Schriever C, Schmidt A, Breithardt G, Buddecke E
Institute of Arteriosclerosis Research, University of Münster, Germany.
Atherosclerosis. 1996 May;122(2):255-63. doi: 10.1016/0021-9150(95)05760-9.
Insulin-like growth factor I and II (IGF-I and -II)--two 7.65- and 7.47-kDA polypeptides belonging to the somatomedine family--are regular constituents of human blood plasma. Both factors exert mitogenic activity on a variety of cell types including arterial smooth muscle cells. In the present study, the effect of IGF-I and -II on cultured bovine coronary smooth muscle cells (cSMC) was assessed. Human recombinant IGF-I and IGF-II added to cSMC cultured in a medium containing 10% fetal bovine serum (FBS) decreased the cell number and [3H]thymidine incorporation in a dose dependent fashion up to 40% and 43% compared to control cells (100%). At the same time, the expression of basic fibroblast growth factor (bFGF) increased from 60 pg/5 x 10(4) cells (control) to 75 (IGF-I) and 113 pg/5 x 10(4) cells (IGF-II). In parallel with enhanced bFGF expression, the bFGF receptor content per cell and the [35S]sulfate incorporation into extracellular and cell-associated proteoglycans also increased under the influence of IGF-I and -II. In contrast, with low serum concentration (0.1% FBS) the addition of IGF-I and -II to bovine cSMC cultures resulted in a slight increase in cell number, protein content and [3H]thymidine incorporation as described in previous studies. These results suggest that the mitogenic activity of IGF-I and -II towards coronary smooth muscle cells depends on culture conditions. In the presence of 10% fetal bovine serum that mimics in vivo conditions, IGF-I and -II did not necessarily act as mitogenic factors but inhibited the proliferation of cSMC in vitro possibly by modulating antagonizing the action of other growth factors. Irrespective of the inhibition of cell division, the cellular bFGF, the bFGF receptor and the bFGF activity-related proteoheparan sulfate were overexpressed under the influence of IGF.
胰岛素样生长因子I和II（IGF-I和-II）——两种属于生长调节素家族的7.65 kDa和7.47 kDa多肽——是人体血浆的正常成分。这两种因子对包括动脉平滑肌细胞在内的多种细胞类型都具有促有丝分裂活性。在本研究中，评估了IGF-I和-II对培养的牛冠状动脉平滑肌细胞（cSMC）的影响。将重组人IGF-I和IGF-II添加到在含有10%胎牛血清（FBS）的培养基中培养的cSMC中，与对照细胞（100%）相比，细胞数量和[3H]胸苷掺入量以剂量依赖性方式减少，分别高达40%和43%。同时，碱性成纤维细胞生长因子（bFGF）的表达从60 pg/5×10(4)个细胞（对照）增加到75（IGF-I）和113 pg/5×10(4)个细胞（IGF-II）。与bFGF表达增强同时，在IGF-I和-II的影响下，每个细胞的bFGF受体含量以及细胞外和细胞相关蛋白聚糖中[35S]硫酸盐的掺入量也增加。相反，在低血清浓度（0.1% FBS）下，如先前研究所述，向牛cSMC培养物中添加IGF-I和-II会导致细胞数量、蛋白质含量和[3H]胸苷掺入量略有增加。这些结果表明IGF-I和-II对冠状动脉平滑肌细胞的促有丝分裂活性取决于培养条件。在模拟体内条件的10%胎牛血清存在下，IGF-I和-II不一定作为促有丝分裂因子起作用，而是可能通过调节拮抗其他生长因子的作用来抑制体外cSMC的增殖。无论细胞分裂受到抑制，细胞内的bFGF、bFGF受体和与bFGF活性相关的蛋白硫酸乙酰肝素在IGF的影响下都会过度表达。
