肠道菌群——心血管疾病中医药调节的新靶点

肠道菌群在人类的健康维护与疾病发展中有重要的作用,其结构和功能的失调与动脉粥样硬化、糖尿病、肥胖、高血压病、冠心病等心血管疾病的发生密切相关;其代谢产物氧化三甲胺(TMAO)的增加也被认为是影响心血管疾病预后的一个独立危险因素。系统阐述肠道菌群及其代谢产物在心血管疾病发病机制中的作用,结合中医药对肠道菌群干预的研究进展,提出中医药靶向调节肠道菌群及其代谢产物,可能成为未来心血管疾病中医药研究的新方向。     

肠道菌群代谢物在心血管疾病中的作用

肠道菌群在人体疾病的发生发展中具有重要作用。肠道菌群代谢宿主摄入饮食形成的代谢产物,穿透肠上皮屏障或以其他方式进入体循环,进而激活一系列信号通路影响宿主生理过程。肠道菌群代谢物多种多样,各种代谢物如何进入体循环影响心血管系统及其在心血管疾病中发挥作用的分子机制,目前已有大量研究报道。本文就几种常见肠道菌群代谢物在高血压、动脉粥样硬化及心力衰竭等心血管疾病中的作用和分子机制进行综述,为心血管疾病的治疗提供新的方向。     

肠道菌群相关代谢产物与心血管疾病的关系研究进展

<正>心血管疾病尤其是动脉粥样硬化和高血压,是世界卫生组织(WHO)主要的公共卫生保健项目[1]。日益增多的研究结果表明肠道菌群会对心血管疾病(CVD)产生一定影响,这种发现能够为治疗心血管疾病提供新的可能和方向。肠道菌群能够在肠道中产生具有一定生物活性的代谢产物,这些肠道菌群相关代谢产物会在宿主生理各方面发挥作用,因此这些肠道菌群相关代谢产物逐渐被共同认为是人体的第九大系统[2]。肠道菌群在许多方面对人体健康至关重要,例如形成肠道上皮屏障,调节免疫功能,消化宿主无法消化的营养素,     

肠道菌群与心血管疾病相关:现状与未来

肠道菌群组成、特异性菌种或菌群的变化与各类疾病的发生有密切的相关性.本文系统阐述了肠道菌群失调与高血压、动脉粥样硬化、心肌梗塞和心力衰竭等心血管疾病的相关性,肠道菌群的种类变化和可能的致病机制,肠道菌群失调可能是促进心血管疾病发生的原因之一.调控肠道菌群有望作为心血管疾病的潜在治疗新靶点,如应用抗生素降低血压、益生菌调节高脂血症和降压;采用干扰肠道菌群代谢活性的药物,如降低氧化三甲胺水平来防治心血管疾病,通过地中海式饮食来预防心血管疾病.     

肠道菌群与心血管疾病

肠道菌群是一个数量庞大种类繁多的复杂生态系统,参与调节物质和能量代谢、机体免疫、组织器官发育等重要的生理过程,其结构和功能的稳态失调参与高血压、动脉粥样硬化、冠心病、心肌梗死、心力衰竭以及心律失常等心血管疾病的发生发展。本文旨在阐明肠道菌群及相关代谢产物与心血管疾病研究的新进展,为心血管疾病的防治提供新的思路,为未来开展肠道菌群与心血管疾病的研究指明发展方向。     

心肠对话:肠道菌群在心血管疾病中的作用

心血管疾病(CVD)是对人类健康构成极大威胁的一类疾病,其发生、发展往往受遗传与环境的多种因素影响。肠道菌群是人体内数目最大的菌群库,影响宿主的生理代谢,近年来肠道菌群与宿主间的相互作用逐渐受到重视。肠道微生物群在人类健康和疾病中发挥着重要作用,许多研究证实了肠道菌群及其代谢产物可从血脂异常、2型糖尿病、高血压、动脉粥样硬化、心力衰竭等多个方面影响CVD。因此,以肠道菌群作为CVD治疗靶点的方案值得探索。本文将对肠道菌群在CVD发病机制中的作用及通过调节肠道菌群治疗CVD的方法进行系统综述。     

肠道菌群-TMA-TMAO代谢途径与心血管疾病的研究进展

肠道菌群紊乱与心血管疾病的发生发展密切相关。肠道微生物利用富含胆碱或三甲胺(TMA)结构的物质代谢生成氧化三甲胺(TMAO),而TMAO在心血管疾病如冠心病、动脉粥样硬化、高血压等的发生和发展中起着重要作用。该文就TMAO与心血管疾病关系和肠道菌群-TMA-TMAO代谢途径干预方法的研究进展进行综述。     

