Endothelial progenitor cells are reduced in acromegalic patients and can be restored by treatment with somatostatin analogs

J Clin Endocrinol Metab. 2014 Dec;99(12):E2549-56. doi: 10.1210/jc.2014-2275.

Abstract

Context: 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.

Design: This was a cross-sectional case-control and observational study.

Setting: The study was conducted at a tertiary ambulatory referral endocrinology center.

Patients: 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.

Intervention: 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).

Main outcome measure: 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.

Publication types

  • Observational Study

MeSH terms

  • Acromegaly / pathology*
  • Case-Control Studies
  • Cross-Sectional Studies
  • Endothelial Cells / drug effects*
  • Female
  • Hormone Antagonists / pharmacology*
  • Human Growth Hormone / blood
  • Humans
  • Insulin-Like Growth Factor I / metabolism
  • Male
  • Middle Aged
  • Somatostatin / analogs & derivatives*
  • Somatostatin / pharmacology*
  • Stem Cells / drug effects*

Substances

  • Hormone Antagonists
  • Human Growth Hormone
  • Somatostatin
  • Insulin-Like Growth Factor I