Department of Pharmacology, School of Medicine, Universidad Complutense, Madrid, Spain.
PLoS One. 2010 Mar 22;5(3):e9800. doi: 10.1371/journal.pone.0009800.
We aimed to test the antiproliferative effect of acetylsalicylic acid (ASA) on vascular smooth muscle cells (VSMC) from bypass surgery patients and the role of transforming growth factor beta 1 (TGF-beta1).
METHODOLOGY/PRINCIPAL FINDINGS: VSMC were isolated from remaining internal mammary artery from patients who underwent bypass surgery. Cell proliferation and DNA fragmentation were assessed by ELISA. Protein expression was assessed by Western blot. ASA inhibited BrdU incorporation at 2 mM. Anti-TGF-beta1 was able to reverse this effect. ASA (2 mM) induced TGF-beta1 secretion; however it was unable to induce Smad activation. ASA increased p38(MAPK) phosphorylation in a TGF-beta1-independent manner. Anti-CD105 (endoglin) was unable to reverse the antiproliferative effect of ASA. Pre-surgical serum levels of TGF-beta1 in patients who took at antiplatelet doses ASA were assessed by ELISA and remained unchanged.
CONCLUSIONS/SIGNIFICANCE: In vitro antiproliferative effects of aspirin (at antiinflammatory concentration) on human VSMC obtained from bypass patients are mediated by TGF-beta1 and p38(MAPK). Pre-surgical serum levels of TGF- beta1 from bypass patients who took aspirin at antiplatelet doses did not change.
我们旨在测试乙酰水杨酸（ASA）对旁路手术患者血管平滑肌细胞（VSMC）的抗增殖作用及其转化生长因子β 1（TGF-β1）的作用。
方法/主要发现：从接受旁路手术的患者剩余的内乳动脉中分离出 VSMC。通过 ELISA 评估细胞增殖和 DNA 片段化。通过 Western blot 评估蛋白表达。ASA 在 2mM 时抑制 BrdU 掺入。抗 TGF-β1 能够逆转这种作用。ASA（2mM）诱导 TGF-β1 分泌；然而，它不能诱导 Smad 激活。ASA 以 TGF-β1 非依赖性方式增加 p38（MAPK）磷酸化。抗 CD105（内皮糖蛋白）无法逆转 ASA 的抗增殖作用。通过 ELISA 评估接受抗血小板剂量 ASA 的患者术前血清中 TGF-β1 的水平，并保持不变。
结论/意义：体外抗炎浓度的阿司匹林对旁路患者来源的人 VSMC 的抗增殖作用是通过 TGF-β1 和 p38（MAPK）介导的。接受抗血小板剂量 ASA 的旁路患者的术前血清 TGF-β1 水平没有变化。
