色素上皮衍生因子与动脉粥样硬化相关性的研究进展

随着人们生活水平的不断进步,动脉粥样硬化(AS)日益成为危害人类健康的杀手。炎症反应和氧化应激是AS发展的关键步骤,血栓形成和新生血管生成与AS斑块不稳定密切相关,甚至引发AS斑块破裂和急性冠状动脉综合征。目前研究表明,色素上皮衍生因子(PEDF)具有抗炎、抗氧化、抗血管新生和抑制血栓形成等特性,对AS发挥保护作用。本文就PEDF与AS之间关系的研究进展做一综述。     

色素上皮衍生因子与糖尿病肾病

色素上皮衍生因子(PEDF)是丝氨酸蛋白酶抑制剂超家族成员之一,其主要生物学作用是营养神经、神经元保护、抗氧化应激、抗炎性反应、抑制新生血管形成等.越来越多的研究显示,PEDF在糖尿病肾病中可发挥独特的保护作用,如减少肾小球细胞外基质生成、预防肾脏纤维化,并通过抑制肾脏炎性反应和氧化应激反应而抑制肾小球毛细血管内皮细胞增生、调节血管的渗透性,从而减少尿蛋白的生成.因此,PEDF有望成为糖尿病肾病的一个治疗靶点.     

色素上皮衍生因子抗炎机制的相关研究进展

动脉粥样硬化(AS)作为心血管疾病(CVD)的主要病理基础,严重危害人类健康。AS实质是一种慢性炎症性疾病,抑制AS过程中的炎症反应或可成为延缓AS的关键。诸多研究已证实色素上皮衍生因子(PEDF)可通过抑制炎症反应进而延缓AS的发展,且作用机制复杂。本文就PEDF抗炎作用的机制做一综述。     

色素上皮衍生因子与糖尿病肾病

色素上皮衍生因子(PEDF)是一种高效、天然的血管增生抑制剂,具有神经营养保护、调节血管通透性和高效抑制血管生成等作用.近年来有研究表明,PEDF的减少与糖尿病肾病(DN)有密切关系,PEDF可抑制转化生长因子-β1(TGF-β1)和结缔组织生长因子(CTGF)的表达,抑制细胞外基质(ECM)的聚积,提示其具有抗纤维化活性,同时可通过调节肾脏脉管系统发展和维持肾自身稳态来发挥对DN的保护作用.PEDF可抑制DN的发生、发展,可能成为DN治疗的一种新方向.     

色素上皮衍生因子在心血管疾病中的作用

色素上皮衍生因子(PEDF)生物学功能复杂,既往研究证明其在眼部与神经系统的生理稳态和病理过程中扮演重要角色。近年发现PEDF在心血管系统与脂肪组织表达量高,PEDF与代谢综合征、动脉粥样硬化、高血压、心衰与心肌梗死等心血管疾病关系密切但机制尚未完全阐明,它可能在这些疾病的病理过程中发挥重要作用。PEDF有望成为一个新的有效的治疗心血管疾病的靶点和疾病预测分子。     

色素上皮衍生因子与糖尿病肾病

糖尿病肾病(DN)是糖尿病(DM)重要微血管并发症之一,患病人数逐年上升,成为终末期肾病和DM患者死亡的重要原因.美国肾脏病资料系统(United States Renal Data System,USRDS)的统计显示~([1]),超过30%的终末期肾衰竭(ESRF)为DN所致,预计到2030年,DM患者将达到3.6亿左右,近40%的患者发展为DN.     

色素上皮衍生因子与糖尿病视网膜病变

色素上皮衍生因子(PEDF)来源于人视网膜色素上皮细胞,是眼内有效的血管生成抑制剂,对保持正常眼组织透明无血管的状态有重要作用。PEDF能对抗多种促血管生成因子,有针对性地抑制病理性血管生成,延缓糖尿病视网膜病变的进展,发挥保护作用。同时,PEDF在眼部浓度降低可增加糖尿病视网膜病变的危险。其作用机制仍在探索中。外源性应用PEDF及进行基因治疗对眼部血管增生性疾病具有显著疗效。因此,深入研究可能会发现PEDF治疗临床血管增生性疾病更广泛的作用。     

色素上皮衍生因子与糖尿病大血管病变

色素上皮衍生因子是一种强有力的新生血管抑制因子,除具有神经营养、神经保护、调节血管通透性的作用,还具有改善胰岛素抵抗、抑制炎性反应、抗氧化应激、抑制血管平滑肌细胞增殖及迁移、抑制新生血管、抑制血栓形成和抑制C反应蛋白生成等效应,因此可以延缓2型糖尿病大血管并发症的发生、发展.     

色素上皮衍生因子及其单核苷酸多态性与糖尿病并发症

色素上皮衍生因子来源于人视网膜色素上皮细胞,可以通过促进活化的血管内皮细胞凋亡来抑制病理性血管的生成,是眼内有效的血管生成抑制剂。同时,色素上皮衍生因子可能通过阻断高糖诱导的TGF-β在肾脏的过度表达,起到保护肾脏的作用。色素上皮衍生因子抗炎及调节动脉内膜新生血管形成的特性也起到了阻止动脉粥样硬化进程的作用。近年来的研究显示,在糖尿病并发症患者眼部及肾脏局部组织中,色素上皮衍生因子表达量较单纯糖尿病组有所下降,血清水平则升高,提示其与糖尿病并发症密切相关。色素上皮衍生因子单核苷酸多态性与糖尿病并发症的关系也在进一步研究当中。     

色素上皮衍生因子在胃癌进展中的作用

胃癌(gastric carcinoma,GC)对人类健康来说是一大威胁,是第三大常见的癌症死亡原因.2018年,超过100万人被诊断为GC,约有78.3万人死亡.死亡率高的部分原因是无症状患者在疾病诊断较晚,转移率较高.色素上皮衍生因子(Pigment epithelial-derived factor,PEDF)表...     

