title: Short-term statin discontinuation increases endothelial progenitor cells without inflammatory rebound in type 2 diabetic patients.
abstract: Type 2 diabetes (T2D) is characterized by impaired vascular regeneration owing to reduced endothelial progenitor cells (EPCs). While statins are known to increase EPCs, the effects of statin withdrawal on EPCs are unknown. Herein, we evaluated the effects of statin discontinuation on EPCs, inflammation and in vivo angiogenesis. Thirty-four T2D patients were randomized to 5-day discontinuation or continuation of statin treatment. At baseline and at day 5, we determined lipid profile, EPC levels, monocyte-macrophage polarization, and concentrations of hsCRP, VEGF, SDF-1α, and G-CSF. Angiogenesis by human circulating cells was assessed in vivo. At day 5, patients who stopped statins showed raised total and LDL cholesterol and EPCs compared to baseline, while no changes were observed in patients who continued statins. No changes were observed in hsCRP, VEGF, SDF-1α, G-CSF, M1 and M2 macrophages and classical, intermediate and nonclassical monocytes in both groups. In vivo angiogenesis by circulating cells was increased in patients who stopped statin treatment. In vitro, cholesterol supplementation stimulated mobilizing signals in human bone marrow mesenchymal stem cells. In conclusion, a brief statin withdrawal increases circulating EPCs and functional proangiogenic cells in T2D. These findings identify statin-sensitive pathways as reverse target mechanisms to stimulate vascular repair in diabetes.
authors.affiliation: Department of Medicine, University of Padova, Italy; Venetian Institute of Molecular Medicine, Padova, Italy. Electronic address: gianpaolo.fadini@unipd.it.
authors.forename: Gian Paolo
authors.initials: GP
authors.lastname: Fadini
authors.affiliation: Department of Medicine, University of Padova, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Rigato
authors.affiliation: Department of Medicine, University of Padova, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Boscari
authors.affiliation: Department of Medicine, University of Padova, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Cappellari
authors.affiliation: Department of Medicine, University of Padova, Italy; Venetian Institute of Molecular Medicine, Padova, Italy.
authors.forename: Lisa
authors.initials: L
authors.lastname: Menegazzo
authors.affiliation: Department of Medicine, University of Padova, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Pilutti
authors.affiliation: Department of Medicine, University of Padova, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Iori
authors.affiliation: Department of Medicine, University of Padova, Italy.
authors.forename: Mariacristina
authors.initials: M
authors.lastname: Marescotti
authors.affiliation: Department of Medicine, University of Padova, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Plebani
authors.affiliation: Venetian Institute of Molecular Medicine, Padova, Italy.
authors.forename: Mattia
authors.initials: M
authors.lastname: Albiero
authors.affiliation: Department of Medicine, University of Padova, Italy; Venetian Institute of Molecular Medicine, Padova, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Avogaro
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002478:Cells, Cultured; D008078:Cholesterol, LDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D004334:Drug Administration Schedule; D066026:Endothelial Progenitor Cells / Q000187:drug effects* / Q000378:metabolism*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D007249:Inflammation / Q000097:blood / Q000175:diagnosis; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D013997:Time Factors
chemical_list: D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors
keywords: Angiogenesis; Lipids; Regeneration; Stem cells; Therapy