高同型半胱氨酸诱导新蛋白Carom的表达在内皮细胞的作用
发布时间：2018-08-20 14:43
【摘要】：目的:高同型半胱氨酸血症(HHcy)是心血管疾病的独立危险因素(CVD)。我们实验团队先前证明,同型半胱氨酸(Hcy)抑制血管内皮细胞(EC)细胞增殖、迁移和损伤后修复,但Hcy诱导的EC损伤分子机制尚不清楚。在这项研究中,我们发现了一种新的F-BAR蛋白Carom,可介导的Hcy诱导的EC迁移和血管生成抑制。方法:1、实时荧光定量聚合酶链反应(RT-PCR)和蛋白免疫印迹实验(WB)检测人动脉内皮细胞(HAEC),24h 50μm DL-Hcy刺激后,Carom m RNA和蛋白在内皮细胞的表达。2、高通量液相质谱法检测CBS KO小鼠同型半胱氨酸(Hcy)水平。WB检测CBS KO小鼠主动脉Carom的表达,WB及流式细胞仪技术(FACS)检测肺组织内皮细胞中Carom的表达。3、高通量液相质谱法检测HAEC Hcy、S-腺蛋氨酸(SAM)和S-腺苷高半胱氨酸(SAH)水平,并计算SAM/SAH比例。用Actinnomyocin D及AZC处理内皮细胞,RT-PCR检测内皮细胞Carom。4、Adv-Carom病毒或Carom Sh-RNA病毒转染HAEC 72h,提取完整RNA,进行Carom相关的microarray及cytokine array。5、Adv-Carom病毒或Carom Sh-RNA病毒转染HAEC 72h,RT-PCR检测Carom及CXCL10 m RNA的表达水平。6、Hcy干预24h,Adv-Carom或Carom Sh-RNA病毒转染HAEC后72h,进行细胞划痕实验,观察Hcy和Carom对内皮细胞迁移功能的影响。同时加入CXCL10中和抗体,细胞划痕实验检测内皮细胞Carom和CXCLl0对细胞迁移功能的影响。7、Hcy干预细胞后,提取不同细胞成分的蛋白,WB鉴定Carom在细胞质,膜,细胞核及细胞骨架上表达变化。设计并合成Carom相关的NLS肽,内皮细胞同时给予Hcy和NLS肽处理后,WB检测Carom在染色质结合细胞核(CB)中的表达。内皮细胞Adv-Carom转染和NLS肽处理后,RT-PCR检测CXCLl0m RNA的表达。8、给予内皮细胞Hcy或Carom相关病毒转染后,体外进行血管再生实验,检测Hcy和Carom对内皮细胞血管再生的抑制作用。9、内皮细胞给予Hcy或Carom相关病毒转染后,分别给予两种细胞内吞抑制剂Mitmab和Chroquine,流式细胞仪检测Hcy和Carom对人血管生长因子受体2(VEGFR2)表达的影响。10、PIP array观察GST-Carom融合蛋白对磷酸肌醇的结合能力。用生物素标记膜蛋白,Hcy干预后观察细胞膜蛋白内吞的情况。11、内皮细胞过表达Carom,免疫共沉淀联合质谱筛选,Carom可能的相互作用蛋白。结果:1、RT-PCR发现Hcy可诱导HAEC Carom m RNA的表达,分别为对照组1.87倍(12h),2.72倍(24h)和2.45倍(48h)P0.05。同时DL-Hcy可诱导内皮细胞Carom蛋白表达增加,并呈时间依赖性,48h Carom蛋白表达最高为对照组的2.2倍(P0.05)。2、发现12-16周Tg-h CBS Cbs-/-小鼠血浆Hcy水平为50-100μm,Tg-h CBS Cbs+/-和Tg-h CBS Cbs+/+小鼠血浆Hcy水平小于10μm。血浆Hcy水平高的Tg-h CBS Cbs-/-小鼠主动脉及肺组织内皮细胞Carom的表达高于对照组小鼠,是对照组小鼠的1.4倍和1.6倍(P0.05)。3、Hcy干预可增加内皮细胞SAH水平约为对照组的1.8倍(P0.05),降低了内皮细胞SAM/SAH的比例由原来2.2降为0.5左右(P0.05),导致内皮细胞的低甲基化水平。Actinomyosin D可阻断Hcy诱导内皮细胞Carom m RNA的表达。不同浓度甲基化抑制剂AZC干预内皮细胞后,Carom蛋白的表达增加分别为对照组的1.9和2.2倍(P0.05)。4、Carom microarray筛选发现,与Adv-CT转染组相比,Adv-Carom转染组可使459个基因表达上调和460个基因表达下降(P0.05,FC1.2),Sh-RNA Carom可使653个基因表达下降,537个基金表达升高(P0.05,FC1.2)。其中有42个基因同时受Adv-Carom升高和sh-RNA Carom下降的调节。13个基因同时受Adv-Carom下降和sh-RANA Carom升高的调节。其中受Carom病毒转染变化最大的基因是CXCL10。5、DL-Hcy 50μm分别干预HAEC 12h、24h、48h小时,RT-PCR发现同型半胱氨酸增加内皮细胞Carom m RNA表达的同时,也增加CXCL10 m RNA的表达,并且在24h表达最高,升高为对照组22.1倍(P0.05)。用内皮细胞过表达Carom后发现,Adv-Carom不仅能升高Carom m RNA的表达,同时CXCL10 m RNA也升高为对照组的27.5倍(P0.05)。Carom Sh-RNA转染后,可抑制同型半胱氨酸诱导Carom的表达0.32倍(P0.05),同时抑制Hcy诱导CXCL10 m RNA的表达1.1倍(P0.05)。6、细胞划痕实验发现,Hcy刺激或Adv Carom病毒转染可抑制内皮细胞的迁移,Carom sh-RNA可改善Hcy对内皮细胞迁移的抑制作用(P0.05),CXCLl0中和抗体(a-CXCL10)可减轻Carom对内皮细胞迁移的抑制作用(P0.05)。7、WB结果发现Carom除了在细胞膜(ME)表达最多外,Carom还可以在细胞质(CE),可溶性细胞核(NE),染色质结合细胞核(CB)和细胞骨架(PE)中表达。同型半胱氨酸干预内皮细胞(HAEC)24h,Carom蛋白主要在CB和PE中表达增加,分别为对照组2.2倍和1.75倍(P0.05)。Carom NLS肽可减少同型半胱氨酸诱导Carom在染色质结合细胞核(CB)中的表达,同时可抑制Carom诱导的CXCLl0 m RNA的表达,提示Carom调节CXCLl0的表达可能与细胞核内Carom的表达和Carom的入核运动相关。8、内皮细胞小管形成实验发现,内皮细胞降低Carom表达后,可改善同型半胱氨酸对内皮细胞血管生成的抑制作用,由原来的35%升高为80%(P0.05),新生血管数量由原来的20上升至42(P0.05);内皮细胞过表达Carom可明显抑制内皮细胞血管再生过程(P0.05)。Carom对内皮细胞的增值作用无影响。