Expression of Kunitz protease inhibitor--containing forms of amyloid beta-protein precursor within vascular thrombi.

Expression of Kunitz protease inhibitor--containing forms of amyloid beta-protein precursor within vascular thrombi.
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库尼茨蛋白酶抑制剂的表达——含有淀粉样β-蛋白前体形式在血管血栓内的表达。

DOI:
10.1161/01.cir.94.11.2728
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发表时间:
1996
期刊:
影响因子:
37.8
通讯作者:
Schleef,RR
Schleef,RR
中科院分区:
医学1区
文献类型:
--
作者:
Lang,IM;Moser,KM;Schleef,RR

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背景慢性血栓栓塞性肺动脉高压血管闭塞内新生血管的存在提示存在调节凝血系统的局部机制。本研究探讨了一种有效的抑制因子IXa和因子XIa(即,蛋白酶连接蛋白-2/淀粉样β蛋白前体,AβPP)的表达在有组织的血管闭塞收获从患者患有这种diseases.Methods和ResultsImmunohistochemistry分析显示,强烈的免疫反应性AβPP的单层细胞,线的新生血管。用35 S-UTP标记的反义核糖核酸探针进行原位杂交分析也检测到阳性信号,该探针识别该分子的各种可变剪接的mRNA形式。为了鉴定血栓内产生的AβPP的形式,从血栓中提取总RNA,进行逆转录,并使用聚合酶链反应(PCR)和位于编码选择性剪接的56个氨基酸Kunitz型蛋白酶抑制剂(KPI)结构域侧翼的引物进行扩增。主要PCR产物由255 bp和312 bp组成,对应于编码该结构域的转录本(即Aβ PP 751和Aβ PP 770)。原位杂交分析与使用35 S-UTP标记的反义核糖核酸探针互补的区域编码的KPI结构域证实了这些mRNA的存在下,在有核细胞内衬neovasculars.ConclusionsThe表达的AβPP在血栓内皮细胞的KPI亚型可能是一种机制,利用在这种疾病中,以改变局部止血平衡,保持区域血管通畅。
BackgroundThe presence of patent neovessels within vascular occlusions in chronic thromboembolic pulmonary hypertension suggests that local mechanisms exist to regulate the coagulation system. This study investigated the expression of a potent inhibitor of Factor IXa and Factor XIa (ie, protease nexin-2/amyloid β-protein precursor, AβPP) in the organized vascular occlusions harvested from patients with this disease.Methods and ResultsImmunohistochemical analysis revealed intense immunoreactivity for AβPP in the single layer of cells that line the neovessels. A positive signal was also detected by in situ hybridization analysis with the use of a35S-UTP–labeled antisense riboprobe that recognizes the various alternatively spliced mRNA forms of this molecule. To identify the forms of AβPP produced within the thrombi, total RNA was extracted from the thrombi, reverse transcribed, and subjected to amplification with the use of the polymerase chain reaction (PCR) and primers that flank the region encoding the alternatively spliced 56–amino acid Kunitz-type protease inhibitor (KPI) domain. The major PCR products consisted of 255 bp and 312 bp and corresponded to transcripts encoding this domain (ie, AβPP751and AβPP770). In situ hybridization analysis with the use of a35S-UTP–labeled antisense riboprobe complementary to the region encoding the KPI domain confirmed the presence of these mRNA species in nucleated cells lining the neovessels.ConclusionsThe expression of KPI-containing isoforms of AβPP in thrombus endothelial cells may represent one mechanism utilized in this disease to shift the local hemostatic balance and preserve regional vessel patency.
DOI: --
发表时间: 1994-09
期刊: The Journal of biological chemistry
影响因子: --
作者:
J. Davis-Salinas;S. Saporito-irwin;F. M. Donovan;Dennis Cunningham;W. E. Nostrand
通讯作者: J. Davis-Salinas;S. Saporito-irwin;F. M. Donovan;Dennis Cunningham;W. E. Nostrand
DOI: 10.1016/s0021-9258(18)60636-2
发表时间: 1988-04
期刊: The Journal of biological chemistry
影响因子: --
作者:
Raymond R. SchleefSS;Michael P. BevilacqualI;Michael Sawdeys;M. Gimbrone;David;LoskutoffS
通讯作者: Raymond R. SchleefSS;Michael P. BevilacqualI;Michael Sawdeys;M. Gimbrone;David;LoskutoffS
DOI: 10.1172/jci118396
发表时间: 1996-01-01
影响因子: 15.9
作者:
Eitzman, DT;McCoy, RD;Simon, RH
通讯作者: Simon, RH
DOI: 10.1161/01.cir.81.6.1735
发表时间: 1990-06-01
期刊: CIRCULATION
影响因子: 37.8
作者:
MOSER, KM;AUGER, WR;FEDULLO, PF
通讯作者: FEDULLO, PF
慢性肺血栓栓塞引起的肺动脉高压。
DOI: 10.7326/0003-4819-108-3-425
发表时间: 1988
影响因子: 39.2
作者:
S. Rich;Sidney Levitsky;Bruce H. Brundage
通讯作者: Bruce H. Brundage