Low-dose growth hormone administration mobilizes endothelial progenitor cells in healthy adults.

Department of Endocrine Neoplasia and Hormonal Disorders, 1400 Holcombe Blvd. Unit 435, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, United States.
Growth Hormone & IGF Research (Impact Factor: 1.33). 07/2008; 18(3):253-63. DOI: 10.1016/j.ghir.2007.11.001
Source: PubMed

ABSTRACT Endothelial progenitor cells (EPCs) mobilize from the bone marrow secondary to a stimulus and home to sites of injury, where they differentiate into endothelial cells and contribute to the repair of damaged vasculature. We hypothesized that growth hormone (GH) administration would increase the number of circulating EPCs in adults and thereby represent a mechanism to enhance vascular health.
A prospective trial of low-dose GH (0.03mg/kg/week for 4 weeks followed by 0.06mg/kg/week for a maximum of four additional weeks) in 10 healthy adults (6 males and 4 females; mean age 37 years, range 26-65). Primary outcomes measured included the number of circulating EPCs as assessed by colony-forming unit (CFU) assay and flow cytometry. Secondary outcomes included plasma measurements of known mediators of EPC mobilization and indices of nitric oxide (NO). Outcomes were measured at baseline and at study completion.
GH administration increased serum IGF-1 (143ng/mL [IQR 121-164] to 222 [IQR 194-244]; P=0.005). The increase in early-outgrowth EPCs (13 CFU per high-power field [IQR 6-24] to 19 [IQR 13-40]; P=0.005) correlated with the peak IGF-1 after adjustment for the baseline number of early-outgrowth EPCs (r=0.719 [95% CI 0.06, 0.93]; P=0.027). The number of late-outgrowth EPCs as well as CD34+, VEGFR2(KDR)+, and AC133+ cells did not significantly change. Other mediators of EPC mobilization were stable while plasma nitrite trended upwards (1.3micromol/L [IQR 0-2.5] to 3.7 [IQR 2.2-8.9]; P=0.052).
GH administration selectively augments the early-outgrowth EPC population in healthy individuals. These findings both support GH replacement in the setting of GH deficiency to maintain vascular integrity and have implications for the use of GH in future regenerative cell-based therapies. Furthermore, the decrease in EPCs observed with aging may in part be explained by the declining somatotropic axis, and thereby contribute to cardiovascular senescence.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Patients with Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus (SLE) have a significantly increased risk of cardiovascular disease (CVD). The reason for this is unclear but may be due, at least in part, to the failure of endothelial repair mechanisms. Over the last 15years there has been much interest in the mechanisms of endothelial renewal and its potential as a therapy for CVD. In the circulation there are two distinct populations of cells; myeloid angiogenic cells (MACs) which augment repair by the paracrine secretion of angiogenic factors, and outgrowth endothelial cells (OECs) which are true endothelial progenitor cells (EPCs) and promote vasculogenesis by differentiating into mature endothelium. There are marked abnormalities in the number and function of these cells in patients with RA and SLE. Inflammatory cytokines including interferon-alpha (IFNα) and tumour-necrosis factor alpha (TNFα) both impair MAC and OEC function ex vivo and may therefore contribute to the CVD risk in these patients. Whilst administration of mononuclear cells, MACs and other progenitors has improved cardiovascular outcomes in the acute setting, this is not a viable option in chronic disease. The pharmacological manipulation of MAC/OEC function in vivo however has the potential to significantly improve endothelial repair and thus reduce CVD in this high risk population.
    Pharmacology [?] Therapeutics 12/2013; DOI:10.1016/j.pharmthera.2013.12.008 · 7.75 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Endothelial progenitor cells (EPCs), involved in the repairing mechanisms of vascular damage, are positively correlated to IGF-1 concentrations in healthy adults. However, the levels of EPCs and their role in acromegalic patients have never been investigated. Aim: We conducted a cross-sectional study in order to assess the levels of the different phenotypes of circulating EPC in acromegalic patients. Subjects and methods: The study was performed at the Endocrinology Unit of Federico II University and at the Unit of Metabolic Diseases and Endocrinology of the Second University of Naples. Fifty-five acromegalic patients and 65 healthy controls were studied. EPCs were assessed by flow cytometry and IGF-1 by IRMA. Results: Compared with subjects of the control group, acromegalic patients showed significantly higher levels of EPCs phenotypes expressing KDR antigen, (KDR+, cells per 106 events, median and interquartile range, 44 [28-67] vs 23 [13-40] P=0.006; CD34+KDR+ 25 [18-38] vs 12 [8-17] P <0.001; CD133+KDR+ 17 [13-30] vs 8 [6-12] P <0.001; CD34+KDR+CD133+ 16 [12-25] vs 8 [6-10] P <0.001). There was a positive correlations between CD34+KDR+CD133+ cells count and IGF-1 in acromegaly group (r = 0.79, P <0.001). Conclusions: Acromegalic patients show higher circulating EPCs levels expressing KDR, positively correlated with IGF1, suggesting a role for IGF-1 in regulating the expression of this surface marker in the early phase of EPCs differentiation.
    Journal of endocrinological investigation 06/2013; 36(10). DOI:10.3275/9020 · 1.55 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: IGF-1 is a potent mitogen for vascular smooth muscle cells, but exerts protective effects on endothelial cells that may trigger antiatherogenic mechanisms. Objectives: This study was designed to test the hypothesis that an IGF-1 excess following arterial injury prevents neointima formation and vascular stenosis. Methods: Rats were subjected to carotid balloon injury and treated with IGF-1 (1.2 mg kg−1 per die) or saline for 10 days. Results: In IGF-1 treated animals, high tissue levels of eNOS, Akt and its phosphorylated form were found, confirming activation of IGF-1-dependent signaling pathways. IGF-1 markedly reduced neointima formation and post-injury arterial stenosis. IGF-1 exerted proliferative and anti-apoptotic effects in the media of injured carotids, but inhibited mitotic activity and induced apoptosis in the neointima. Furthermore, IGF-1 stimulated mobilization of progenitor endothelial cells and re-endothelialization of the injured arteries. L-NAME administration inhibited IGF-1 vasculoprotective effects. Conclusions: IGF-1 attenuates post-injury carotid stenosis by exerting differential effects in the neointima and tunica media with regard to the key components of the response to injury. The data point to a novel role of IGF-1 as a potent vasculoprotective factor.
    Journal of Thrombosis and Haemostasis 10/2009; 7(11):1920 - 1928. DOI:10.1111/j.1538-7836.2009.03607.x · 5.55 Impact Factor