Increased vascular endothelial growth factor expression in human hearts with microvascular fibrin.
Increased vascular endothelial growth factor expression in human hearts with microvascular fibrin.
复制标题
通过微血管纤维蛋白增加人心脏中血管内皮生长因子的表达。
DOI：
10.1006/jmcc.2000.1292
复制
发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Torry,DS
中科院分区：
文献类型：
--
作者：
Torry,RJ;Bai,L;Miller,SJ;Labarrere,CA;Nelson,D;Torry,DS
我们已经表明，微血管的变化，促进纤维蛋白沉积在人类心脏异体移植物不利影响临床结果。然而，一些同种异体移植物在纤维蛋白沉积后毛细血管表现出表型变化，这随后提供了显着的生存优势。这些毛细血管变化的机制尚不清楚。同样，尽管我们已经证明了心脏同种异体移植物中微血管纤维蛋白沉积与血管内皮生长因子（VEGF）免疫反应性之间存在显著的时间关系，但在这种情况下，VEGF基因表达的细胞来源和相对变化尚不清楚。使用免疫细胞化学技术，没有纤维蛋白沉积的活检组织缺乏可检测到的VEGF免疫反应性，而纤维蛋白沉积的活检组织在心肌细胞、间质和一些微血管中显示VEGF免疫反应性。通过原位杂交，没有微血管纤维蛋白沉积的活检显示微弱的VEGF杂交信号主要局限于心肌细胞。在纤维蛋白沉积的活检中，在心肌细胞中检测到强烈的VEGF杂交信号，动脉平滑肌细胞偶尔被标记，内皮细胞很少被标记。通过定量RT-PCR，有纤维蛋白沉积的活组织（n=5）相对表达的VEGF mRNA比没有纤维蛋白沉积的活组织（n=5 P=0.02）多≡3倍。纤维蛋白沉积组血清VEGF滴度（372.9±66.7 pg/ml n=18）高于无纤维蛋白沉积组（172.1±25.0 pg/ml n=16） （P=0.01）。总的来说，这些结果支持了一个假设，即移植的人心脏微血管纤维蛋白沉积后，肌细胞来源的VEGF产生增加，可能以旁分泌的方式促进毛细血管的激活和表型变化，从而为同种异体移植物提供生存优势。
We have shown that microvascular changes that promote fibrin deposition in human cardiac allografts adversely affect clinical outcome. However, some allografts exhibit phenotypic changes in capillaries following the deposition of fibrin, which subsequently provide a significant survival advantage. The mechanism(s) involved in these capillary changes is(are) unknown. Similarly, although we have shown a significant temporal relationship between microvascular fibrin deposition and vascular endothelial growth factor (VEGF) immunoreactivity in cardiac allografts, the cellular source and relative changes in VEGF gene expression under these conditions are not known. Using immunocytochemical techniques, biopsies devoid of fibrin deposition lacked detectable VEGF immunoreactivity, whereas biopsies with fibrin deposition showed VEGF immunoreactivity in cardiocytes, interstitium, and some microvessels. By in situ hybridization, biopsies without microvascular fibrin deposition showed faint VEGF hybridization signals confined primarily to cardiocytes. In biopsies with fibrin deposition, strong VEGF hybridization signals were detected in cardiocytes, arteriolar smooth muscle cells were occasionally labeled, and endothelial cells were rarely labeled. By quantitative RT-PCR, biopsies with fibrin deposition (n=5) relatively expressed ≡three-fold more VEGF mRNA than biopsies without fibrin deposition (n=5 P=0.02). Serum VEGF titers also were greater (P=0.01) in recipients with fibrin deposition (372.9±66.7 pg/ml n=18) compared to recipients without fibrin deposition (172.1±25.0 pg/ml n=16). Collectively, these results support the hypothesis that increased myocyte-derived VEGF production following microvascular fibrin deposition in transplanted human hearts may act in a paracrine manner to promote activational and phenotypic changes in capillaries that provide a survival advantage for the allografts.