心血管活性多肽与动脉粥样硬化

心血管活性多肽是一类小分子多肽,对心血管系统的功能具有重要的调节作用,是心血管自稳态调节的重要的旁/自分泌因子,其功能紊乱具有重要的发病学意义。近年的研究发现心血管局部旁/自分泌功能紊乱在动脉粥样硬化的发病过程中具有重要意义,如肾素-血管紧张素系统(renin angiotensin system,RAS)、心房钠尿肽(natriuretic peptides,NPs)、尾加压素II、生长抑素、肾上腺髓质素家系等在动脉粥样硬化的发生和发展中具有重要作用。     

蛋白质来源活性多肽与心血管保护的新进展

心血管活性多肽是一种重要的生物活性多肽,研究发现了一系列活性多肽对心血管系统的自稳态调节起到非常重要的作用,包括中介素(IMD)、Apelin、胃饥饿素(Ghrelin)、胰高血糖素样肽(GLP1)、成纤维细胞生长因子(FGF21)等。这些活性多肽组织分布广泛,分子量小,免疫原性低,合成和代谢过程迅速,分泌后以配体与受体作用形式,通过细胞内多种信号通路调节心血管生理和病理生理过程,例如,血管的舒缩和新生、心脏缺血损伤后糖脂代谢及心肌重塑过程等。本文将对我们所研究的中介素以及其它几种重要的具有心血管保护作用的活性多肽及其在心血管发病中意义的研究进展做一综述。     

蜘蛛抗菌肽研究进展

蜘蛛活性多肽研究主要集中于蜘蛛毒液中作用于离子通道的神经毒素多肽。但近年来,一些蜘蛛抗菌肽不断被分离纯化,其结构和抗菌活性也被广泛深入研究,这将成为蜘蛛活性多肽研究领域的一个新热点。在蜘蛛毒液和血液中,存在不同种类的抗菌肽,其多肽长度、结构、抗菌作用各不相同。而且,有些抗菌肽甚至具有抗肿瘤作用。概述了蜘蛛抗菌肽在结构和功能方面的研究进展。     

一新种的兔内皮素B受体基因克隆和全序列分析

198 8年 ,Ｙａｎａｇｉｓａｗａ和其同事在培养的猪主动脉内皮细胞上清中分离到能对离体的猪冠状动脉产生收缩作用的多肽即内皮素 (Ｅｎｄｏｔｈｅｌｉｎ) ,简称为ＥＴ[1] 。ＥＴ不仅具有强大的缩血管作用 ,而且是体内多种细胞的促分裂剂 ,对心血管、肾脏、呼吸、消化、神经、生殖、内分泌各系统均有作用 ;更为重要的是 ,在多种疾病中 ,它又作为一种致病因子参与疾病的发生 ,具有重要的病理生理意义。ＥＴ只有与靶细胞上特异的ＥＴ受体结合 ,启动一系列细胞内信息传递系统 ,其中主要是磷酸肌醇系统 ,调节胞内钙浓度 ,才得以发挥其效应。在人…     

Apelin及其生物学效应

Apelin是Tatemoto等利用反向药理学方法从牛胃分泌物中提取并纯化出的孤儿G蛋白偶联受体——血管紧张素受体AT1相关的受体蛋白(putativereceptorproteinrelatedtotheangiotensinreceptorAT1,APJ)的天然配体。Apelin及其受体APJ在体内分布广泛,以内分泌、旁/自分泌的方式调节心血管系统稳态、水盐平衡等,是一种重要的生理调节肽。有意义的是,Apelin还是一种免疫调节肽,可通过与其受体APJ结合抵抗病毒的入侵,抑制淋巴细胞胆碱能活性,参与免疫缺陷疾病和获得性免疫缺陷综合征(acquiredimmunedeficiencysyndrome,AIDS)免疫反应,调节免疫炎症因子生成,在调节免疫反应中起一定作用。作为心血管活性肽Apelin具有扩张血管、降低血压和增强心肌收缩力的效应;心血管疾病中,Apelin及其受体APJ均有不同程度的变化,在心力衰竭及心肌重塑中具有重要调节意义。     

芋螺毒素MⅦA研究进展

来自芋螺(Conus)的芋螺毒素(conotoxin)是一类具有独特神经药理活性作用的多肽,它们能够高特异选择性识别、作用其受体,这是在五千万年进化史中与其受体相互作用形成的。其中,w-芋螺毒素MⅦA来自致幻芋螺(Conusmagus),是一种高选择性的N-型电压敏感型Ca^2 通道阻断剂。研究表明它具有强大的镇痛活性,并对脑缺血所造成的神经损伤具有保护作用。本综述芋螺毒素MⅦA的相关基础、临床前及临床研究。     

细胞外钙调素——一种植物中的多肽信使?

