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.
J Clin Endocrinol Metab. 2014 Dec;99(12):E2549-56. doi: 10.1210/jc.2014-2275.
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.
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.
This was a cross-sectional case-control and observational study.
The study was conducted at a tertiary ambulatory referral endocrinology center.
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.
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).
Differences in EPC levels between patients and controls were measured.
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.
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.
肢端肥大症会增加心血管风险,这可能是由于常见风险因素的高发率所致。然而,体外研究表明 GH/IGF-1 对内皮具有保护作用。
本研究旨在探讨肢端肥大症患者循环中的内皮祖细胞(EPCs),即血管再生的标志物,以及它们如何受肢端肥大症治疗的影响。
这是一项横断面病例对照和观察性研究。
该研究在一家三级门诊内分泌学转诊中心进行。
43 例肢端肥大症患者(26 例活动期;17 例非活动期)和 43 例年龄、性别和血糖耐量匹配的对照组患者参与了研究。
通过流式细胞术基于 CD34、CD133 和激酶插入结构域受体(KDR)的表达来量化循环中的 EPC。9 例活动期肢端肥大症患者在接受生长抑素类似物(SSA)治疗 24 周后进行了重新评估。
测量患者和对照组之间 EPC 水平的差异。
与对照组相比,肢端肥大症患者的总 CD34(+)KDR(+)EPC 群体明显减少,在无糖尿病或高血压的患者中更为明显。与非活动期肢端肥大症患者和对照组相比,活动期肢端肥大症患者的更明确的 CD34(+)CD133(+)KDR(+)EPC 减少。CD34(+)CD133(+)KDR(+)EPC 数量与 IGF-1 水平(r = -0.45;P <.001)、空腹血浆葡萄糖(r = -0.40;P =.004)和胰岛素抵抗的稳态模型评估指数(r = -0.32;P =.026)呈负相关。SSA 治疗后 CD34(+)CD133(+)KDR(+)EPC 增加了 2 倍。
肢端肥大症患者的内皮再生能力降低,这可能是由于 GH/IGF-1 的激活,而不是伴随的风险因素。用 SSA 治疗可以使不成熟的 EPC 恢复到正常水平。