Activation of the Pro-Oxidant PKCβII-p66Shc Signaling Pathway Contributes to Pericyte Dysfunction in Skeletal Muscles of Diabetic Patients with Critical Limb Ischemia
Author | Vono, Rosa |
Author | Fuoco, Claudio |
Author | Testa, Stefano |
Author | Pirrò, Stefano |
Author | Maselli, Davide |
Author | McCollough, David Ferland |
Author | Sangalli, Elena |
Author | Pintus, Gianfranco |
Author | Giordo, Roberta |
Author | Finzi, Giovanna |
Author | Sessa, Fausto |
Author | Cardani, Rosanna |
Author | Gotti, Ambra |
Author | Losa, Sergio |
Author | Cesareni, Gianni |
Author | Rizzi, Roberto |
Author | Bearzi, Claudia |
Author | Cannata, Stefano |
Author | Spinetti, Gaia |
Author | Gargioli, Cesare |
Author | Madeddu, Paolo |
Available date | 2016-10-16T06:35:43Z |
Publication Date | 2016-09 |
Publication Name | Diabetes |
Identifier | http://dx.doi.org/10.2337/db16-0248 |
Citation | "Activation of the Pro-Oxidant PKCβII-p66Shc Signaling Pathway Contributes to Pericyte Dysfunction in Skeletal Muscles of Diabetic Patients with Critical Limb Ischemia" Rosa Vono, Claudia Fuoco, Stefano Testa, Stefano Pirrò, Davide Maselli, David Ferland Mc Collough, Elena Sangalli, Gianfranco Pintus, et al. Diabetes Sep 2016, db160248 |
ISSN | 0012-1797 |
Abstract | Critical limb ischemia (CLI), foot ulcers, former amputation and impaired regeneration are independent risk factors for limb amputation in diabetic subjects. The present work investigates whether and by which mechanism diabetes negatively impacts on functional properties of muscular pericytes (MPs), which are resident stem cells committed to reparative angiomyogenesis. We obtained muscle biopsies from diabetic patients undergoing major limb amputation and control subjects. Diabetic muscles collected at the rim of normal tissue surrounding the plane of dissection showed myofibres degeneration, fat deposition, and reduction of MPs vascular coverage. Diabetic MPs (D-MPs) display ultrastructural alterations, a differentiation bias towards adipogenesis at the detriment of myogenesis and an inhibitory activity on angiogenesis. Furthermore, they have an imbalanced redox state, with down-regulation of the anti-oxidant enzymes SOD-1 and catalase and activation of the pro-oxidant PKCβII-dependent p66Shc signaling pathway. A reactive oxygen species scavenger or, even more effectively, clinically-approved PKCβII inhibitors restore D-MPs angiomyogenic activity.Inhibition of the PKCβII-dependent p66Shc signaling pathway could represent a novel therapeutic approach for promotion of muscle repair in diabetes. |
Language | en |
Publisher | American Diabetes Association |
Subject | Pericyte Diabetic Patients Limb Ischemia Oxidative Stress |
Type | Article |
ESSN | 1939-327X |
Files in this item
Files | Size | Format | View |
---|---|---|---|
There are no files associated with this item. |
This item appears in the following Collection(s)
-
Biomedical Sciences [697 items ]