Human aortic valve interstitial cells obtained from patients with aortic valve stenosis are vascular endothelial growth factor receptor 2 positive and contribute to ectopic calcification.
Human aortic valve interstitial cells obtained from patients with aortic valve stenosis are vascular endothelial growth factor receptor 2 positive and contribute to ectopic calcification.
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从主动脉瓣狭窄患者获得的人主动脉瓣间质细胞呈血管内皮生长因子受体 2 阳性，有助于异位钙化。
DOI：
10.1016/j.jphs.2020.12.002
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发表时间：
2021
影响因子：
3.5
通讯作者：
Seya Kazuhiko
中科院分区：
文献类型：
--
作者：
Liu Xu;Yu Zaiqiang;Daitoku Kazuyuki;Fukuda Ikuo;Motomura Shigeru;Matsumiya Tomoh;Imaizumi Tadaatsu;Furukawa Ken-Ichi;Seya Kazuhiko
主动脉瓣狭窄（aortic valve stenosis， AVS）是老年人最常见、最严重的瓣膜性心脏病，并伴有不可逆的瓣膜钙化，因此药物预防AVS具有重要意义。尽管我们最近证明，从AVS患者身上获得的人主动脉瓣间质细胞（HAVICs）对异位钙化刺激高度敏感，但导致钙化的细胞类型尚不清楚。我们的目的是免疫细胞化学表征havic，并确定其对瓣膜钙化的贡献。从AVS患者中分离haics并在无涂层培养皿中培养。传代1 （P1）分析免疫细胞化学特征和HAVIC分化。分析钙化主动脉瓣的免疫组织化学特征。大多数培养的P1 haics为CD73-， CD90-和cd105阳性，cd45和cd34阴性。血管内皮生长因子受体2 （VEGFR2）阳性；然而，大约一半是α-平滑肌肌动蛋白（SMA）阳性，定植，容易分化成成骨细胞。钙化主动脉瓣免疫组化显示所有细胞VEGFR2阳性，部分α-SMA阳性。此外，无论α-SMA阳性与否，vegfr2阳性细胞对肿瘤坏死因子-α-诱导的异位钙化更敏感。我们得出结论，从AVS患者获得的HAVICs是vegfr2阳性未分化间充质细胞，可能导致主动脉瓣异位钙化。
Since aortic valve stenosis (AVS) is the most frequent and serious valvular heart disease in the elderly, and is accompanied by irreversible valve calcification, medicinal prevention of AVS is important. Although we recently demonstrated that human aortic valve interstitial cells (HAVICs) obtained from patients with AVS were highly sensitive to ectopic calcification stimulation, the cell types contributing to calcification are unNnown. We aimed to immunocytochemically characterize HAVICs and identify their contribution to valve calcification. HAVICs were isolated from patients with AVS and cultured on non-coated dishes. Immunocytochemical features and HAVIC differentiation were analyzed in passage 1 (P1). The immunohistochemical features of the calcified aortic valve were analyzed. Most cultured P1 HAVICs were CD73-, CD90-, and CD105-positive, and CD45-and CD34-negative. HAVICs were vascular endothelial growth factor receptor 2 (VEGFR2)-positive; however, approximately half were α-smooth muscle actin (SMA)-positive, colonized, and easily differentiated into osteoblastic cells. Calcified aortic valve immunohistochemistry showed that all cells were positive for VEGFR2 and partly α-SMA. Further, VEGFR2-positive cells were more sensitive to tumor necrosis factor-α-induced ectopic calcification with or without α-SMA positivity. We conclude that HAVICs obtained from patients with AVS are VEGFR2-positive undifferentiated mesenchymal cells and may contribute to aortic valve ectopic calcification.