Andersson Emil, Zetterberg Eva, Vedin Inger, Hultenby Kjell, Palmblad Jan, Mints Miriam
Department of Women's and Children's Health, Karolinska Institutet at Karolinska University Hospital Solna, S-17176 Stockholm, Sweden.
Departments of Medicine and Hematology, Karolinska Institutet and Karolinska University Hospital Huddinge, S-14186 Stockholm, Sweden.
Int J Mol Med. 2015 Feb;35(2):433-8. doi: 10.3892/ijmm.2014.2035. Epub 2014 Dec 11.
A prospective clinical study was carried out to investigate whether endometrial microvessels in patients with idiopathic heavy menstrual bleeding (HMB) of endometrial origin (HMB-E) are fragile due to low pericyte coverage. Idiopathic HMB-E is characterized by large endothelial cell gaps related to the microvascular overexpression of vascular endothelial growth factor (VEGF)-A and VEGF receptors 1-3. A total of 10 women with a normal menstrual cycle and a history of HMB of <5 years, and 17 healthy women with a normal menstrual cycle were recruited from the Karolinska University Hospital. Blood samples were obtained for hormone analysis and coagulation tests. Endometrial biopsies were collected in the proliferative or in the secretory phase. Pericyte coverage was assessed using immunohistochemical staining for smooth muscle actin-α (SMAα) and by image analysis (microvascular density) of endometrial biopsies from 10 patients with HMB-E and 17 healthy ovulating women (control subjects). Previously published data on endothelial cell gap size and the expression of VEGF receptors were used. Although microvascular density did not differ between the patients with HMB-E and the control subjects, the number of SMAα-positive microvessels in the proliferative phase was significantly (P=0.005) lower in the patients with HMB-E than in the control subjects. Moreover, the number of SMAα-positive microvessels in the control subjects was significantly fewer in the secretory (P=0.04) than in the proliferative phase, whereas this number did not differ among the patients with HMB-E regardless of phase. A significant negative correlation was observed between the number of VEGF-A-positive microvessels and microvessels with pericyte coverage (r=0.8; P=0.04). Finally, the endothelial cell layer was significantly thicker in the patients with HMB-E than in the control subjects. Thus, the upregulation of VEGF-A in idiopathic HMB-E is associated with a low pericyte coverage during the proliferative phase of intense angiogenesis, which may confer vessel fragility, possibly leading to excessive blood loss.
开展了一项前瞻性临床研究，以调查子宫内膜源性特发性月经过多（HMB-E）患者的子宫内膜微血管是否因周细胞覆盖不足而脆弱。特发性HMB-E的特征是与血管内皮生长因子（VEGF）-A及VEGF受体1-3的微血管过表达相关的大内皮细胞间隙。从卡罗林斯卡大学医院招募了10名月经周期正常且有<5年HMB病史的女性，以及17名月经周期正常的健康女性。采集血样进行激素分析和凝血试验。在增殖期或分泌期采集子宫内膜活检组织。使用平滑肌肌动蛋白-α（SMAα）免疫组织化学染色和对10例HMB-E患者及17例健康排卵女性（对照对象）的子宫内膜活检组织进行图像分析（微血管密度）来评估周细胞覆盖情况。使用先前发表的关于内皮细胞间隙大小和VEGF受体表达的数据。尽管HMB-E患者与对照对象之间的微血管密度无差异，但HMB-E患者增殖期SMAα阳性微血管数量显著低于对照对象（P=0.005）。此外，对照对象分泌期SMAα阳性微血管数量显著少于增殖期（P=0.04），而HMB-E患者中该数量在各期无差异。观察到VEGF-A阳性微血管数量与有周细胞覆盖的微血管数量之间存在显著负相关（r=0.8；P=0.04）。最后，HMB-E患者的内皮细胞层显著厚于对照对象。因此，特发性HMB-E中VEGF-A的上调与强烈血管生成增殖期周细胞覆盖不足相关，这可能导致血管脆弱，进而可能导致失血过多。
