Inhibition of protein kinase C beta phosphorylation activates nuclear factor-kappa B and improves postischemic recovery in type 1 diabetes.
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ABSTRACT: Impact statement
Diabetes worsens the outcomes of peripheral arterial disease (PAD) likely in part through inducing chronic inflammation. However, in PAD, recovery requires the nuclear factor-kappa B (NF-κB) activation, a known contributor to inflammation. Our study shows that individually, both ischemia and high glucose activate the canonical and non-canonical arms of the NF-κB pathways. We show for the first time that prolonged high glucose specifically impairs ischemia-induced activation of the canonical NF-κB pathway through activation of protein kinase C beta (PKCβ). Accordingly, inhibition of PKCβ restores the ischemia-induced NF-κB activity both in vitroin endothelial cells and in vivoin hind limbs of type 1 diabetic mice and improves perfusion recovery after experimental PAD. Thus, this study provides a mechanistic insight into how diabetes contributes to poor outcomes in PAD and a potential translational approach to improve PAD outcomes.
SUBMITTER: Alleboina S
PROVIDER: S-EPMC7273893 | biostudies-literature |
REPOSITORIES: biostudies-literature
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