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Title: Knockout of AKAP150 improves impaired BK channel‐mediated vascular dysfunction through the Akt/GSK3β signalling pathway in diabetes mellitus

Journal Article · · Journal of Cellular and Molecular Medicine
DOI: https://doi.org/10.1111/jcmm.15143 · OSTI ID:1604256
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  1. Department of Cardiology Nanjing First Hospital Nanjing Medical University Nanjing China
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Abstract Vascular dysfunction resulting from diabetes is an important factor in arteriosclerosis. Previous studies have shown that during hyperglycaemia and diabetes, AKAP150 promotes vascular tone enhancement by intensifying the remodelling of the BK channel. However, the interaction between AKAP150 and the BK channel remains open to discussion. In this study, we investigated the regulation of impaired BK channel‐mediated vascular dysfunction in diabetes mellitus. Using AKAP150 null mice (AKAP150 −/− ) and wild‐type (WT) control mice (C57BL/6J), diabetes was induced by intraperitoneal injection of streptozotocin. We found that knockout of AKAP150 reversed vascular remodelling and fibrosis in mice with diabetes and in AKAP150 −/− diabetic mice. Impaired Akt/GSK3β signalling contributed to decreased BK‐β 1 expression in aortas from diabetic mice, and the silencing of AKAP150 increased Akt phosphorylation and BK‐β 1 expression in MOVAS cells treated with HG medium. The inhibition of Akt activity caused a decrease in BK‐β 1 expression, and treatment with AKAP150 siRNA suppressed GSK3β expression in the nuclei of MOVAS cells treated with HG. Knockout of AKAP150 reverses impaired BK channel‐mediated vascular dysfunction through the Akt/GSK3β signalling pathway in diabetes mellitus.

Sponsoring Organization:
USDOE
OSTI ID:
1604256
Journal Information:
Journal of Cellular and Molecular Medicine, Journal Name: Journal of Cellular and Molecular Medicine Journal Issue: 8 Vol. 24; ISSN 1582-1838
Publisher:
Wiley-BlackwellCopyright Statement
Country of Publication:
Country unknown/Code not available
Language:
English

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Arterial Stiffness Is Increased in Patients With Type 1 Diabetes Without Cardiovascular Disease: A potential role of low-grade inflammation journal February 2012
Long-term hyperglycaemia impairs vascular smooth muscle cell function in women with type 1 diabetes mellitus journal January 2009
Roles of A-Kinase Anchoring Proteins and Phosphodiesterases in the Cardiovascular System journal February 2018
Glycogen Synthase Kinase-3 (GSK-3)-Targeted Therapy and Imaging journal January 2016

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