冠状动脉血管成形术后人和小型猪平滑肌细胞对生长因子及血小板的增殖反应

Proliferative response of human and minipig smooth muscle cells after coronary angioplasty to growth factors and platelets.

作者信息

Unterberg C, Meyer T, Wiegand V, Kreuzer H, Buchwald A B

机构信息

Department of Cardiology and Pulmonology, University Clinic, Göttingen, FRG.

出版信息

Basic Res Cardiol. 1996 Nov-Dec;91(6):407-17. doi: 10.1007/BF00788721.

DOI:10.1007/BF00788721

PMID:8996625

Abstract

OBJECTIVES

Platelets aggregating at the site of angioplasty, shown to be a potent proliferative stimulus for cultured smooth muscle cells (SMC), could contribute to proliferation after angioplasty.

METHODS

SMC were cultivated from human aorta and restenosed coronary lesions as well as from minipig aorta and from normal and post angioplasty coronary artery segments (n = 6 per source). 3H-thymidine incorporation was used as a measure of proliferation.

RESULTS

3H-thymidine incorporation varied greatly after passage 7 in all cell lines, but was significantly higher in SMC from human coronary restenosed lesions compared to those from human aorta and minipig coronary post angioplasty segments in passage 2 (44 +/- 6.4 x 10(3) cpm/5000 SMC vs 20 +/- 3.9 and 12.1 +/- 2.1). However, all SMC exhibited a dramatic increase of 3H-incorporation after passage 7. Growth factors stimulated 3H-thymidine incorporation either dose dependently (PDGF-BB and bFGF) or only very modestly (PDGF-AA, EGF, IGF-1). The most potent stimulation was seen with PDGF-BB, 50 ng/ml, and was 17 +/- 6% (human restenosed) and 16 +/- 8% (minipig post angioplasty) of the values observed after stimulation with 10% fetal calf serum. The most effective combination of growth factors, PDGF-BB (50 ng/ml) + bFGF(20 ng/ml) + IGF-1 (50 ng/ml), produced a 3H-thymidine incorporation of 44 +/- 10% (human restenosed) and 42 +/- 11% (minipig post angioplasty) of FCS values. Stimulation by isolated platelets was dose dependent and significantly higher: 75 +/- 19% and 70 +/- 15% of FCS values for those SMC.

CONCLUSIONS

SMC from all sources studied exhibit significant changes of proliferation with increasing passages, excluding the comparability of data obtained with cells in different passages. 2) Data obtained with SMC from any source might not apply for SMC from human coronary restenosed lesions. 3) Currently tested growth factors do not fully account for the proliferative effect of platelets on cultured SMC.

摘要

目的

血小板在血管成形术部位聚集，已证明其对培养的平滑肌细胞（SMC）是一种强大的增殖刺激因素，可能促使血管成形术后细胞增殖。

方法

从人主动脉、再狭窄的冠状动脉病变、小型猪主动脉以及正常和血管成形术后的冠状动脉节段（每个来源6例）培养SMC。采用3H-胸腺嘧啶核苷掺入法作为增殖的衡量指标。

结果

所有细胞系在第7代传代后，3H-胸腺嘧啶核苷掺入量差异很大，但与第2代人主动脉和小型猪冠状动脉血管成形术后节段的SMC相比，人冠状动脉再狭窄病变的SMC中该掺入量显著更高（44±6.4×10(3) cpm/5000 SMC对20±3.9和12.1±2.1）。然而，所有SMC在第7代传代后3H掺入量均显著增加。生长因子对3H-胸腺嘧啶核苷掺入的刺激呈剂量依赖性（PDGF-BB和bFGF）或仅非常轻微（PDGF-AA、EGF、IGF-1）。用50 ng/ml的PDGF-BB刺激效果最强，其掺入量为用10%胎牛血清刺激后所观察值的17±6%（人再狭窄病变）和16±8%（小型猪血管成形术后）。生长因子的最有效组合，即PDGF-BB（50 ng/ml）+bFGF（20 ng/ml）+IGF-1（50 ng/ml），使3H-胸腺嘧啶核苷掺入量达到胎牛血清值的44±10%（人再狭窄病变）和42±11%（小型猪血管成形术后）。分离的血小板刺激呈剂量依赖性且显著更高：这些SMC的掺入量为胎牛血清值的75±19%和70±15%。