TNFα对血管内皮细胞PDGF-B链基因转录的影响

ＴＮＦα主要由巨噬细胞、Ｔ细胞和ＮＫ细胞产生,是一种在急、慢性炎症过程中均有重要作用的炎症介质。动脉粥样硬化（ＡＳ）是以动脉壁内皮结构、功能损害和平滑肌细胞增殖变化为主的慢性炎症过程。ＡＳ时ＴＮＦα合成增多,且与ＡＳ的严重程度成正比。ＰＤＧＦ是以二聚体（ＡＡ,ＢＢ和ＡＢ）形式存在的促分裂剂。其中,ＰＤＧＦ－Ｂ链由ＰＤＧＦ－Ｂ链基因编码,该基因ｍＲＮＡ在ＡＳ血管内皮细胞中表达明显增高。因此,研究在ＴＮＦα作用下,血管内皮细胞ＰＤＧＦ－Ｂ链基因表达调控的分子机制对于阐明动脉粥样硬化的发病机制具有重要…     

缺氧对肺动脉内皮细胞PDGF基因及PDGF—B链蛋白表面的影响

应用核酸杂交和定量免疫细胞化学分析技术研究了缺氧对猪肺动脉内皮细胞血小板源性生长因子ＰＤＧＦ基因及ＰＤＧＦ－Ｂ链蛋白表达的影响。结果，缺氧能明显增强肺动脉内皮ＰＤＧＦ－Ｂ细胞边ｍＲＮＡ的表达，而ＰＤＧＦ－Ａ链ｍＲＮＡ表达水平无明显改变。免疫细胞化学定量分析与证实ＰＤＧＦ－Ｂ链蛋白染色比正常对照明显增强，与ＰＤＧＦ－Ｂ链基因表达的改变基本一致。提示缺氧可以刺激肺动脉内皮细胞ＰＤＧＦ的表达。ＰＤＦＧ在     

缺氧对肺动脉内皮细胞PDGF基因及PDGF－B链蛋白表达的影响

应用核酸杂交和定量免疫细胞化学分析技术研究了缺氧对猪肺动脉内皮细胞血小板源性生长因子ＰＤＧＦ基因及ＰＤＧＦ－Ｂ链蛋白表达的影响。结果表明，缺氧能明显增强肺动脉内皮细胞ＰＤＧＦ＿Ｂ链ｍＲＮＡ的表达，而ＰＤＧＦ－Ａ链ｍＲＮＡ表达水平无明显改变。免疫细胞化学定量分析也证实ＰＤＧＦ－Ｂ链蛋白染色比正常对照明显增强，与ＰＤＧＦ－Ｂ链基因表达的改变基本一致。提示缺氧可以刺激肺动脉内皮细胞ＰＤＧＦ的表达。ＰＤＦＧ在缺氧引起的肺动脉高压血管构形改建中可能具有重要作用。     

缺氧促进猪肺动脉内皮细胞sis／PDGF—B链基因的表达

应用Ｎｏｒｔｈｅｒｎｂｌｏｔ和Ｓｌｏｔ－ｂｌｏｔ杂交技术研究了缺氧对猪肺动脉内皮细胞血小板源性生长因子（ＰＤＧＦ）基因表达的影响，结果表明，缺氧能明显中肺动脉内皮细胞ＰＤＧＦ－Ｂ链ｍＲＮＡ的表达，而ＰＤＧＦ－Ａ链ｍＲＮＡ表达无明显影响，提示缺氧可能是体内刺激肺动脉内皮细胞ｓｉｓ／ＰＤＧＦ－Ｂ链基因表达的因素之一，通过肺动脉平滑机细胞增生和收缩，在肺动脉高压血管改建中可能具有重要作用。     

