Characterization of Intimal Smooth Muscle Precursor Cells in Circulating Human Peripheral Blood : Potential Origin of Intimal Smooth Muscle Cells in Vascular Lesions

循环人外周血中内膜平滑肌前体细胞的表征：血管病变中内膜平滑肌细胞的潜在起源

• 批准号: 14570679
• 负责人: SUGIYAMA Seigo
• 金额: $ 2.24万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570679/
• 关键词: atherosclerosis; blood cells; bone marrow; vascular smooth muscle cells; inflammation; precursor cells; surface antigen; human

Background Smooth muscle cells (SMC) play an important role in human vascular diseases. Several lines of evidence demonstrate that circulating smooth muscle precursor cells (SMPC) derived from bone marrow contribute to intimal hyperplasia in animal models.Methods and Results We obtained large spindle cells expressing smooth muscle a-actin (a-SMA), denoted here as "smooth muscle-like cells" (SMLC), from human peripheral blood mononuclear cells (PBMC). SMLC derived from human PBMC proliferated readily and had a pro-inflammatory phenotype during early culture. After maturation, SMLC could contract and express major SMC-markers. We discovered PBMC-expressing a-SMA in the circulating blood ; they exhibited a CD14(+)-CD105(+) phenotype. Sorted CD14-CD105 double-positive PBMC could differentiate into SMLC. The number of CD14-CD105-bearing PBMC increased significantly in patients with coronary artery disease (CAD) compared to patients without CAD.Conclusion These results support the novel concept that SMPC exist in circulating human blood and could potentially contribute to the pathogenesis of vascular diseases.

背景平滑肌细胞（Smooth muscle cells，SMC）在人类血管疾病中起重要作用。几条线的证据表明，来自骨髓的循环平滑肌前体细胞（SMPC）有助于内膜增生的动物models.Methods和结果我们获得了大梭形细胞表达平滑肌α-肌动蛋白（α-SMA），在这里表示为“平滑肌样细胞”（SMLC），从人外周血单核细胞（PBMC）。来源于人PBMC的SMLC在早期培养过程中容易增殖并具有促炎表型。成熟后，SMLC可以收缩并表达主要的SMC标记物。我们在循环血液中发现PBMC表达α-SMA;它们表现出CD 14（+）-CD 105（+）表型。分选后的CD 14-CD 105双阳性PBMC可分化为SMLC。冠心病患者外周血中CD 14-CD 105阳性PBMC的数量明显高于非冠心病患者。结论冠心病患者外周血中存在SMPC，SMPC可能参与了血管疾病的发生发展。

项目成果

Suzuki, S., Sugiyama, S., Usuku, H., Hirai, N., Kaikita, K., Sakashita, N., Sakamoto, T., Yoshimura, M., Ogawa, H.: "Heart failure with silent coronary artery spasm exhibiting microscopic focal myocardial necrosis and amyloid-deposition."Intern Med. 43(3)

Suzuki, S.、Sugiyama, S.、Usuku, H.、Hirai, N.、Kaikita, K.、Sakashita, N.、Sakamoto, T.、Yoshimura, M.、Okawa, H.：“无症状心力衰竭

Seigo Sugiyama, Osamu Honda, Kiyotaka Kugiyama, Hisao Ogawa: "Echotucent Carotid Plaques Predict Future Coronary Events an Patients with Coroanry Artery Disease"Journal of the American Collage of Cardiology. In press. (2004)

Seigo Sugiyama、Osamu Honda、Kiyotaka Kugiyama、Hisao Okawa：“回声颈动脉斑块预测冠状动脉疾病患者未来的冠状动脉事件”美国心脏病学院杂志。

Hironobu Fukushima, Seigo Sugiyama, Kiyotaka Kugiyama, Hisao Ogawa: "Prognostic value of remnant-like lipoprotein particles levels in patients with coronary artery disease and type 2 diabetes mellitus"Journal of the American Collage of Cardiology. (In pre

Hironobu Fukushima、Seigo Sugiyama、Kiyotaka Kugiyama、Hisao Okawa：“残余样脂蛋白颗粒水平对冠状动脉疾病和 2 型糖尿病患者的预后价值”美国心脏病学会杂志。

Koide, S., Kugiyama, K., Sugiyama, S., Nakamura, S., Fukushima, H., Honda, O., Yoshimura, M., Ogawa, H.: "Association of polymorphism in glutamate-cysteine ligase catalytic subunit gene with coronary vasomotor dysfunction and myocardial infarction."J Am C

小出，S.，Kugiyama，K.，杉山，S.，中村，S.，福岛，H.，本田，O.，吉村，M.，小川，H.：“谷氨酸半胱氨酸连接酶催化中多态性的关联

Nakamura, S., Sugiyama, S., Fujioka, D., Kawabata, K., Ogawa, H., Kugiyama, K.: "Polymorphism in glutamate-cysteine ligase modifier subunit gene is associated with impairment of nitric oxide-mediated coronary vasomotor function."Circulation. 108(12). 1425

Nakamura, S.、Sugiyama, S.、Fujioka, D.、Kawabata, K.、Okawa, H.、Kugiyama, K.：“谷氨酸半胱氨酸连接酶修饰子基因的多态性与一氧化氮介导的冠状动脉损伤有关