Fibrin Gel Induces the Migration of Smooth Muscle Cells from Rabbit Aortic Explants
Fibrin Gel Induces the Migration of Smooth Muscle Cells from Rabbit Aortic Explants
复制标题
纤维蛋白凝胶诱导兔主动脉外植体平滑肌细胞的迁移
作者：
H. Nomura;A. Iguchi;W. Thompson;E. Smith;M. Naito
动脉粥样硬化发病的一个重要步骤是平滑肌细胞（SMCs）从动脉介质向内膜的矢量迁移。虽然传代培养的SMCs通常表现为合成表型，但收缩SMCs的行为可能对细胞的后续迁移至关重要。在本研究中，我们利用体外实验系统来评估纤维蛋白凝胶对兔主动脉外植体SMCs迁移的影响。在无血清条件下培养5-7天后，纤维蛋白凝胶覆盖的外植体出现了SMCs。细胞免疫染色显示SMC特异性α-肌动蛋白阳性。未添加纤维蛋白凝胶的对照外植体未观察到SMCs的迁移。随着时间的延长，出现细胞迁移的外植体的比例和迁移细胞的数量增加。SMCs向纤维蛋白凝胶的迁移不依赖于制备纤维蛋白凝胶所用纤维蛋白原的浓度在1.5 ~ 3mg /ml范围内。凝血酶浓度在0.25 ~ 1.25 U/ml范围内变化无显著影响。而凝血酶浓度越高，SMCs的迁移越少。凝血酶抑制剂、水蛭素和PPACK对SMCs的迁移无显著影响。作为一种含有rgd的肽，GRGDS抑制了SMCs的迁移，而相同浓度的对照肽GRGES则没有显著的影响。αvβ3单克隆抗体LM609完全抑制了SMCs从外植体向纤维蛋白凝胶的迁移，提示αvβ3整合素参与了SMCs向纤维蛋白凝胶的迁移。从外植体迁移而来的SMC肌球蛋白重链异构体SMemb、SM1和SM2单克隆抗体染色阳性，表明它们处于由收缩状态向合成状态转变的中间状态。综上所述，本研究表明，纤维蛋白凝胶诱导SMCs从外植体向自身迁移，这一过程可能不需要其他生长因子或细胞因子。
Summary A major step in the pathogenesis of atherosclerosis is the vectorial migration of smooth muscle cells (SMCs) from the arterial media into the intima. Although subcultured SMCs usually show synthetic phenotype, the behaviour of contractile SMCs may be crucial for the subsequent migration of the cells. In the present study, we utilized an in vitro assay system to evaluate the effects of fibrin gels on the migration of SMCs from explants taken from rabbit aorta. After cultured for 5-7 days in a serum-free condition, SMCs appeared from explants covered with fibrin gel. The cells were positive on immunostaining for SMC specific α-actin. No migration of SMCs from the control explants without fibrin gel was observed. Then the percentage of explants showing cell migration and the number of migrating cells increased with time. The migration of SMCs into fibrin gels was not dependent on the concentration of fibrinogen used for the preparation of fibrin gel in the range of 1.5-3 mg/ml. Variations of thrombin concentration in the range of 0.25-1.25 U/ml had no significant effect. However, there was less migration of SMCs with higher concentrations of thrombin. Thrombin inhibitors, hirudin and PPACK had no significant effect on the migration of SMCs. An RGD-containing peptide, GRGDS inhibited the migration of SMCs although a control peptide GRGES at the same concentration had no significant effect. A monoclonal antibody to αvβ3, LM609, completely inhibited the migration of SMCs from the explants, suggesting that αvβ3 integrin is involved in the migration of SMCs into fibrin gels. SMCs which migrated from the explants showed the positive staining with the monoclonal antibodies against SMC myosin heavy chain isoforms, SMemb, SM1 and SM2, suggesting that they are in an intermediate state changing from contractile to synthetic state. In conclusion, the present study showed that fibrin gel induces the migration of SMCs from explants into itself and the process may not need other growth factors or cytokines.
人类血栓和动脉粥样硬化病变中纤维蛋白原、纤维蛋白 I 和纤维蛋白 II 的免疫化学特征。
影响因子：
20.3
作者：
Bini,A;FenoglioJr,J;Sobel,J;Owen,J;Fejgl,M;Kaplan,KL
通讯作者：
Kaplan,KL
暴露于纤维蛋白单体和 FDP 的内皮细胞产生的 EDRF 受损。
DOI：
10.1152/ajpcell.1995.268.2.c520
发表时间：
1995
期刊：
The American journal of physiology.
影响因子：
--
作者：
Freedman,JE;Fabian,A;Loscalzo,J
通讯作者：
Loscalzo,J
纤维蛋白原降解产物片段 D 增加内皮单层通透性。
DOI：
10.1152/ajplung.1991.261.4.l283
发表时间：
1991
期刊：
The American journal of physiology
影响因子：
--
作者：
Ge,M;Ryan,TJ;Lum,H;Malik,AB
通讯作者：
Malik,AB