Impact of Knockout of Dual-Specificity Protein Phosphatase 5 on Structural and Mechanical Properties of Rat Middle Cerebral Arteries: Implications for Vascular Aging

Authors

Chengyun Tang
Huawei Zhang
Jane J Border
Yedan Liu
Xing Fang
Joshua R Jefferson
Andrew Gregory
Claire Johnson
Tae Jin Lee
Shan Bai
Ashok Sharma
Seung Min Shin
Hongwei Yu
Richard J Roman
Fan Fan

Publication Date

6-1-2024

Journal

Geroscience

Abstract

Vascular aging influences hemodynamics, elevating risks for vascular diseases and dementia. We recently demonstrated that knockout (KO) of Dusp5 enhances cerebral and renal hemodynamics and cognitive function. This improvement correlates with elevated pPKC and pERK1/2 levels in the brain and kidneys. Additionally, we observed that Dusp5 KO modulates the passive mechanical properties of cerebral and renal arterioles, associated with increased myogenic tone at low pressure, enhanced distensibility, greater compliance, and reduced stiffness. The present study evaluates the structural and mechanical properties of the middle cerebral artery (MCA) in Dusp5 KO rats. We found that vascular smooth muscle cell layers and the collagen content in the MCA wall are comparable between Dusp5 KO and control rats. The internal elastic lamina in the MCA of Dusp5 KO rats exhibits increased thickness, higher autofluorescence intensity, smaller fenestrae areas, and fewer fenestrations. Despite an enhanced myogenic response and tone of the MCA in Dusp5 KO rats, other passive mechanical properties, such as wall thickness, cross-sectional area, wall-to-lumen ratio, distensibility, incremental elasticity, circumferential wall stress, and elastic modulus, do not significantly differ between strains. These findings suggest that while Dusp5 KO has a limited impact on altering the structural and mechanical properties of MCA, its primary role in ameliorating hemodynamics and cognitive functions is likely attributable to its enzymatic activity on cerebral arterioles. Further research is needed to elucidate the specific enzymatic mechanisms and explore potential clinical applications in the context of vascular aging.

Keywords

Animals, Rats, Aging, Brain, Cognition, Dual-Specificity Phosphatases, Middle Cerebral Artery

Comments

Data Availability Statement

PMID: 38200357