9、流式细胞仪检测发现,与Adv-CT相比,过表达Carom组内皮细胞膜VEGFR2明显减少为28.6%(P0.05),同型半胱氨酸也可抑制VEGFR2在内皮细胞的表达为41%(P0.05),同时给予Sh-RNA Carom病毒转染后VEGFR2的表达升高为49%(P0.05,无统计学意义)。内吞抑制剂Mitmab可改善同型半胱氨酸和Adv-Carom对内皮细胞膜VEGFR2表达的抑制,分别由原来39%升高至58%,39%升高至51%(P0.05),Chroquine对VEGFR2表达无影响。10、PIP array表明GST-Carom融合蛋白易与各种磷酸肌醇结合,对Ptdlns(3)P及Ptdlns(3,5)P亲和力最大。细胞膜蛋白生物素标记细胞内吞实验表明,Hcy可诱导内皮细胞Carom及VEGFR2的内吞作用。11、免疫共沉淀蛋白印迹实验(Co-IP)发现在Hcy刺激下,Carom不能与VEGFR2,CASK和MAGI1连接发生相互作用。过表达Carom免疫共沉淀联合蛋白质谱分析发现,Carom可能在内皮细胞有13个相互作用蛋白,其中TRIM21可能通过与Carom连接,参与和介导Carom在内皮细胞的内吞。结论:1、Carom可在Hcy诱导的内皮细胞和高Hcy血症的小鼠肺内皮细胞和主动脉中高表达,其机制可能与内皮细胞低甲基化水平相关。2、过表达Carom可增加CXCLl0 m RNA的表达,Carom可能通过CXCLl0介导Hcy对内皮细胞迁移功能的抑制,其机制可能与Carom NLS介导的染色质结合细胞核(CB)Carom的表达增加及Carom的入核运动相关。3、Carom可介导Hcy对内皮细胞血管生成的抑制,抑制内皮细胞膜VEGFR2的表达,其机制可能与Carom介导的细胞内吞作用相关。
[Abstract]:AIM: Hyperhomocysteinemia (HHcy) is an independent risk factor for cardiovascular disease (CVD). Our team has previously demonstrated that homocysteine inhibits the proliferation, migration and repair of vascular endothelial cells (EC) cells, but the molecular mechanism of Hcy-induced EC injury remains unclear. F-BAR protein Carom can mediate Hcy-induced EC migration and angiogenesis inhibition. Methods: 1. Real-time fluorescence quantitative polymerase chain reaction (RT-PCR) and protein immunoblotting assay (WB) were used to detect the expression of Carom m RNA and protein in human arterial endothelial cells (HAEC), 24 h 50 micron DL-Hcy stimulation, and high-throughput liquid chromatography-mass spectrometry was used to detect CBS KO. The levels of homocysteine (Hcy) in mice were measured by WB. The expression of Carom in the aorta of CBS KO mice was detected by WB. The expression of Carom in lung endothelial cells was detected by WB and FACS. The levels of HAEC Hcy, S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) were detected by high-throughput liquid chromatography-mass spectrometry. The ratio of SAM to SAH was calculated by Actinnomyocin D and FACS. Endothelial cells were treated with AZC. Carom 4, Adv-Carom virus or Carom Sh-RNA virus were transfected into HAEC by RT-PCR for 72 hours. Complete RNA was extracted and transfected with Carom-related microarray and cytokine array. 72 hours after transfection of HAEC with rom-Sh-RNA virus, the effects of Hcy and Carom on the migration of endothelial cells were observed. At the same time, CXCL-10 neutralizing antibody was added. The effects of Carom and CXCLl-0 on the migration of endothelial cells were detected by cell scratch test. 7. After Hcy interfered with cells, the proteins of different cell components were extracted and the Carom was identified by WB. Carom-related NLS peptides were designed and synthesized. After endothelial cells were treated with Hcy and NLS peptides, the expression of Carom in chromatin-binding nucleus (CB) was detected by WB. After endothelial cells were transfected with Adv-Carom and NLS peptides, the expression of CXCLl0m RNA was detected by RT-PCR. Hcy or Caro peptides were given to endothelial cells. Vascular regeneration test was carried out in vitro after transfection of m-associated virus to detect the inhibitory effect of Hcy and Carom on vascular regeneration of endothelial cells. 