肝细胞癌的鞘脂组学研究进展

鞘脂是一系列新型的脂质生物调控分子,在调控细胞生长、分化、增殖以及凋亡等方面具有重要的生物学作用.鞘脂代谢紊乱可以诱发包括肝细胞癌(hepatocellular carcinoma, HCC)在内的多种疾病的发生.随着脂质组学技术的发展,越来越多的研究表明鞘脂在HCC发生、发展及转归中起到重要的作用.研究表明鞘脂可以作为诊断HCC的新型标志物,且调控鞘脂代谢通路可能成为治疗HCC的潜在靶点.本文从鞘脂的分类、代谢通路,鞘脂对肝细胞增殖与凋亡的影响,鞘脂在HCC的发生发展中的作用,以及鞘脂作为HCC诊断、治疗靶点的可能性等方面的研究现状做一综述.     

非血脂因素致血管内皮损伤时黏附分子变化的研究进展

随着社会老龄化的加快,动脉粥样硬化的发生率逐年升高。目前认为动脉粥样硬化的始动环节是血管内皮损伤,而脂质代谢异常是血管损伤的主要危险因素。现研究发现一些非脂质物质在血管损伤机制中起着重要的作用,如高同型半胱氨酸、高血糖以及高尿酸等。这些非脂质因素主要作用于血管内皮细胞,通过干扰黏附分子的表达、改变内皮细胞的病理生理状态,进而导致血管内皮的损伤,促进动脉粥样硬化病灶的形成。本文主要介绍非脂质危险因素致内皮损伤时细胞黏附分子的变化的一些作用机制,并介绍干预黏附分子表达的一些治疗靶点,对治疗动脉粥样硬化所导致的冠心病、心肌梗塞等心血管疾病具有重要的临床意义。     

铁死亡与动脉粥样硬化

铁死亡被定义为一种由脂质过氧化驱动的铁依赖性细胞死亡的调节形式,并与神经退行性疾病、肿瘤、心血管等疾病密切相关。近年来发现铁死亡在动脉粥样硬化疾病过程中发挥重要作用,本文综述了铁死亡与动脉粥样硬化中血管内皮功能障碍、巨噬细胞极化、泡沫细胞形成及血管平滑肌细胞增殖迁移等多个病理过程之间的作用及分子机制,并总结了可能对动脉粥样硬化有治疗作用的铁死亡抑制剂及相关靶点,旨在从铁死亡角度为动脉粥样硬化的防治提供新的研究策略。     

脂蛋白脂酶的调控与功能及其致动脉粥样硬化机制的研究新进展

脂蛋白脂酶能够水解极低密度脂蛋白和乳糜微粒中的甘油三酯,对清除体内过多的甘油三酯至关重要,是脂质代谢的关键酶。新近研究发现脂蛋白脂酶的合成和转运过程受到多种因素调控,并具有致动脉粥样硬化的作用,其机制存在多种途径。因此,本文主要针对脂蛋白脂酶合成和转运过程中的调控、生物学功能及其致动脉粥样硬化的主要机制研究进展作一综述,以期为动脉粥样硬化的防治寻找新的治疗靶点。     

脂联素介导的AMPK通路在冠心病脂质代谢中的分子调控机制及中医药研究进展

对脂联素介导腺苷酸活化蛋白激酶(AMPK)通路在冠心病脂质代谢中的分子调控作用机制和中医药相关的研究进展进行综述,以期为冠心病的预防治疗提供新的思路。脂联素治疗可有效激活AMPK通路,改善心肌细胞内能量代谢,降低三酰甘油和低密度脂蛋白含量,增加高密度脂蛋白含量,减轻动脉粥样硬化病变,脂联素/AMPK通路成为目前药物研发的主要靶点之一。     

川芎抗动脉粥样硬化作用机制的网络药理学与分子对接技术研究

目的使用网络药理学与分子对接技术探究川芎抗动脉粥样硬化的作用机制。方法运用中药系统药理(TCMSP)数据库筛选川芎的活性成分及质控成分,通过Swiss Target Prediction预测药物靶点。在DrugBank和DisGeNET数据库筛选出动脉粥样硬化的相关靶点。通过STRING构建靶点蛋白互作网络,运用Cytoscape绘制网络并进行拓扑学分析。使用Omicshare对相关靶点进行GO富集分析与KEGG富集分析。运用DockThor进行分子对接。结果获得川芎抗动脉粥样硬化的167个相关治疗靶点,通过网络拓扑分析发现钙敏感受体、丝裂原活化蛋白激酶3等46个靶点为核心靶点。GO富集分析发现川芎在生物过程、分子功能、细胞组成多方面影响动脉粥样硬化的发生发展。KEGG通路富集分析发现,川芎可能通过调节神经活性配体-受体相互作用、钙信号通路等多条代谢通路来发挥抗动脉粥样硬化的作用。结论运用网络药理学的方法证实了川芎抗动脉粥样硬化具有多途径、多靶点作用的特点。预测了川芎抗动脉粥样硬化的可能机制,为其后续基础研究提供了参考和理论依据。     

