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

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• 作者：Jessica K. Devin ; Douglas E. Vaughan ; Lewis S. Blevins Jr. ; Qingxia Chen ; Joseph Covington ; Denise K. Verity ; Pampee P. Young
• 关键词：Growth hormone ; Insulin-like growth factor 1 ; Angiogenesis ; Aging ; Endothelial function ; Endothelial progenitor cells
• 刊名：Growth Hormone IGF Research
• 出版年：2008
• 出版时间：June 2008
• 年：2008
• 卷：18
• 期：3
• 页码：253-263
• 全文大小：342 K

文摘

ass=""h4"">Objective

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.

ass=""h4"">Design

A prospective trial of low-dose GH (0.03 mg/kg/week for 4 weeks followed by 0.06 mg/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.

ass=""h4"">Results

GH administration increased serum IGF-1 (143 ng/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 (1.3 μmol/L [IQR 0–2.5] to 3.7 [IQR 2.2–8.9]; P = 0.052).

ass=""h4"">Conclusions

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.