5‘上游序列对TNFα诱导内皮细胞血小板源生长因子—B链基因…

目的和方法：为探讨人血小板源生长因子（ＰＤＧＦ）－Ｂ链基因５‘上游序列在ＴＮＦα诱导内皮细胞该基因转录中的调控作用,本研究将构建的一系列含人ＰＤＧＦ－Ｂ链基因不同上游序列荧光素酶报告基因质粒,与内参照质粒ｐＳＶ－β－Ｇａｌ共转染培养的人脐静脉内皮细胞,分别检测了不同浓度和不同持续时间ＴＮＦα作用下转染内皮细胞荧光素酶比活性,观察了５’上游序列的定向删切对ＴＮＦα诱导内皮细胞ＰＤＧＦ－Ｂ链基因转录的     

缺氧内皮细胞介导肺动脉平滑肌细胞血小板源性生长因子mRNA表达

目的探讨缺氧时肺动脉内皮细胞对肺动脉平滑肌细胞ＰＤＧＦ自分泌的影响。方法实验分３组：无血清培养组、常氧性内皮细胞条件培养液组及缺氧性内皮细胞条件培养液组。应用原位杂交和图像分析技术检测猪肺动脉平滑肌细胞ＰＤＧＦＡ和ＰＤＧＦＢ链ｍＲＮＡ表达。结果无血清培养的肺动脉平滑肌细胞有ＰＤＧＦＡ和ＰＤＧＦＢ链ｍＲＮＡ弱表达;内皮细胞条件培养液明显增加肺动脉平滑肌细胞ＰＤＧＦＡ和ＰＤＧＦＢ链ｍＲＮＡ表达,两者分别为无血清培养组的１．８倍和１．７倍（Ｐ＜０．０１）,为常氧内皮细胞条件培养液培养组的１．４倍和１．５倍（Ｐ＜０．０１）。结论缺氧时肺动脉内皮细胞可以介导肺动脉平滑肌细胞ＰＤＧＦ的自分泌,可能在缺氧性肺动脉高压血管构形改建中具有重要作用     

缺氧促进猪肺动脉内皮细胞sis／PDGF－B链基因的表达

应用Ｎｏｒｔｈｅｒｎｂｌｏｔ和Ｓｌｏｔ一ｂｌｏｔ杂交技术研究了缺氧对猪肺动脉内皮细胞血小板源性生长因子（ＰＤＧＦ）基因表达的影响。结果表明，缺氧能明显增加肺动脉内皮细胞ＰＤＧＦ一Ｂ链ｍＲＮＡ的表达，而ＰＤＧＦ一Ａ链ｍＲＮＡ表达无明显影响。提示缺氧可能是体内刺激肺动脉内皮细胞ｓｉｓ／ＰＤＧＦ一Ｂ链基因表达的因素之一，通过控制肺动脉平滑肌细胞增生和收缩，在肺动脉高压血管改建中可能具有重要作用。     

低氧致鼠腺泡内肺动脉PDGF—B链蛋白表达的变化

目的：探讨血小板源性生长因子（ＰＤＧＦ）在低氧肺动脉高压血管构形重建发生中的作用。方法：应用免疫组化技术结合计算机图像分析，检测了低氧大鼠腺泡内肺动脉（ＩＡＰＡ）ＰＤＧＦ－Ｂ链蛋白表达水平。结果：常氧时，ＩＡＰＡ仅有ＰＤＧＦ－Ｂ链蛋白弱表达；低氧１天时，ＩＡＰＡ便有较强的ＰＤＧＦ－Ｂ链蛋白表达，定位于ＩＡＰＡ的内皮和中膜，低氧３天至１４天仅分布于中膜；低氧１、３、５、７、１４天各时间点ＰＤＧＦ－Ｂ链蛋白表达分别为常氧组的１．５３、１．５９、１．５６、１．６２和１．４２倍，差异有显著性（Ｐ＜０．０１）。结论：ＰＤＧＦ－Ｂ链蛋白可能参与了低氧肺动脉高压血管构形重建的发病过程     

