title: Endothelial progenitor cells are reduced in acromegalic patients and can be restored by treatment with somatostatin analogs.
abstract: BACKGROUND
  Acromegaly increases cardiovascular risk, possibly due to the high prevalence of classical risk factors. However, in vitro studies show a protective role of GH/IGF-1 on the endothelium.
  
  
  OBJECTIVE
  The objective of the study was to investigate circulating endothelial progenitor cells (EPCs), a marker of vascular regeneration, in acromegalic patients and how they are affected by acromegaly treatment.
  
  
  METHODS
  This was a cross-sectional case-control and observational study.
  
  
  METHODS
  The study was conducted at a tertiary ambulatory referral endocrinology center.
  
  
  METHODS
  Forty-three acromegalic patients (26 active; 17 inactive) and 43 control subjects matched by age, gender, and degree of glucose tolerance participated in the study.
  
  
  METHODS
  Circulating EPCs were quantified by flow cytometry based on the expression of CD34, CD133, and kinase insert domain-containing receptor (KDR). Nine patients with active acromegaly were reevaluated after 24 weeks of treatment with somatostatin analogs (SSAs).
  
  
  METHODS
  Differences in EPC levels between patients and controls were measured.
  
  
  RESULTS
  Acromegalic patients showed a significant reduction of the total CD34(+)KDR(+) EPC population compared with controls, which was more evident in patients without diabetes or hypertension. More definite CD34(+)CD133(+)KDR(+) EPCs were reduced in patients with active compared with those with inactive acromegaly and compared with controls. The number of CD34(+)CD133(+)KDR(+) EPCs correlated with IGF-1 levels (r = -0.45; P < .001), fasting plasma glucose (r = -0.40; P = .004), and the homeostasis model assessment index of insulin resistance (r = -0.32; P = .026). CD34(+)CD133(+)KDR(+) EPCs increased 2-fold after SSA treatment.
  
  
  CONCLUSIONS
  Acromegalic patients have a reduced endothelial regenerative capacity, possibly due to activation of the GH/IGF-1, rather than concomitant risk factors. Treatment with SSAs can restore immature EPCs to normal levels.
authors.affiliation: Department of Medicine (G.P.F., V.d.K., A.A.), Division of Metabolic Diseases, Laboratory of Experimental Diabetology (G.P.F., M.A., A.A.), Venetian Institute of Molecular Medicine, Department of Medicine (F.D., I.A., C.M., R.V., P.M.), Internal Medicine 3, Center for the Study and Integrated Therapy of Obesity, Endocrine-Metabolic Laboratory, and Department of Medicine, Immunology, and Hematology (E.B., C.A.), University of Padova, 35100 Padova, Italy.
authors.forename: Gian Paolo
authors.initials: GP
authors.lastname: Fadini
authors.forename: Francesca
authors.initials: F
authors.lastname: Dassie
authors.forename: Mattia
authors.initials: M
authors.lastname: Albiero
authors.forename: Elisa
authors.initials: E
authors.lastname: Boscaro
authors.forename: Irene
authors.initials: I
authors.lastname: Albano
authors.forename: Chiara
authors.initials: C
authors.lastname: Martini
authors.forename: Saula Vigili
authors.initials: SV
authors.lastname: de Kreutzenberg
authors.forename: Carlo
authors.initials: C
authors.lastname: Agostini
authors.forename: Angelo
authors.initials: A
authors.lastname: Avogaro
authors.forename: Roberto
authors.initials: R
authors.lastname: Vettor
authors.forename: Pietro
authors.initials: P
authors.lastname: Maffei
mesh_terms: D000172:Acromegaly / Q000473:pathology*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D042783:Endothelial Cells / Q000187:drug effects*; D005260:Female; D006727:Hormone Antagonists / Q000494:pharmacology*; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013234:Stem Cells / Q000187:drug effects*
chemical_list: D006727:Hormone Antagonists; D019382:Human Growth Hormone; D013004:Somatostatin; D007334:Insulin-Like Growth Factor I