Induction of DNA synthesis by a single transient mechanical stimulus of human vascular smooth muscle cells - Role of fibroblast growth factor-2
Induction of DNA synthesis by a single transient mechanical stimulus of human vascular smooth muscle cells - Role of fibroblast growth factor-2
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DOI：
10.1161/01.cir.93.1.99
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发表时间：
1996-01-01
期刊：
影响因子：
37.8
通讯作者：
Lee, RT
中科院分区：
文献类型：
--
作者：
Cheng, GC;Libby, P;Lee, RT
背景虽然机械性血管损伤导致平滑肌细胞增殖，导致球囊血管成形术后的再狭窄，但平滑肌细胞的单一瞬时机械刺激在此过程中的作用尚不清楚。方法和结果为了检验单一瞬时机械刺激可以增加DNA合成的假设，对在三维胶原凝胶系统中培养的人血管平滑肌细胞进行瞬时压缩。在规定的无血清条件下，平滑肌细胞-胶原凝胶培养物的短暂压缩（持续5分钟）导致[H-3]胸苷掺入延迟增加。在压缩后12至24小时，存在3.3 +/- 0.5倍的（与对照组相比P <0.001）和3.0 +/- 0.6倍60%和80%菌株分别增加（与对照相比P <0.002）;在压缩后24至36小时，增加了1.8 +/-0.5倍（与对照相比P <0.05）和4.3 +/-0.8倍（与对照相比P <0.001）。此外，无血清培养基条件的瞬时压缩凝胶培养诱导DNA合成的控制，未受刺激的平滑肌细胞培养，这表明释放生长因子的瞬时压缩。虽然血小板源性生长因子的中和抗体不影响DNA合成的机械诱导，但抗成纤维细胞生长因子-2（FGF-2）的中和单克隆抗体可使这种诱导降低89%，并完全阻断由瞬时压缩凝胶条件培养基引起的DNA合成增加。通过瞬时压迫调节的培养基含有升高水平的FGF-2（17 +/- 5对对照组的2 +/- 2 pg/mL，P <0.005），乳酸脱氢酶活性没有增加，表明FGF-2的释放伴随亚致死细胞损伤。部分通过自分泌或旁分泌FGF-2释放。
Background Although mechanical vascular injury leads to smooth muscle cell proliferation that contributes to restenosis after balloon angioplasty, the role of the single transient mechanical stimulation of smooth muscle cells in this process is unknown.Methods and Results To test the hypothesis that a single transient mechanical stimulus can increase DNA synthesis, human vascular smooth muscle cells cultured in a three-dimensional collagen gel system were subjected to transient compression. Transient compression (5-minute duration) of smooth muscle cell-collagen gel cultures in defined serum-free conditions led to delayed increases in [H-3]thymidine incorporation. At 12 to 24 hours after compression, there was a 3.3 +/- 0.5-fold (P < .001 versus control) and 3.0 +/- 0.6-fold (P < .002 versus control) increase for 60% and 80% strain, respectively; at 24 to 36 hours after compression, there was a 1.8 +/- 0.5-fold (P < .05 versus control) and 4.3 +/- 0.8-fold (P < .001 versus control) increase. Also, serum-free media conditioned by transiently compressed gel cultures induced DNA synthesis in control, unstimulated smooth muscle cell cultures, suggesting the release of growth factors by transient compression. Although neutralizing antibodies against platelet-derived growth factor did not affect the mechanical Induction of DNA synthesis, a neutralizing monoclonal antibody against fibroblast growth factor-2 (FGF-2) decreased this induction by 89% and completely blocked the increase in DNA synthesis caused by media conditioned by transiently compressed gels. Media conditioned by transient compression contained elevated levels of FGF-2 (17 +/- 5 versus 2 +/- 2 pg/mL for control, P < .005) with no increase in lactate dehydrogenase activity, suggesting release of FGF-2 with sublethal cellular injury.Conclusions A single transient mechanical stimulus in creases DNA synthesis in human vascular smooth muscle cells, in part by autocrine or paracrine FGF-2 release.