血小板源生长因子及其受体基因表达在低氧大鼠肺中的变化

本文观察了血小板源生长因子（ＰＤＧＦ）Ａ、Ｂ链及其α、β受体基因表达在低氧大鼠肺中的变化。Ｎｏｒｔｈｅｒｎ印迹杂交显示正常大鼠肺中可表达ＰＤＧＦ－Ａ链、Ｂ链和ＰＤＧＦ－α受体、β受体的ｍＲＮＡ。随着低氧时间的延长，ｍＲＮＡ水平迅速增加。ＰＤＧＦ－Ａ、Ｂ链ｍＲＮＡ均在低氧的第二天达高峰，分别为正常的１．５１倍及１．６９倍，且Ｂ链ｍＲＮＡ基本维持在该水平至第七天。ＰＤＧＦ－α、β受体的ｍＲＮＡ在低氧第     

缺氧诱导大鼠肺动脉PDGF和c－myc基因表达增强

为了研究生长因子和原癌基因在缺氧所致肺血管结构重建中的作用，我们选用Ｗｉｓｔａｒ大鼠，置于低压仓内模拟海拔５０００米高度持续缺氧７天和１４天。与平原对照组相比，缺氧７天时肺动脉血小板源生长因子Ａ链（ＰＤＧＦ－Ａ）基因表达水平略有升高，而后有下降趋势；缺氧１４天时ＰＤＧＦ－Ｂ链３．５ｋｂｍＲＮＡ表达显著升高。点杂交结果显示：ｃ－ｍｙｃ原癌基因正常时表达水平很低。Ｎｏｒｔｈｅｒｎｂｌｏｔ可见缺氧７天时有２．２ｋｂｍＲＮＡ转录，缺氧１４天时其含量进一步增加为正常的６倍。结果表明，缺氧过程中，ＰＤＧＦ－Ａ链和Ｂ链是顺序表达的，其表达水平与缺氧性肺血管结构重组过程有一定相关。ＰＤＧＦ的促增殖作用是通过ｃ－ｍｙｃ基因产物实现的。     

Recent progress in vasopressin research on cardiovascular diseases

Arginine vasopressin (AVP) plays an important role in volume homeostasis and cardiovascular regulation. This review briefly describes recent clinical studies which evaluated the significance of AVP in cardiovascular diseases. Several AVP receptor antagonists, including tolvaptan and conivaptan, have shown promise in human trials for the treatment of heart failure. As plasma AVP concentrations are elevated in patients with heart failure in accordance with their severity, elevated AVP may contribute to their clinical syndrome of fluid retention and vasoconstriction. In some forms of hypertension, circulating AVP are also elevated; however, the precise role of AVP in the pathophysiology of hypertension is controversial. We performed a case-control study in a random sample of 620 rural residents and found an association between nonobese hypertension and -6951G/A single nucleotide polymorphism in the promoter region of the AVP V1a receptor gene. Our results suggest that AVP might contribute to the subdivision of human hypertension. Antiplatelet agents have been shown effective to prevent cardiovascular events. AVP has been known to stimulate platelet aggregation through V1a receptor. Genetic factors are thought to be involved in the heterogeneity of platelet activation. Some studies have been undertaken to identify genetic markers of platelet sensitivity to AVP.     

Genetics of osteoporosis

Osteoporosis is a common disease with a strong genetic component. In recent years, some progress has been made in understanding the genetic basis of osteoporosis. Genetic factors contribute to osteoporosis by influencing not only bone mineral density but also bone size, bone quality, and bone turnover. Meta-analysis has been used to define the role of several candidate genes in osteoporosis. Some quantitative trait loci that regulate bone mass identified by linkage studies in humans and experimental animals have been replicated in multiple populations. Genes that cause monogenic bone diseases also contribute to regulation of bone mass in the normal population. Genome-wide association studies and functional genomics approaches have recently begun to apply to genetic studies of osteoporosis. In the future, not only single gene but also the entire gene networks involved in osteoporosis and regulation of bone mass will systematically be discovered through integrative genomics.     

