive oxygen species (ROS) mediated by the p66Shc gene. This study reveals a key mechanism in age-related vascular dysfunction.
Area of Science:
- Vascular Biology
- Aging Research
- Genetics
Background:
- Aging is a significant risk factor for cardiovascular and cerebrovascular diseases.
- Mechanisms of cerebral artery aging and the role of the p66Shc gene are not well understood.
Purpose of the Study:
- To investigate age-induced vascular dysfunction in cerebral and systemic arteries of wild-type (wt) and p66Shc knockout (p66Shc-/-) mice.
- To determine if the p66Shc gene is involved in the aging of cerebral arteries.
Main Methods:
- Vascular function assessment in basilar and femoral arteries from mice of different ages (3 months, 6 months, 2 years).
- Isometric tension recordings and exposure to acetylcholine and sodium nitroprusside.
- Measurement of reactive oxygen species (ROS) generation using electron paramagnetic resonance (EPR) spectroscopy.
Main Results:
- Age-dependent endothelial dysfunction was observed in basilar arteries of wt mice but not femoral arteries.
- Endothelial dysfunction in basilar arteries was blunted in p66Shc-/- mice compared to wt mice.
- Age-associated increase in ROS levels was found in basilar arteries of wt mice, but not in p66Shc-/- mice.
Conclusions:
- Aging significantly impairs endothelial function in cerebral arteries, unlike in systemic arteries.
- Increased ROS production in cerebral arteries during aging is mediated by the p66Shc gene.
- The p66Shc gene plays a crucial role in age-related endothelial dysfunction of cerebral arteries.
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