Nabel E G, Yang Z, Liptay S, San H, Gordon D, Haudenschild C C, Nabel G J
Department of Internal Medicine, Howard Hughes Medical Institute, University of Michigan, Ann Arbor 48109.
J Clin Invest. 1993 Apr;91(4):1822-9. doi: 10.1172/JCI116394.
Platelet-derived growth factor (PDGF) B chain induces cell proliferation in vitro and is associated with arterial lesions that cause cardiovascular disease. However, it has been difficult to document the biological response to PDGF B gene expression in arteries in vivo. To determine the biologic effects of this growth factor in vivo, we have introduced an eukaryotic expression vector plasmid encoding recombinant PDGF B by direct gene transfer into porcine iliofemoral arteries using DNA liposome complexes. The presence of PDGF B plasmid DNA and expression of recombinant mRNA were confirmed by polymerase chain reaction analysis, and recombinant PDGF protein was demonstrated by immunohistochemistry. Intimal thickening was observed in porcine arteries 21 days following transfection with the recombinant PDGF B gene compared with arteries transduced with a control gene, E. coli beta-galactosidase. An eightfold increase in intimal to medial ratio was present in PDGF B gene transfected arteries compared with control transfected arteries (P = 0.001). This study suggests that expression of a recombinant PDGF B gene in vivo can play a role in the induction of intimal hyperplasia, which can lead to cardiovascular diseases.
血小板衍生生长因子(PDGF)B链在体外可诱导细胞增殖,且与引发心血管疾病的动脉病变相关。然而,在体内动脉中记录对PDGF B基因表达的生物学反应一直很困难。为了确定这种生长因子在体内的生物学效应,我们使用DNA脂质体复合物通过直接基因转移将编码重组PDGF B的真核表达载体质粒导入猪的髂股动脉。通过聚合酶链反应分析证实了PDGF B质粒DNA的存在和重组mRNA的表达,并通过免疫组织化学证明了重组PDGF蛋白的存在。与用对照基因大肠杆菌β-半乳糖苷酶转导的动脉相比,用重组PDGF B基因转染的猪动脉在21天后观察到内膜增厚。与对照转染的动脉相比,PDGF B基因转染的动脉内膜与中膜比值增加了八倍(P = 0.001)。这项研究表明,体内重组PDGF B基因的表达可在诱导内膜增生中起作用,而内膜增生可导致心血管疾病。