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Impact of knockout of dual-specificity protein phosphatase 5 on structural and mechanical properties of rat middle cerebral arteries: implications for vascular aging

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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.

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The data supporting the findings of this study are available upon reasonable request from the corresponding author.

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Funding

This study was supported by grants AG079336, AG057842, P20GM104357, and HL138685 from the National Institutes of Health, and TRIBA Faculty Startup Fund from Augusta University.

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Author notes

  1. Chengyun Tang, Huawei Zhang, and Jane J. Border contributed equally to this work.

Authors and Affiliations

  1. Pharmacology & Toxicology, University of Mississippi Medical Center, Jackson, MS, USA

    Chengyun Tang, Huawei Zhang, Jane J. Border, Yedan Liu, Xing Fang, Joshua R. Jefferson, Richard J. Roman & Fan Fan

  2. Physiology, Medical College of Georgia, Augusta University, Augusta, GA, USA

    Chengyun Tang, Andrew Gregory, Claire Johnson & Fan Fan

  3. Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, Augusta, GA, USA

    Tae Jin Lee, Shan Bai & Ashok Sharma

  4. Anesthesiology, Medical College of Wisconsin, Milwaukee, WI, USA

    Seung Min Shin & Hongwei Yu

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  1. Chengyun Tang
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Contributions

HZ and FF conceived and designed research; HZ, CT, JB, YL, XF, and JRJ performed experiments; CT, HZ, JB, TJL, SB, AS, and FF analyzed data; CT, HZ, JB, RJR, and FF interpreted results; CT, HZ, JB, and FF prepared figures; CT, JB, HZ, and FF drafted the manuscript; CT, AG, CJ, TJL, SB, AS, SMS, HY, RJR, and FF edited and revised the manuscript; all authors approved the final version of the manuscript.

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Correspondence to Fan Fan.

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Tang, C., Zhang, H., Border, J.J. et al. Impact of knockout of dual-specificity protein phosphatase 5 on structural and mechanical properties of rat middle cerebral arteries: implications for vascular aging. GeroScience 46, 3135–3147 (2024). https://doi.org/10.1007/s11357-024-01061-y

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