title: Sirtuin 6 expression and inflammatory activity in diabetic atherosclerotic plaques: effects of incretin treatment.
abstract: The role of sirtuin 6 (SIRT6) in atherosclerotic progression of diabetic patients is unknown. We evaluated SIRT6 expression and the effect of incretin-based therapies in carotid plaques of asymptomatic diabetic and nondiabetic patients. Plaques were obtained from 52 type 2 diabetic and 30 nondiabetic patients undergoing carotid endarterectomy. Twenty-two diabetic patients were treated with drugs that work on the incretin system, GLP-1 receptor agonists, and dipeptidyl peptidase-4 inhibitors for 26 ± 8 months before undergoing the endarterectomy. Compared with nondiabetic plaques, diabetic plaques had more inflammation and oxidative stress, along with a lesser SIRT6 expression and collagen content. Compared with non-GLP-1 therapy-treated plaques, GLP-1 therapy-treated plaques presented greater SIRT6 expression and collagen content, and less inflammation and oxidative stress, indicating a more stable plaque phenotype. These results were supported by in vitro observations on endothelial progenitor cells (EPCs) and endothelial cells (ECs). Indeed, both EPCs and ECs treated with high glucose (25 mmol/L) in the presence of GLP-1 (100 nmol/L liraglutide) presented a greater SIRT6 and lower nuclear factor-κB expression compared with cells treated only with high glucose. These findings establish the involvement of SIRT6 in the inflammatory pathways of diabetic atherosclerotic lesions and suggest its possible positive modulation by incretin, the effect of which is associated with morphological and compositional characteristics of a potential stable plaque phenotype.
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Balestrieri
authors.affiliation: Department of Medical, Surgical, Neurological, Aging and Metabolic Sciences, Second University of Naples, Naples, Italy.
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Rizzo
authors.affiliation: Department of Medical, Surgical, Neurological, Aging and Metabolic Sciences, Second University of Naples, Naples, Italy.
authors.forename: Michelangela
authors.initials: M
authors.lastname: Barbieri
authors.affiliation: Department of Medical, Surgical, Neurological, Aging and Metabolic Sciences, Second University of Naples, Naples, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Paolisso
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy.
authors.forename: Nunzia
authors.initials: N
authors.lastname: D'Onofrio
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Giovane
authors.affiliation: Department of Cardiology, Cardarelli Hospital, Naples, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Siniscalchi
authors.affiliation: Department of Cardiology, Cardarelli Hospital, Naples, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Minicucci
authors.affiliation: Department of Medical, Surgical, Neurological, Aging and Metabolic Sciences, Second University of Naples, Naples, Italy.
authors.forename: Celestino
authors.initials: C
authors.lastname: Sardu
authors.affiliation: Department of Cardiology, Cardarelli Hospital, Naples, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: D'Andrea
authors.affiliation: Department of Cardiology, Cardarelli Hospital, Naples, Italy.
authors.forename: Ciro
authors.initials: C
authors.lastname: Mauro
authors.affiliation: Department of Clinical, Public and Preventive Medicine, Second University of Naples, Naples, Italy.
authors.forename: Franca
authors.initials: F
authors.lastname: Ferraraccio
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Servillo
authors.affiliation: Department of Neurosurgery, Cardarelli Hospital, Naples, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Chirico
authors.affiliation: Department of Neurosurgery, Cardarelli Hospital, Naples, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Caiazzo
authors.affiliation: Department of Medical, Surgical, Neurological, Aging and Metabolic Sciences, Second University of Naples, Naples, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Paolisso
authors.affiliation: Department of Medical, Surgical, Neurological, Aging and Metabolic Sciences, Second University of Naples, Naples, Italy raffaele.marfella@unina2.it.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Marfella
mesh_terms: D000368:Aged; D002339:Carotid Arteries / Q000187:drug effects* / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology*; D016894:Endarterectomy, Carotid; D005260:Female; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D054795:Incretins / Q000494:pharmacology*; D007249:Inflammation / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology; D058226:Plaque, Atherosclerotic / Q000378:metabolism*; D018027:Receptors, Glucagon / Q000819:agonists*; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism*
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D054795:Incretins; D018027:Receptors, Glucagon; D003094:Collagen; C516592:SIRT6 protein, human; D037761:Sirtuins