Janakidevi K, Tiruppathi C, Del Vecchio P J, Pinheiro J M, Malik A B
Department of Physiology, Albany Medical College of Union University, New York 12208.
Am J Physiol. 1995 Mar;268(3 Pt 1):L465-70. doi: 10.1152/ajplung.1995.268.3.L465.
We compared the proliferative rates of vascular smooth muscle cells (VSMC) from pulmonary arteries of pulmonary hypertensive fawn-hooded rats (FHR) with VSMC from normotensive Sprague-Dawley rats (SDR). VSMC from FHR grew at increased rates and reached higher densities at all serum concentrations studied (5-20%) than the VSMC from SDR. The VSMC from FHR also responded to epidermal growth factor (EGF) at low serum concentrations, as evidenced by significantly greater DNA synthetic rates, than the control VSMC. The increased growth in these cells could be due to increased number and/or affinity of EGF receptors because of the higher specific binding of 125I-EGF to the VSMC from FHR. The VSMC from FHR and SDR were equally sensitive to the antiproliferative effects of heparin, suggesting that the heparin-sensitive pathways are not altered in the VSMC from FHR. These results suggest that the development of pulmonary hypertension in FHR may be related to the higher proliferative capacity of the pulmonary VSMC, which may be coupled to increased activity of the EGF receptors on these cells.
我们比较了肺动脉高压的淡色带帽大鼠（FHR）肺动脉血管平滑肌细胞（VSMC）与正常血压的斯普拉格-道利大鼠（SDR）VSMC的增殖速率。在所有研究的血清浓度（5%-20%）下，FHR的VSMC生长速率加快，且达到的细胞密度高于SDR的VSMC。在低血清浓度下，FHR的VSMC也对表皮生长因子（EGF）有反应，DNA合成速率显著高于对照VSMC。这些细胞生长增加可能是由于EGF受体数量增加和/或亲和力增加，因为125I-EGF与FHR的VSMC特异性结合更高。FHR和SDR的VSMC对肝素的抗增殖作用同样敏感，表明FHR的VSMC中肝素敏感途径未改变。这些结果表明，FHR肺动脉高压的发生可能与肺VSMC较高的增殖能力有关，这可能与这些细胞上EGF受体活性增加有关。
