Show simple item record

AuthorVono, Rosa
AuthorFuoco, Claudio
AuthorTesta, Stefano
AuthorPirrò, Stefano
AuthorMaselli, Davide
AuthorMcCollough, David Ferland
AuthorSangalli, Elena
AuthorPintus, Gianfranco
AuthorGiordo, Roberta
AuthorFinzi, Giovanna
AuthorSessa, Fausto
AuthorCardani, Rosanna
AuthorGotti, Ambra
AuthorLosa, Sergio
AuthorCesareni, Gianni
AuthorRizzi, Roberto
AuthorBearzi, Claudia
AuthorCannata, Stefano
AuthorSpinetti, Gaia
AuthorGargioli, Cesare
AuthorMadeddu, Paolo
Available date2016-10-16T06:35:43Z
Publication Date2016-09
Publication NameDiabetesen_US
Identifierhttp://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
ISSN0012-1797
URIhttp://hdl.handle.net/10576/4885
AbstractCritical 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.
Languageen
PublisherAmerican Diabetes Association
SubjectPericyte
SubjectDiabetic Patients
SubjectLimb Ischemia
SubjectOxidative Stress
TitleActivation of the Pro-Oxidant PKCβII-p66Shc Signaling Pathway Contributes to Pericyte Dysfunction in Skeletal Muscles of Diabetic Patients with Critical Limb Ischemia
TypeArticle
dc.identifier.essn 1939-327X


Files in this item

FilesSizeFormatView

There are no files associated with this item.

This item appears in the following Collection(s)

Show simple item record