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。     

小凹及小凹蛋白1：胆固醇逆向转运与炎症应答的共同分子平台

脂质紊乱和炎症反应在动脉粥样硬化的发生发展中发挥了重要的作用。其中胆固醇的逆向转运能力是决定动脉粥样硬化进程与转归的关键。大量文献及研究结果显示,小凹以及小凹蛋白1既在荷脂细胞胆固醇流出中发挥转运中心和关键分子作用,也在炎症反应中发挥介导抗炎的信号转导作用。因此,小凹以及小凹蛋白1可能是荷脂细胞胆固醇逆向转运和炎症应答的共同分子平台。     

高密度脂蛋白相关1磷酸鞘氨醇对心血管的保护作用及其信号机制

<正>动脉粥样硬化是心血管疾病重要的病理生理学基础,大量的研究证明高密度脂蛋白(HDL)水平与动脉粥样硬化发生呈负相关,HDL-C已成为冠状动脉疾病的重要预测因素。HDL的组成中,蛋白质与脂质各占50%。1磷酸鞘氨醇(sphingosine 1-phosphate,S1P)是磷脂代谢的脂质介质,研究表明S1P既可以作为胞内第二信使,又可以作为细胞间信号分子,通过与细胞表面受体(S1P receptor,S1PR)结合而发挥     

Perilipin 5与心血管疾病的研究进展

脂滴积聚造成脂质代谢紊乱易诱发动脉粥样硬化性血脂异常、血压升高、促炎状态等,perilipin 5是脂滴蛋白PAT家族成员之一,其作为脂滴分解屏障可保护脂滴免受脂肪酶的分解并调控脂质代谢,perilipin 5在脂肪酸氧化能力强的组织中显著表达,提示了其在调节氧化组织中脂质储存和分解代谢的重要作用,并将脂肪分解代谢与能量需求相匹配。越来越多的研究证实,perilipin 5作为脂滴调控蛋白参与心血管疾病的发生、发展。现主要对perilipin 5在心血管疾病中的研究进展做一综述。     

Statins and inflammatory markers

Inflammation is involved in the initiation and progression of atherosclerosis and the development of atherosclerotic events. Understanding of the molecular basis of inflammation has led to the identification of markers that may be important new targets in atherothrombotic disease. Inflammatory markers, such as cell adhesion molecules, cytokines, and high-sensitivity C-reactive protein, have been shown to predict future cardiovascular events in individuals with and without established disease. 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors, or statins, inhibit the synthesis of cholesterol and have been demonstrated to reduce cardiovascular morbidity and mortality. Recently, statins have been shown to modulate several of the mechanisms of inflammation in atherosclerosis in vitro and in vivo, including reduction of inflammatory markers in clinical trials. In this article, we briefly review the biology, epidemiology, and clinical trial data on the effects of statins on some of the more promising inflammatory markers.     

动脉粥样硬化的炎症应答特征及运用

动脉粥样硬化是多种心血管疾病的共同病理基础。越来越多证据表明,炎症在动脉粥样硬化的病理生理过程中发挥重要作用。动脉粥样硬化的发展受先天性免疫与适应性免疫细胞成分调控,且与全身炎症水平相关,多种炎症因子可作为动脉粥样硬化相关心血管疾病的预测指标。同时,一些抗炎治疗的临床试验表明,降低系统性炎症因子水平能够减少心血管事件风险。文章重点阐述了炎症在动脉粥样硬化中的作用、动脉粥样硬化发展中免疫应答的特征,以及目前针对动脉粥样硬化抗炎治疗的临床研究进展,以期为动脉粥样硬化治疗提供新的策略及靶点。     

Cysteine Protease Cathepsins in Atherosclerosis and Abdominal Aortic Aneurysm

Extracellular matrix remodeling is an important mechanism in the initiation and progression of cardiovascular diseases. Cysteine protease cathepsins are among the important proteases that affect major events in the pathogenesis of atherosclerosis and abdominal aortic aneurysm, including smooth muscle cell transmigration through elastic lamina, macrophage foam cell formation, vascular cell and macrophage apoptosis, and plaque rupture. These events have been studied in cathepsin deficiencies and cathepsin inhibitor deficiencies in mice and have provided invaluable insights regarding the roles of cathepsins in cardiovascular diseases. Pharmacological inhibitions for cathepsins are under evaluation for other human diseases and may be used as clinical treatments for cardiovascular diseases in the near future. This article reviews different mechanisms for cathepsins in atherosclerosis and abdominal aortic aneurysm that could be targeted by selective cathepsin inhibitors.     

