Fadini Gian Paolo, Dassie Francesca, Cappellari Roberta, Persano Mariasara, Vigili de Kreutzenberg Saula, Martini Chiara, Parolin Matteo, Avogaro Angelo, Vettor Roberto, Maffei Pietro
Department of Medicine, University of Padua, Padua 35128, Italy.
Venetian Institute of Molecular Medicine, Padua 35128, Italy.
J Clin Endocrinol Metab. 2017 Jun 1;102(6):2044-2050. doi: 10.1210/jc.2017-00246.
Acromegaly is a systemic disease characterized by persistent bone pathology and excess cardiovascular mortality. Despite multiple concomitant risk factors, atherosclerosis does not seem to be accelerated in acromegaly.
To compare the levels of circulating myeloid calcifying cells (MCCs), which promote ectopic calcification and inhibit angiogenesis, in individuals with and without acromegaly.
Cross-sectional case-control study.
Tertiary ambulatory referral endocrinology center.
44 acromegalic patients (25 active; 19 inactive), 44 control subjects matched by age, sex, risk factors, and medications, and 8 patients cured of acromegaly.
MCCs were measured using flow cytometry based on the expression of osteocalcin (OC) and bone alkaline phosphatase (BAP) on monocytes and circulating CD34+ stem cells.
Differences in MCCs between patients and controls.
OC+BAP+ MCCs were severely reduced in acromegalic compared with control patients (0.17% ± 0.02% vs 1.00% ± 0.24%; P < 0.001), as were the total OC+ and BAP+ monocytic cells. Patients with inactive acromegaly and those cured of acromegaly displayed persistently reduced levels of MCCs. In the controls, but not acromegalic patients, MCCs were increased in the presence of diabetes or cardiovascular disease. A direct correlation was noted between MCCs and parathyroid hormone (r = 0.61; P < 0.0001), supporting a link between bone biology and MCCs.
In patients with acromegaly, the levels of MCCs are reduced and remain low, even years after a complete cure. This finding might be related to low atherosclerotic calcification and the persistence of bone pathology after acromegaly remission or cure.
肢端肥大症是一种全身性疾病，其特征为持续性骨病变和心血管死亡率过高。尽管存在多种伴随风险因素，但肢端肥大症患者的动脉粥样硬化似乎并未加速。
比较患有和未患肢端肥大症的个体中循环髓样钙化细胞（MCCs）的水平，MCCs可促进异位钙化并抑制血管生成。
横断面病例对照研究。
三级门诊转诊内分泌中心。
44例肢端肥大症患者（25例活动期；19例非活动期）、44例按年龄、性别、风险因素和药物匹配的对照受试者，以及8例肢端肥大症已治愈的患者。
基于单核细胞和循环CD34+干细胞上骨钙素（OC）和骨碱性磷酸酶（BAP）的表达，使用流式细胞术测量MCCs。
患者与对照之间MCCs的差异。
与对照患者相比，肢端肥大症患者的OC+BAP+ MCCs严重减少（0.17%±0.02%对1.00%±0.24%；P<0.001），总OC+和BAP+单核细胞也是如此。非活动期肢端肥大症患者和肢端肥大症已治愈的患者MCCs水平持续降低。在对照受试者中，而非肢端肥大症患者中，糖尿病或心血管疾病患者的MCCs增加。MCCs与甲状旁腺激素之间存在直接相关性（r=0.61；P<0.0001），支持骨生物学与MCCs之间存在联系。
在肢端肥大症患者中，MCCs水平降低且持续处于低水平，即使在完全治愈数年之后也是如此。这一发现可能与动脉粥样硬化钙化程度低以及肢端肥大症缓解或治愈后骨病变持续存在有关。