9. After transfection of Hcy or Carom-related virus, endothelial cells were given two kinds of endocytosis inhibitors Mitmab and Chroquine respectively. The expression of human vascular growth factor receptor 2 (VEGFR2) was detected by flow cytometry. PIP array was used to observe the binding ability of GST-Carom fusion protein to inositol phosphate.Biotin-labeled membrane protein was used to observe the endocytosis of membrane protein after Hcy intervention.11.Overexpression of Carom in endothelial cells was observed.Immunocoprecipitation combined with mass spectrometry was used to screen the possible interaction protein of Carom.Results:1.RT-PCR showed that Hcy could induce HAEC Caro. The expression of M RNA was 1.87 times (12h), 2.72 times (24h) and 2.45 times (48h) of the control group, respectively, P 0.05. DL-Hcy could induce the expression of Carom protein in endothelial cells in a time-dependent manner. The highest expression of Carom protein was 2.2 times (P 0.05). It was found that the plasma Hcy level of Tg-h CBS Cbs-/-mice at 12-16 weeks was 50-100um, Tg-h CBS Cbs+/-and Tg-h CBS Cbs-/-2, respectively. The levels of plasma Hcy in Tg-h CBS Cbs+/+ mice were less than 10 microns. The expression of Carom in endothelial cells of aorta and lung tissue of Tg-h CBS Cbs-/- mice with high plasma Hcy level was 1.4 and 1.6 times higher than that of control mice (P 0.05). Hcy intervention could increase the level of SAH in endothelial cells by 1.8 times (P 0.05), and decrease the level of SAH in endothelial cells. Actinomyosin D blocked Hcy-induced expression of Carom m RNA in endothelial cells. The expression of Carom protein increased by 1.9 and 2.2 times (P 0.05). Carom microarray sieve and AZC at different concentrations increased the expression of Carom protein in endothelial cells, respectively. Compared with the Adv-CT transfection group, the Adv-Carom transfection group could up-regulate the expression of 459 genes and down-regulate the expression of 460 genes (P 0.05, FC1.2), Sh-RNA Carom could down-regulate the expression of 653 genes and up-regulate the expression of 537 funds (P 0.05, FC1.2). Among them, CXCL10.5 was the most variable gene transfected by Carom virus, and DL-Hcy 50 micron interfered with HAEC 12 h, 24 h and 48 h respectively. RT-PCR showed that homocysteine increased the expression of Carom RNA and CXCL10 m RNA in endothelial cells, and the expression was the highest at 24 h, up to 0. Overexpression of Carom in endothelial cells showed that Adv-Carom not only increased the expression of Carom m RNA, but also increased the expression of CXCL10 m RNA by 27.5 times (P 0.05). Carom Sh-RNA transfection inhibited homocysteine-induced expression of Carom by 0.32 times (P 0.05) and inhibited Hcy-induced expression of CXCL10 m RNA by 1.1 times (P 0.0). 