Sphingolipids, insulin resistance, and metabolic disease: new insights from in vivo manipulation of sphingolipid metabolism

Obesity and dyslipidemia are risk factors for metabolic disorders including diabetes and cardiovascular disease. Sphingolipids such as ceramide and glucosylceramides, while being a relatively minor component of the lipid milieu in most tissues, may be among the most pathogenic lipids in the onset of the sequelae associated with excess adiposity. Circulating factors associated with obesity (e.g., saturated fatty acids, inflammatory cytokines) selectively induce enzymes that promote sphingolipid synthesis, and lipidomic profiling reveals relationships between tissue sphingolipid levels and certain metabolic diseases. Moreover, studies in cultured cells and isolated tissues implicate sphingolipids in certain cellular events associated with diabetes and cardiovascular disease, including insulin resistance, pancreatic beta-cell failure, cardiomyopathy, and vascular dysfunction. However, definitive evidence that sphingolipids contribute to insulin resistance, diabetes, and atherosclerosis has come only recently, as researchers have found that pharmacological inhibition or genetic ablation of enzymes controlling sphingolipid synthesis in rodents ameliorates each of these conditions. Herein we will review the role of ceramide and other sphingolipid metabolites in insulin resistance, beta-cell failure, cardiomyopathy, and vascular dysfunction, focusing on these in vivo studies that identify enzymes controlling sphingolipid metabolism as therapeutic targets for combating metabolic disease.     

Physiological functions and clinical implications of sphingolipids in the gut

Studies of sphingolipids have become one of the most rapidly advancing fields in the last two decades. These highly diverse lipids have been known to have multiple physiological functions and clinical implications in several diseases, including tumorigenesis, inflammation, atherosclerosis and neural degenerative diseases. Unlike other organs, sphingolipids in the intestinal tract are present not only as lipid constituents in the cells but also as dietary compositions for digestion in the lumen. The present review focuses on the presence of sphingolipids and their catalytic enzymes in the gut; the metabolism and the signaling effects of the metabolites and their impacts on barrier functions, cholesterol absorption, inflammatory diseases and tumor development in the gut.     

Markers of inflammation and their clinical significance

Inflammation plays an important role in the initiation and progression of atherosclerosis and the development of atherosclerotic events. Understanding the molecular basis of inflammation has led to the identification of markers that may also serve as new targets of therapy in the management of atherothrombotic disease. Inflammatory markers, such as C-reactive protein (CRP), have been shown to predict future cardiovascular events in individuals with and without established cardiovascular disease (CVD). Statins substantially reduce cardiovascular morbidity and mortality, and recently their anti-inflammatory properties have been investigated. In this paper, we discuss biomarkers implicated in the inflammatory process leading to atherothrombosis, including CRP, adiponectin, monocyte chemoattractant protein 1 (MCP-1), CD40 ligand and lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), and the effect of statins on these markers and their potential relationship to cardiovascular events.     

Managing cardiovascular risk in patients with chronic inflammatory diseases

The role of traditional risk factors in the development of cardiovascular disease has been well studied. However, the relationship between chronic inflammatory conditions and cardiovascular risk has only recently been appreciated. Expression of numerous pro-inflammatory cytokines is common to the pathogenesis of both atherosclerosis and other chronic inflammatory diseases and may suggest that systemic inflammation independently contributes to elevated risk. This article examines the magnitude of cardiovascular risk in several of the most common chronic inflammatory diseases and summarizes currently available data to discern whether this risk is largely due to the presence of co-existing traditional risk factors for cardiovascular disease or the effect of increased systemic inflammation. Evidence is summarized to show which therapies may positively or negatively impact cardiovascular risk. Evidence is discussed in context of practical patient management tools, appropriate treatment based on risk, and treatment targets for high-risk patients. Overall, patients with chronic inflammatory diseases are at an often underestimated increase in cardiovascular risk and require individualized therapy and specific patient management strategies to address the disease process, cardiovascular risk factors, and comorbidities.     

CYR61在心血管疾病中的研究进展

富含半胱氨酸的血管生成诱导剂61?是结缔组织生长因子家族基质细胞蛋白的成员,参与许多重要生物学功能,具有广泛的生物学特性,在肿瘤性疾病、自身免疫性疾病、肾脏疾病中研究较为广泛,近年来在心血管系统中的研究越来越多,在动脉粥样硬化、心肌损伤、心肌纤维化中具有重要的生物学作用,参与了冠心病、高血压、心力衰竭等心血管疾病的发生发展。CYR61还可作为疾病的标志物,对疾病的治疗提供新的靶点。     

琥珀酸与动脉粥样硬化的研究进展

心血管疾病仍然是世界范围内的主要死亡原因,并且年轻/中年人(18～45岁)的心血管疾病发病率依然呈上升趋势.对心血管疾病的早期诊断、预警以及治疗是当前医学研究领域中重要的课题.动脉粥样硬化是多种心血管疾病的病理生理学基础,近来的研究表明,三羧酸循环中间体参与动脉粥样硬化的发生、发展进程,并且可能是动脉粥样硬化早期诊断以...