钙调素历来被认为是细胞内钙信号的多功能受体蛋白,国内外10多年的研究已证实,它普遍存在于人、动物细胞外与植物质外体.我们的工作证明了钙调素不仅普遍存在于植物细胞外,而且在胞外位点具有促进悬浮培养细胞及其原生质体的增殖、调节花粉萌发与伸长和促进rbc小亚基基因的光不依赖性表达等多种重要生物学功能.在花粉体系中,还证明了胞外钙调素具有跨膜与胞外信号转导机制,其中包括异三聚体G蛋白、PLC/IP3/IP3R和胞内钙信号等组分的参与.因此,认为细胞外钙调素可能是植物中的一种多肽信使,这对传统上认为植物中不存在进行胞间通讯的多肽信使的观点,提出了新的质疑.     

嗜铬颗粒蛋白A研究进展

嗜铬颗粒蛋白A(Chromogranin A,CGA)属于独特的酸性可溶性蛋白质家族,遍布于动物内分泌系统、神经系统和免疫系统,与其他激素和多肽共贮存、共分泌.在CGA上有许多碱性氨基酸对,成为潜在的激素原转化酶切割位点.很多切割产物已经被鉴定,其中有些具有生物学功能.近年的研究表明,在多种病理、生理状态下,CGA及其衍生片段在组织中含量升高,发挥抑制性生理功能或作为疾病诊断指标.嗜铬颗粒蛋白A的N端衍生片段在机体防御系统中的抗菌功能、在心血管系统中的抗血管收缩功能已被阐明,使其作为临床候选药物具有巨大潜力;CGA完整片段在内分泌肿瘤和神经内分泌肿瘤中含量升高,可作为内分泌肿瘤和神经内分泌肿瘤诊断指标,但其在肿瘤发生过程中的作用还未见报道.     

Apelin的生理与病理功能

多肽Apelin广泛存在于各种组织中,通过自分泌和旁分泌等信号途径发挥重要的生物学效应. 近年来,对Apelin的研究日益增多,发现其在心血管、神经、肾、肺等系统中均有非常重要的作用.同时,Apelin在体液平衡及肥胖的进程中也扮演了重要的角色.Apelin及其受体系统存在如此广泛,功能如此之多,暗示了其作为多个疾病进程中的关键因子.近期对Apelin功能的认识从系统、组织水平转向分子水平.随着研究的深入,Apelin有望成为治疗相关疾病的新的靶分子.本文对Apelin参与重要心血管疾病、神经疾病、肥胖症及关节炎等生理与病理过程做一综述.     

细胞因子受体的组成,结构功能及信号传导机制

细胞因子受体种类繁多,分属于不同受体超家族。活化受体的功能可分为：ＰＴＫ型受体或其结合蛋白具有ＰＴＫ活性、丝／苏氨酸蛋白激酶型受体以及与Ｇ蛋白耦联的受体等。不同受体与其配体结合后,通过对受体后信号传导成分的可逆的磷酸化反应传递信号,最终通过对其终端成分,如酶活力、基因表达、细胞骨架蛋白的功能、膜通透性等的调节,导致细胞的生物效应。     

生物肽降压作用机制及定量构效关系的研究

高血压是心脑血管疾病的首要危险因素,严重威胁着人类的生命健康。生物肽能有效预防和治疗高血压,并且具有安全可靠、作用多靶点等特点。大量的研究表明生物肽存在多种降压作用机制,深入研究降压机制可为中药治疗高血压提供新思路。本文综述了近年来生物肽潜在的降压机制,并探索其定量构效关系,旨在为中药药效组分的研究以及相关药物设计和筛选提供理论指导。     