5) 6. Cell scratch test showed that Hcy stimulation or Adv Carom virus transfection could inhibit endothelial cell migration, Carom sh-RNA could improve the inhibition of Hcy on endothelial cell migration (P 0.05), CXCLl0 neutralizing antibody (a-CXCL10) could reduce the inhibition of Carom on endothelial cell migration (P 0.05). 7. WB results showed that Carom was expressed in the cell membrane (ME) except for Hcy. At most, Carom could also be expressed in cytoplasm (CE), soluble nucleus (NE), chromatin-binding nucleus (CB) and cytoskeleton (PE). Homocysteine interfered with endothelial cells (HAEC) for 24 hours, and the expression of Carom protein increased mainly in CB and PE, which were 2.2 and 1.75 times higher than that in control group (P 0.05). Carom NLS peptide decreased the induction of Ca by homocysteine. The expression of ROM in chromatin-binding cell nucleus (CB) and the expression of CXCLl0 m RNA induced by Carom were inhibited, suggesting that the expression of CXCLl0 regulated by Carom may be related to the expression of Carom in the nucleus and the movement of Carom into the nucleus. 8. Tubular formation experiment of endothelial cells showed that endothelial cells could improve homocysteine pairs by reducing the expression of Carom. The inhibition of endothelial cell angiogenesis increased from 35% to 80% (P 0.05), and the number of neovascularization increased from 20% to 42 (P 0.05). Overexpression of Carom in endothelial cells significantly inhibited the process of endothelial cell angiogenesis (P 0.05). Carom had no effect on endothelial cell proliferation. The expression of vascular endothelial growth factor R2 was significantly decreased by 28.6% (P Inhibition of the expression of VEGF R2 on the cell membrane increased from 39% to 58% and 39% to 51% (P 0.05), respectively. Chroquine had no effect on the expression of VEGF R2. 10. PIP array showed that GST-Carom fusion protein was easy to bind to various inositol phosphate and had the highest affinity for Ptdlns (3) P and Ptdlns (3,5) P. Carom could not interact with the binding of VEGFR2, CASK and MAGI1 under the stimulation of Hcy. Overexpression of Carom immunoprecipitation combined with protein profiling revealed that Carom may have 13 interacting proteins in endothelial cells, including TRIM21. Conclusion: 1. Carom can be highly expressed in Hcy-induced endothelial cells and in the pulmonary endothelial cells and aortas of mice with hypercythemia. The mechanism may be related to the hypomethylation level of endothelial cells. 