色素上皮细胞衍生因子在代谢综合征中的研究进展

代谢综合征（MS）是代谢层面的心血管危险因子的聚集现象,主要包括高血压、血脂异常、糖尿病、胰岛素抵抗及腹部肥胖等。近年来MS发病率明显上升并严重危害居民的身体健康。色素上皮细胞衍生因子(PEDF)属丝氨酸蛋白酶抑制基因家族,是由多种细胞表达,具有多种生物学活性的分泌性糖蛋白。近年来多项临床试验提示PEDF参与了MS的发生发展,是一个有希望的疾病治疗靶点。本文就PEDF在MS中的作用综述。     

Antiangiogenic property of pigment epithelium-derived factor in hepatocellular carcinoma

Pigment epithelium-derived factor (PEDF) is one of the most powerful endogenous antiangiogenic reagents discovered to date. Its antiangiogenic potential in neoplastic disease remains unclear. In this study, we investigated antiangiogenic property of PEDF in hepatocellular carcinoma (HCC), a typical hypervascular tumor. In HCC cell lines, constitutive messenger RNA and protein expression of PEDF varied. Genomic DNA encoding the PEDF gene was the same in the cell lines examined by Southern blotting. In chemically induced hypoxic conditions, secreted PEDF protein was suppressed in contrast to elevation of vascular endothelial growth factor protein. When PEDF was overexpressed by gene transfer, proliferation and migration of endothelial cells were inhibited in conditioned media derived from all HCC cell lines. However, the serum concentration of PEDF, as measured by enzyme-linked immunosorbent assay, was decreased in patients with cirrhosis or HCC complicated by cirrhosis compared to healthy volunteers and patients with chronic hepatitis. According to the endothelial cell proliferation assay, the serum PEDF of patients with HCC had antiangiogenic activity. Moreover, intratumoral injection of a PEDF-expressing plasmid in athymic mouse models caused significant inhibition of preestablished tumor growth. In conclusion, PEDF plays a role in the angiogenic properties of HCC. Reduction of serum PEDF concentration associated with the development of chronic liver diseases may contribute to the progression of HCC. In addition, gene therapy using PEDF may provide an efficient treatment for HCC.     

Extracellular phosphorylation converts pigment epithelium-derived factor from a neurotrophic to an antiangiogenic factor

The pigment epithelium-derived factor (PEDF) belongs to the superfamily of serine protease inhibitors (serpin). There have been 2 distinct functions attributed to this factor, which can act either as a neurotrophic or as an antiangiogenic factor. Besides its localization in the eye, PEDF was recently reported to be present also in human plasma. We found that PEDF purified from plasma is a phosphoprotein, which is extracellularly phosphorylated by protein kinase CK2 (CK2) and to a lesser degree, intracellularly, by protein kinase A (PKA). CK2 phosphorylates PEDF on 2 main residues, Ser24 and Ser114, and PKA phosphorylates PEDF on one residue only, Ser227. The physiologic relevance of these phosphorylations was determined using phosphorylation site mutants. We found that both CK2 and PKA phosphorylations of PEDF markedly affect its physiologic function. The fully CK2 phosphorylation site mutant S24, 114E abolished PEDF neurotrophic activity but enhanced its antiangiogenic activity, while the PKA phosphorylation site mutant S227E reduced PEDF antiangiogenic activity. This is a novel role of extracellular phosphorylation that is shown here to completely change the nature of PEDF from a neutrophic to an antiangiogenic factor.     

Oxidized low density lipoprotein potentiation of Fas-induced apoptosis through lectin-like oxidized-low density lipoprotein receptor-1 in human umbilical vascular endothelial cells.

Under normal conditions, vascular endothelial cells are resistant to Fas-mediated apoptosis, although they express detectable Fas on their cell surface. Because oxidized Low density lipoprotein (Ox-LDL) is thought to promote atherogenesis, the potential role that Ox-LDL may play in Fas-mediated apoptosis was investigated in human umbilical vascular endothelial cells (HUVECs), focusing particularly on the involvement of the lectin-like Ox-LDL receptor-1 (LOX-1). HUVECs were treated with agonistic anti-Fas antibody (CH11) and Ox-LDL and then the degree of apoptosis was determined by cell death ELISA. Ox-LDL concentration-dependently sensitized Fas-mediated apoptosis. Flow cytometry demonstrated that Ox-LDL dose-dependently up-regulated cell surface Fas expression. On the other hand, treating HUVECs with Ox-LDL did not lead to any significant change in the expression of death mediators, including Fas, Fas ligand (FasL), FADD, and FLICE as assessed by multiplex polymerase chain reaction amplification. More importantly, these effects of Ox-LDL on Fas-mediated apoptosis were significantly blocked by a neutralizing LOX-1 monoclonal antibody, which can block LOX-1-mediated cellular uptake of Ox-LDL. Ox-LDL may be an important factor involved in the regulation of Fas-induced apoptosis via Ox-LDL/LOX-1 interaction in vascular endothelial cells. The results may provide insights into the pathogenesis of accelerated atherosclerosis in patients with hyperlipidemia.