肠道菌群与心血管疾病关系的研究进展

人体肠道中的微生物与宿主相互作用。近年来,人们逐渐认识到肠道菌群与心血管疾病之间的关联性,甚至其中的因果关系及产生的分子机制,其中包括肠道微生物生成的氧化三甲胺(TMAO)在动脉粥样硬化性心脏病和心力衰竭的发病机制中的作用和短链脂肪酸及其受体在血压调节中的作用等代谢途径。     

Production of platelet-derived growth factor-like mitogen by smooth-muscle cells from human atheroma

Proliferation of vascular smooth-muscle cells occurs during the development of atherosclerosis and the remodeling of arteries that accompanies chronic systemic or pulmonary hypertension. To help define the signals that initiate this abnormal growth, we cultured smooth-muscle cells from human atherosclerotic plaques. These cells (n = 9) released material into their culture medium that stimulated the proliferation of aortic smooth-muscle cells to a mean (+/- SD) level 5.1 +/- 1 times that in control medium. Part of this activity was due to molecules that resemble a mitogen first isolated from platelets and known as platelet-derived growth factor (PDGF), since these cells released PDGF measured in a radioreceptor assay (355 +/- 117 pg per milliliter per 48 hours; n = 6) and since anti-PDGF antibody neutralized 38 +/- 7 percent of this mitogenic activity (range, 13 to 60 percent; n = 6 carotid-plaque isolates). Two human genes encode distinct PDGF subunits that form dimers in different combinations to create biologically active PDGF. Cells cultured from human atheroma contained mRNAs for the PDGF A chain (16 of 17 isolates) but none (of 13) that encoded PDGF B chain (the c-sis proto-oncogene product). We conclude that smooth-muscle cells from diseased human arteries can secrete mitogenic activity, some of which resembles PDGF, and that these cells express the gene for the PDGF A chain selectively. This capacity to produce an endogenous, potentially self-stimulatory (autocrine) growth factor may help to explain how replication of smooth-muscle cells can begin, even while the endothelial barrier remains morphologically intact, early in atherogenesis.     

PDGF,Pericytes and the Pathogenesis of Idiopathic Basal Ganglia Calcification (IBGC)

Platelet‐derived growth factors (PDGFs) are important mitogens for various types of mesenchymal cells, and as such, they exert critical functions during organogenesis in mammalian embryonic and early postnatal development. Increased or ectopic PDGF activity may also cause or contribute to diseases such as cancer and tissue fibrosis. Until recently, no loss‐of‐function (LOF) mutations in PDGF or PDGF receptor genes were reported as causally linked to a human disease. This changed in 2013 when reports appeared on presumed LOF mutations in the genes encoding PDGF‐B and its receptor PDGF receptor‐beta (PDGF‐Rβ) in familial idiopathic basal ganglia calcification (IBGC), a brain disease characterized by anatomically localized calcifications in or near the blood microvessels. Here, we review PDGF‐B and PDGF‐Rβ biology with special reference to their functions in brain–blood vessel development, pericyte recruitment and the regulation of the blood–brain barrier. We also discuss various scenarios for IBGC pathogenesis suggested by observations in patients and genetically engineered animal models of the disease.     

Platelet-derived growth factor expression in mesangial proliferative glomerulonephritis.

Proliferation of mesangial cells and expansion of mesangial matrix are common histologic features of proliferative glomerular disease, a frequent cause of renal failure. Proliferation of glomerular mesangial cells occurs in response to platelet-derived growth factor (PDGF), and these cells release PDGF and express PDGF A and B chain mRNAs. However, all studies relating PDGF to potential changes in glomerular structure and function to date have been performed in vitro. To explore the role of PDGF in proliferative glomerulonephritides, we studied the expression of PDGF in vivo in two animal models of IgA nephropathy with different histologic patterns of glomerular injury: either predominant mesangial proliferation or expansion of mesangial matrix. Increased expression of PDGF and PDGF B-chain mRNA in whole kidneys from diseased mice was demonstrated by immunohistochemical techniques and by solution hybridization assay, respectively. Immunohistochemically, PDGF was localized primarily within the mesangial area of glomeruli and to a much lower extent in interstitium. The increased PDGF expression correlated with the degree of hypercellularity and clinical features of the disease. In addition, PDGF expression was increased in some forms of human glomerulonephritis, characterized by mesangial proliferation. These findings suggest that PDGF may be a major contributor to mesangial cell proliferation seen in proliferative glomerulonephritides.