2. Overexpression of Carom can increase the expression of CXCLl0 m RNA. Carom may increase the expression of CXCLl0 m RNA through CXCLl0. The mechanism of Hcy-mediated inhibition of endothelial cell migration may be related to the increased expression of Carom in the chromatin-binding nucleus (CB) mediated by Carom NLS and the movement of Carom into the nucleus. 3. Carom can mediate the inhibition of Hcy on endothelial cell angiogenesis and inhibit the expression of VEGF R2 in endothelial cell membrane. The mechanism may be Carom-mediated endocytosis. Function related.
【学位授予单位】：南昌大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R54
[Abstract]:AIM: Hyperhomocysteinemia (HHcy) is an independent risk factor for cardiovascular disease (CVD). Our team has previously demonstrated that homocysteine inhibits the proliferation, migration and repair of vascular endothelial cells (EC) cells, but the molecular mechanism of Hcy-induced EC injury remains unclear. F-BAR protein Carom can mediate Hcy-induced EC migration and angiogenesis inhibition. Methods: 1. Real-time fluorescence quantitative polymerase chain reaction (RT-PCR) and protein immunoblotting assay (WB) were used to detect the expression of Carom m RNA and protein in human arterial endothelial cells (HAEC), 24 h 50 micron DL-Hcy stimulation, and high-throughput liquid chromatography-mass spectrometry was used to detect CBS KO. The levels of homocysteine (Hcy) in mice were measured by WB. The expression of Carom in the aorta of CBS KO mice was detected by WB. The expression of Carom in lung endothelial cells was detected by WB and FACS. The levels of HAEC Hcy, S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) were detected by high-throughput liquid chromatography-mass spectrometry. The ratio of SAM to SAH was calculated by Actinnomyocin D and FACS. Endothelial cells were treated with AZC. Carom 4, Adv-Carom virus or Carom Sh-RNA virus were transfected into HAEC by RT-PCR for 72 hours. Complete RNA was extracted and transfected with Carom-related microarray and cytokine array. 72 hours after transfection of HAEC with rom-Sh-RNA virus, the effects of Hcy and Carom on the migration of endothelial cells were observed. At the same time, CXCL-10 neutralizing antibody was added. The effects of Carom and CXCLl-0 on the migration of endothelial cells were detected by cell scratch test. 7. After Hcy interfered with cells, the proteins of different cell components were extracted and the Carom was identified by WB. Carom-related NLS peptides were designed and synthesized. After endothelial cells were treated with Hcy and NLS peptides, the expression of Carom in chromatin-binding nucleus (CB) was detected by WB. After endothelial cells were transfected with Adv-Carom and NLS peptides, the expression of CXCLl0m RNA was detected by RT-PCR. Hcy or Caro peptides were given to endothelial cells. Vascular regeneration test was carried out in vitro after transfection of m-associated virus to detect the inhibitory effect of Hcy and Carom on vascular regeneration of endothelial cells. 