Cardio-protective role of Humanin in myocardial ischemia-reperfusion

Mitochondria-derived peptides (MDPs) are bioactive peptides encoded by and secreted from the mitochondria. To date, a few MDPs including humanin, MOTS-c and SHLP1–6, and their diverse biological functions have been identified. The first and most studied MDP is humanin, a 24-amino-acid poly peptide. It was first identified in 2001 in the surviving neurons of patient with Alzheimer's disease, and since then has been well characterized for its neuro-protective effect through inhibition of apoptosis. Over the past two decades, humanin has been reported to play critical roles in aging as well as multiple diseases including metabolic disorders, cardiovascular diseases, and autoimmune disease. Humanin has been shown to modulate multiple biological processes including autophagy, ER stress, cellular metabolism, oxidative stress, and inflammation. A role for humanin has been shown in a wide range of cardiovascular diseases, such as coronary heart disease, atherosclerosis, and myocardial fibrosis. In this minireview, we will summarize the literature demonstrating a role for humanin in cardio-protection following myocardial ischemia-reperfusion induced injury and the potential mechanisms that mediate it.     

N 端脑钠肽前体在心血管疾病中的研究进展

N端脑钠肽前体(NT-proBNP)为脑钠肽(BNP)生成过程中产生的无活性肽段残片,其与BNP等摩尔量分泌。近年来,NT-proBNP的检测在心血管领域的作用越来越得到国内外学者的关注。NT-proBNP在心血管疾病的诊断、预后、分级等方面都具有重要的价值。本文主要介绍NT-proBNP在心血管疾病中的研究进展。     

N端脑钠肽前体在心血管疾病中的研究进展

N端脑钠肽前体（NT-proBNP）为脑钠肽（BNP）生成过程中产生的无活性肽段残片,其与BNP等摩尔量分泌。近年来,NT-proBNP的检测在心血管领域的作用越来越得到国内外学者的关注。NT-proBNP在心血管疾病的诊断、预后、分级等方面都具有重要的价值。本文主要介绍NT-proBNP在心血管疾病中的研究进展。     

Discovery of recently adopted orphan receptors for apelin,urotensin II,and ghrelin identified using novel radioligands and functional role in the human cardiovascular system

Using novel synthetic radioligands, we have discovered receptors for the recently paired apelin (APJ orphan receptor), ghrelin (GHS orphan receptor), and urotensin II (orphan GPR14) in the human cardiovascular system and determined their anatomical localisation. In addition, we have established functional vasoactive properties for these three peptides as potential vasoconstrictor/vasodilator mediators and provided evidence for alteration of receptor density in cardiovascular disease. We find that receptors for apelin, ghrelin, and urotensin II are widely distributed in human cardiovascular tissue, suggesting perhaps vasoactive roles for these peptides in human vascular physiology and a potential role in pathophysiology. Apelin and urotensin II are potent vasoconstrictors with low efficacy, consistent with their low receptor density. Ghrelin receptor density was increased (approximately three- to fourfold) with atherosclerosis of coronary artery disease and accelerated atherosclerosis of saphenous vein grafts, compared with normal vessels, highlighting a potentially beneficial role for this novel vasodilator peptide in human vascular disease. Our approach has demonstrated one successful strategy for translating genetic information encoding recently paired orphan receptor ligands into discovery of function. This study has the advantage of focussing on the actual disease processes, which allow the more precise identification of novel therapeutic targets.     

Milk derived bioactive peptides and their impact on human health – A review

Milk-derived bioactive peptides have been identified as potential ingredients of health-promoting functional foods. These bioactive peptides are targeted at diet-related chronic diseases especially the non-communicable diseases viz., obesity, cardiovascular diseases and diabetes. Peptides derived from the milk of cow, goat, sheep, buffalo and camel exert multifunctional properties, including anti-microbial, immune modulatory, anti-oxidant, inhibitory effect on enzymes, anti-thrombotic, and antagonistic activities against various toxic agents. Majority of those regulate immunological, gastrointestinal, hormonal and neurological responses, thereby playing a vital role in the prevention of cancer, osteoporosis, hypertension and other disorders as discussed in this review. For the commercial production of such novel bioactive peptides large scale technologies based on membrane separation and ion exchange chromatography methods have been developed. Separation and identification of those peptides and their pharmacodynamic parameters are necessary to transfer their potent functional properties into food applications. The present review summarizes the preliminary classes of bioactive milk-derived peptides along with their physiological functions, general characteristics and potential applications in health-care.     

