Tulis D A, Prewitt R L
Department of Physiology, Eastern Virginia Medical School, Norfolk, Va., 23501-1980 USA.
J Vasc Res. 1998 Nov-Dec;35(6):413-20. doi: 10.1159/000025612.
Previous work from this laboratory demonstrated that in vivo exposure to elevated arterial flow stimulates endothelial and smooth muscle cell hyperplasia concomitant with lumen enlargement, medial wall hypertrophy, and increases in medial extracellular connective tissue in rat mesenteric small arteries. In an effort to elucidate the role of growth factors in mediating this arterial remodeling response, in situ hybridization was performed on control and high flow arterial sections using 35S-labeled riboprobes for PDGF-A, PDGF-B, basic FGF, and TGFbeta1 mRNA. Results demonstrate that after exposure to elevated arterial flow for 24 h, expression of PDGF-A mRNA in the media was significantly elevated over basal levels (+215%, p < 0.001). This expression decreased towards control levels by 3 and 7 days. Increased endothelial expression of PDGF-A mRNA over basal levels was evident after 3 and 7 days of elevated flow (+129%, p < 0.01; +182%; p < 0.01, respectively). Acute medial PDGF-A mRNA expression may result from elevated circumferential hoop stress secondary to flow-induced dilation while delayed expression in the endothelium may result from normalization of wall shear stress. Endothelial expression of PDGF-B mRNA was significantly elevated over control levels (+62%, p < 0.01) after exposure to high flow for 7 days. Expression of bFGF and TGFbeta1 mRNA was not significantly different between control and high flow vessels at all times measured. These results suggest a role for PDGF-A in regulating acute arterial remodeling following in vivo exposure to elevated flow.
该实验室之前的研究表明，在体内，大鼠肠系膜小动脉暴露于升高的动脉血流中会刺激内皮细胞和平滑肌细胞增生，同时伴有管腔扩大、中膜壁肥厚以及中膜细胞外结缔组织增加。为了阐明生长因子在介导这种动脉重塑反应中的作用，使用针对血小板衍生生长因子A（PDGF-A）、血小板衍生生长因子B（PDGF-B）、碱性成纤维细胞生长因子（bFGF）和转化生长因子β1（TGFβ1）mRNA的35S标记核糖探针，对对照和高血流动脉切片进行了原位杂交。结果表明，暴露于升高的动脉血流24小时后，中膜中PDGF-A mRNA的表达比基础水平显著升高（+215%，p<0.001）。这种表达在3天和7天时降至对照水平。在血流升高3天和7天后，内皮细胞中PDGF-A mRNA表达相对于基础水平明显增加（分别为+129%，p<0.01；+182%，p<0.01）。中膜急性PDGF-A mRNA表达可能是由于血流诱导的扩张导致周向环向应力升高所致，而内皮细胞中的延迟表达可能是由于壁面剪切应力恢复正常所致。暴露于高血流7天后，内皮细胞中PDGF-B mRNA的表达比对照水平显著升高（+62%，p<0.01）。在所有测量时间点，对照血管和高血流血管之间bFGF和TGFβ1 mRNA的表达均无显著差异。这些结果表明，PDGF-A在体内暴露于升高血流后调节急性动脉重塑中发挥作用。