9. After transfection of Hcy or Carom-related virus, endothelial cells were given two kinds of endocytosis inhibitors Mitmab and Chroquine respectively. The expression of human vascular growth factor receptor 2 (VEGFR2) was detected by flow cytometry. PIP array was used to observe the binding ability of GST-Carom fusion protein to inositol phosphate.Biotin-labeled membrane protein was used to observe the endocytosis of membrane protein after Hcy intervention.11.Overexpression of Carom in endothelial cells was observed.Immunocoprecipitation combined with mass spectrometry was used to screen the possible interaction protein of Carom.Results:1.RT-PCR showed that Hcy could induce HAEC Caro. The expression of M RNA was 1.87 times (12h), 2.72 times (24h) and 2.45 times (48h) of the control group, respectively, P 0.05. DL-Hcy could induce the expression of Carom protein in endothelial cells in a time-dependent manner. The highest expression of Carom protein was 2.2 times (P 0.05). It was found that the plasma Hcy level of Tg-h CBS Cbs-/-mice at 12-16 weeks was 50-100um, Tg-h CBS Cbs+/-and Tg-h CBS Cbs-/-2, respectively. The levels of plasma Hcy in Tg-h CBS Cbs+/+ mice were less than 10 microns. The expression of Carom in endothelial cells of aorta and lung tissue of Tg-h CBS Cbs-/- mice with high plasma Hcy level was 1.4 and 1.6 times higher than that of control mice (P 0.05). Hcy intervention could increase the level of SAH in endothelial cells by 1.8 times (P 0.05), and decrease the level of SAH in endothelial cells. Actinomyosin D blocked Hcy-induced expression of Carom m RNA in endothelial cells. The expression of Carom protein increased by 1.9 and 2.2 times (P 0.05). Carom microarray sieve and AZC at different concentrations increased the expression of Carom protein in endothelial cells, respectively. Compared with the Adv-CT transfection group, the Adv-Carom transfection group could up-regulate the expression of 459 genes and down-regulate the expression of 460 genes (P 0.05, FC1.2), Sh-RNA Carom could down-regulate the expression of 653 genes and up-regulate the expression of 537 funds (P 0.05, FC1.2). Among them, CXCL10.5 was the most variable gene transfected by Carom virus, and DL-Hcy 50 micron interfered with HAEC 12 h, 24 h and 48 h respectively. RT-PCR showed that homocysteine increased the expression of Carom RNA and CXCL10 m RNA in endothelial cells, and the expression was the highest at 24 h, up to 0. Overexpression of Carom in endothelial cells showed that Adv-Carom not only increased the expression of Carom m RNA, but also increased the expression of CXCL10 m RNA by 27.5 times (P 0.05). Carom Sh-RNA transfection inhibited homocysteine-induced expression of Carom by 0.32 times (P 0.05) and inhibited Hcy-induced expression of CXCL10 m RNA by 1.1 times (P 0.0). 