The role of CRH in behavioral responses to stress

Corticotropin-releasing hormone (CRH) and urocortin in the central nervous system affect behavior and can enhance behavioral responses to stressors. The action of CRH-related peptides is mediated through multiple receptors that differ markedly in their pharmacological profiles and anatomical distribution. Comparative pharmacology of CRH receptor agonists suggests that CRH, urocortin, sauvagine and urotensin consistently mimic, and CRH receptor antagonists consistently lessen, functional consequences of stressor exposure. Recently, important advances have been made in understanding the CRH system and its role in behavioral responses to stress by the development of specific CRH receptor antagonists, application of antisense oligonucleotides and development of transgenic mice lacking peptides and functional receptors. This review summarizes recent findings with respect to components of the CRH system and their role in stress-induced behavioral responses.     

Functional duality of kinin receptors in pathophysiology

Kinins are autacoid peptides and central neuromediators involved in cardiovascular regulation, inflammation and pain. Their effects are mediated by two transmembrane G-protein-coupled receptors denoted as B1 and B2. While the B2 receptor is constitutive, the B1 receptor is inducible and up-regulated in the presence of cytokines, endotoxins or during tissue injury. The B2 receptor is believed to play an important role in the beneficial effects of angiotensin-1 converting enzyme inhibitors used in the treatment of cardiovascular diseases, yet it is involved in the acute phase of inflammation and of somatic and visceral pain. Conversely, the B1 receptor participates in the chronic phase of these responses and is likely to play a strategic role in diseases with a strong immune component such as rheumatoid arthritis, multiple sclerosis, septic shock and diabetes. A dual function for the B1 receptor is also reported in some pathologies in which it can exert either a protective (multiple sclerosis and septic shock) or harmful (pain and inflammation) effect. Therefore, the use of antagonists for these receptors as clinical therapeutic agents requires a rigorous evaluation of the potential side effects.     

利钠肽家族基因与心血管疾病研究新进展

利钠肽家族是一组由心肌细胞分泌的激素,主要包括A型、B型和C型利钠肽,具有相似的基因结构和生理学效应,可对心血管系统产生血压调节、抗心肌肥厚、抗心肌纤维化和抗心肌弛缓等保护作用。利钠肽受体A、B和C亦介导多种生理活性,调节心血管稳态。利钠肽受体A选择性结合A型、B型利钠肽。利钠肽受体B结合C型利钠肽。利钠肽受体C结合各型利钠肽,通过受体介导的内化和退化作用清除血液循环中利钠肽。对利钠肽家族及其受体基因单核甘酸多态性及功能研究显示,其与多种心血管疾病(房颤、高血压、心力衰竭等)的易感性相关。利钠肽家族及其受体基因缺失的转基因小鼠表现为心肌肥厚、心肌纤维化,与高血压、心肌病及心力衰竭的发生发展相关。各种导致心肌肥厚和缺血性损伤的刺激均参与利钠肽及其受体基因的表达调控。临床将脑钠肽作为左室功能障碍和心力衰竭失代偿的一个预测指标。静脉注射重组脑钠肽已经成为治疗急性心力衰竭的有效手段。深入了解利钠肽家族基因变异及其信号调控有助于探索心血管疾病的病理生理机制,为临床诊疗开辟新思路。     

利钠肽家族基因与心血管疾病研究新进展

利钠肽家族是一组由心肌细胞分泌的激素, 主要包括A型、B型和C型利钠肽, 具有相似的基因结构和生理学效应, 可对心血管系统产生血压调节、抗心肌肥厚、抗心肌纤维化和抗心肌弛缓等保护作用。利钠肽受体A、B和C亦介导多种生理活性, 调节心血管稳态。利钠肽受体A选择性结合A型、B型利钠肽。利钠肽受体B结合C型利钠肽。利钠肽受体C结合各型利钠肽, 通过受体介导的内化和退化作用清除血液循环中利钠肽。对利钠肽家族及其受体基因单核甘酸多态性及功能研究显示, 其与多种心血管疾病(房颤、高血压、心力衰竭等)的易感性相关。利钠肽家族及其受体基因缺失的转基因小鼠表现为心肌肥厚、心肌纤维化, 与高血压、心肌病及心力衰竭的发生发展相关。各种导致心肌肥厚和缺血性损伤的刺激均参与利钠肽及其受体基因的表达调控。临床将脑钠肽作为左室功能障碍和心力衰竭失代偿的一个预测指标。静脉注射重组脑钠肽已经成为治疗急性心力衰竭的有效手段。深入了解利钠肽家族基因变异及其信号调控有助于探索心血管疾病的病理生理机制, 为临床诊疗开辟新思路。