5) 6. Cell scratch test showed that Hcy stimulation or Adv Carom virus transfection could inhibit endothelial cell migration, Carom sh-RNA could improve the inhibition of Hcy on endothelial cell migration (P 0.05), CXCLl0 neutralizing antibody (a-CXCL10) could reduce the inhibition of Carom on endothelial cell migration (P 0.05). 7. WB results showed that Carom was expressed in the cell membrane (ME) except for Hcy. At most, Carom could also be expressed in cytoplasm (CE), soluble nucleus (NE), chromatin-binding nucleus (CB) and cytoskeleton (PE). Homocysteine interfered with endothelial cells (HAEC) for 24 hours, and the expression of Carom protein increased mainly in CB and PE, which were 2.2 and 1.75 times higher than that in control group (P 0.05). Carom NLS peptide decreased the induction of Ca by homocysteine. The expression of ROM in chromatin-binding cell nucleus (CB) and the expression of CXCLl0 m RNA induced by Carom were inhibited, suggesting that the expression of CXCLl0 regulated by Carom may be related to the expression of Carom in the nucleus and the movement of Carom into the nucleus. 8. Tubular formation experiment of endothelial cells showed that endothelial cells could improve homocysteine pairs by reducing the expression of Carom. The inhibition of endothelial cell angiogenesis increased from 35% to 80% (P 0.05), and the number of neovascularization increased from 20% to 42 (P 0.05). Overexpression of Carom in endothelial cells significantly inhibited the process of endothelial cell angiogenesis (P 0.05). Carom had no effect on endothelial cell proliferation. The expression of vascular endothelial growth factor R2 was significantly decreased by 28.6% (P Inhibition of the expression of VEGF R2 on the cell membrane increased from 39% to 58% and 39% to 51% (P 0.05), respectively. Chroquine had no effect on the expression of VEGF R2. 10. PIP array showed that GST-Carom fusion protein was easy to bind to various inositol phosphate and had the highest affinity for Ptdlns (3) P and Ptdlns (3,5) P. Carom could not interact with the binding of VEGFR2, CASK and MAGI1 under the stimulation of Hcy. Overexpression of Carom immunoprecipitation combined with protein profiling revealed that Carom may have 13 interacting proteins in endothelial cells, including TRIM21. Conclusion: 1. Carom can be highly expressed in Hcy-induced endothelial cells and in the pulmonary endothelial cells and aortas of mice with hypercythemia. The mechanism may be related to the hypomethylation level of endothelial cells. 2. Overexpression of Carom can increase the expression of CXCLl0 m RNA. Carom may increase the expression of CXCLl0 m RNA through CXCLl0. The mechanism of Hcy-mediated inhibition of endothelial cell migration may be related to the increased expression of Carom in the chromatin-binding nucleus (CB) mediated by Carom NLS and the movement of Carom into the nucleus. 3. Carom can mediate the inhibition of Hcy on endothelial cell angiogenesis and inhibit the expression of VEGF R2 in endothelial cell membrane. The mechanism may be Carom-mediated endocytosis. Function related.
【学位授予单位】：南昌大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R54
【相似文献】
相关期刊论文 前10条
1 刘欣,石应康,祝彼得;培养内皮细胞的分化[J];生物医学工程学杂志;1999年02期
2 卫朝霞,刘永波;一种新的内皮细胞分离方法[J];河南职工医学院学报;2003年03期
3 任德成;胡娟娟;张均田;杜冠华;;血管内皮细胞损伤机制研究[J];医学研究通讯;2003年10期
4 潘虹;王庭槐;;内皮细胞caveolae,caveolin-1的生理功能[J];医学综述;2006年22期
5 殷观梅;;血管内皮细胞生长抑制因子研究进展[J];河北医药;2008年12期
6 刘宝宜,陈铁镇,张宝庚,宋继业;动脉粥样硬化形成过程中内皮细胞病变的研究(摘要)——主动脉内皮细胞平掙,扫描电镜及透射电镜的观察[J];中国医科大学学报;1981年S1期
7 刘宝宜,陈铁镇,张宝庚,宋继业;动脉粥样硬化形成过程中内皮细胞的形态学变化的研究(主动脉内皮细胞平铺技术,扫描电镜及透射电镜的方法)[J];中国医科大学学报;1982年03期
8 张连元;;动脉粥样硬化发病机理中平滑肌和内皮细胞的机能[J];煤矿医学;1983年04期
9 刘怀琼;李德馨;;内皮细胞的功能与休克的关系[J];国外医学.麻醉学与复苏分册;1985年04期
10 何泽涌;;关于内皮细胞研究的某些进展[J];山西医药杂志;1987年03期
相关会议论文 前10条
1 应大君;陈卫军;周丁华;;内皮细胞机械感受功能的实验研究[A];面向21世纪的科技进步与社会经济发展（下册）[C];1999年
2 邓红;李懿萍;来茂德;;高糖环境细胞间相互作用对内皮细胞产生活性氧和血管内皮细胞生长因子的影响[A];中华医学会病理学分会2005年学术年会论文汇编[C];2005年
3 林萍章;PualJ.Pearson;RaymondCartier;KazuhiroHashimoto;HartzellV.Schaff;;内膜再生过程中,内皮细胞之反应[A];海峡两岸电子显微学讨论会论文专集[C];1991年
4 赵彭涛;李志超;董明清;贾斌;张莉莉;;LPS对培养的BPAECsⅠ型Na~+/H~+交换器活性的影响[A];第六次全国缺氧和呼吸病理生理学术会议论文摘要汇编[C];2003年
5 熊建琼;朱佩芳;王正国;蒋建新;;髓样分化蛋白-2在内毒素与内皮细胞结合中的作用[A];第十一次全国急诊医学学术会议暨中华医学会急诊医学分会成立二十周年庆典论文汇编[C];2006年
6 王心华;甄永苏;;烯二炔类抗生素力达霉素抑制内皮细胞生长和诱导内皮细胞凋亡[A];2000全国肿瘤学术大会论文集[C];2000年
7 李彦荣;应晨江;易海维;衣卫杰;孟依;刘烈刚;孙秀发;;绿茶多酚对牛内皮细胞窖蛋白-1表达的影响[A];湖北省、武汉市营养学会第十一届学术会议论文汇编[C];2007年
8 蔡绍皙;张莉;韩亚刚;蒋稼欢;;流动腔底面内皮细胞图型化研究与图像处理[A];第十次中国生物物理学术大会论文摘要集[C];2006年
9 汪毅;陈允钦;;高密度脂蛋白与内皮功能[A];第六次全国中西医结合心血管会学术会议论文汇编[C];2002年
10 马向红;黄体钢;杨万松;周丽娟;;四氢生物喋呤对内皮细胞产生一氧化氮和超氧阴离子的影响[A];中华医学会心血管病分会第八次全国心血管病学术会议汇编[C];2004年
相关重要报纸文章 前6条
1 ;中药抗血栓机理及对内皮细胞的生物医学研究取得佳绩[N];科技日报;2000年
2 赵军;耳毒性药物对耳蜗螺旋动脉平滑肌和内皮细胞电生理特性的影响项目[N];科技日报;2007年
3 华朋;热爱老年事业 投身老年医药[N];中国老年报;2000年
4 高国起;提升ACE2活性可消退动脉硬化斑块[N];中国医药报;2010年
5 佳愉;中药善调理 降压重保肾[N];中国中医药报;2009年
6 刘道安;保护动脉内膜 减少冠心病发生[N];中国医药报;2005年
相关博士学位论文 前10条
1 白云城;LPS调控静脉内皮细胞膜形态及通透性引发血栓形成的实验研究[D];昆明医科大学;2015年
2 宋恩;内皮细胞源性KLF15调控TM激活蛋白C抗凝血途径及MCP-1介导炎性反应影响DVT形成的实验研究[D];昆明医科大学;2015年
3 宋凯;口腔癌—内皮细胞融合的分子调控机制及潜在作用[D];武汉大学;2014年
4 薛珊珊;用代谢组学方法研究DNA甲基化对花生四烯酸代谢的影响及血管内皮激活的机制[D];天津医科大学;2015年
5 李强;Rho GTPases及其信号通路在1-磷酸鞘胺醇介导的内皮细胞功能变化中的作用[D];南方医科大学;2013年
6 陈学军;SUR2B/Kir6.1通道开放剂介导内皮细胞保护效应分子途径的研究[D];中国人民解放军军事医学科学院;2016年
7 王苏阳;埃他卡林对体循环、脑循环、肺循环微动脉内皮细胞SUR2B/Kir6.1通道的激活作用及能量代谢物质的调节作用[D];中国人民解放军军事医学科学院;2016年
8 苑t，
本文编号：2194006
本文链接：https://www.wllwen.com/yixuelunwen/xxg/2194006.html
最近更新
教材专著