肠道菌群失调与动脉粥样硬化相关心血管疾病

肠道菌群失调对动脉粥样硬化相关心血管疾病有重要影响。心血管疾病的诸多危险因素,如高脂血症、肥胖、2型糖尿病和高血压均与肠道菌群失调密切相关,同时肠道菌群还可通过与环境因素和遗传因素的交互作用而间接影响动脉粥样硬化疾病的进展。因此,纠正肠道菌群失调可能作为治疗心血管疾病的新策略。     

支链氨基酸与心血管疾病的关系及干预措施研究进展

大量研究证实支链氨基酸（branched-chain amino acids,BCAAs）在心血管疾病如冠心病、动脉粥样硬化、高血压等的发生和发展中起着重要作用,且宿主BCAAs水平的升高与饮食、肠道菌群、疾病和遗传等因素均密切相关。从因果关系上看,肠道菌群紊乱促进了心血管疾病的发生发展,且部分肠道微生物参与BCAAs的生物合成,直接影响宿主外周BCAAs水平。近年来,从宿主和肠道菌群的角度干预BCAA代谢已成为国内外防治心血管疾病的研究热点。现就BCAAs与心血管疾病关系和肠道菌群-BCAAs代谢途径干预方法的研究进展进行综述。     

肠道菌群及其代谢产物与动脉粥样硬化的研究进展

肠道菌群的组成、结构变化与心血管疾病的发生、发展有着密切关系。近年来研究发现依赖菌群的代谢产物氧化三甲胺诱发动脉粥样硬化的发生,并与主要不良心血管事件明显呈正相关。本文就肠道菌群参与调控的元代谢途径与动脉粥样硬化之间的作用机制及研究进展进行阐述。     

多不饱和脂肪酸代谢与动脉粥样硬化的关系

动脉粥样硬化是多因素共同作用引起的,其发病机制复杂,目前尚未完全阐明。多不饱和脂肪酸作为脂肪酸家族中的一员,是哺乳动物生长发育的关键营养物质,其摄入种类和摄入量以及脂肪酸去饱和酶均能影响动脉粥样硬化性疾病的进程。脂肪酸去饱和酶基因簇能够调控脂肪酸去饱和酶的活性并进一步影响动脉粥样硬化。基于代谢和遗传学的观点,本文综述了多不饱和脂肪酸在脂肪酸去饱和酶的调节下对动脉粥样硬化影响的研究进展,并总结了脂肪酸去饱和酶基因簇变异与动脉粥样硬化性心血管疾病之间的关系。     

Biobanking in atherosclerotic disease, opportunities and pitfalls

Cardiovascular disease is the leading cause of death in Western countries and current research is still focusing on optimizing therapeutic approaches in the battle against this multifactorial disease. Concepts regarding the pathogenesis of many cardiovascular diseases originate from observations of human atherosclerotic tissue obtained from autopsies or during vascular surgery. These observations have helped us to disentangle the pathophysiology of atherosclerosis. However, identifying vulnerable patients, those prone to developing cardiovascular complications, remains difficult. The search for predictive cardiovascular biomarkers continues and large, well organized biobanks are needed to discover or validate novel biomarkers. Biobanks are an extremely valuable resource that enables us to study the influence of both genetic and environmental factors on the development of multifactorial diseases such as atherosclerosis. This review will focus on the advantages and pitfalls in atherosclerotic biobanking.     

髓过氧化物酶在冠状动脉粥样硬化研究中的新进展

目前的研究均支持炎症在冠状动脉粥样硬化性疾病中具有举足轻重的地位,炎症细胞与血管内环境中的细胞、细胞因子、炎症介质等的相互作用极其复杂,作为中性粒细胞活化标志物的髓过氧化物酶已被发现能参与冠状动脉粥样硬化的全过程,揭示粥样斑块的早期改变,为临床的早期诊断及治疗指出了新的方向.     

Cardiovascular Disease in Systemic Lupus Erythematosus: The Role of Traditional and Lupus Related Risk Factors

Atherosclerosis is a chronic inflammatory disorder characterized by immune cell activation, inflammation driven plaque formation and subsequent destabilization. In other disorders of an inflammatory nature, the chronic inflammatory state per se has been linked to acceleration of the atherosclerotic process which is underlined by an increased incidence of cardiovascular disease (CVD) in disorders such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and antiphopholipid (Hughes) syndrome (APS). SLE is an autoimmune disease that may affect any organ. Premature coronary heart disease has emerged as a major cause of morbidity and mortality in SLE. In addition to mortality, cardiovascular morbidity is also markedly increased in these patients, compared with the general population. The increased cardiovascular risk can be explained only partially by an increased prevalence of classical risk factors for cardiovascular disease; it also appears to be related to inflammation. Inflammation is increasingly being considered central to the pathogenesis of atherosclerosis and an important risk factor for vascular disease. Recent epidemiologic and pathogenesis studies have suggested a great deal in common between the pathogenesis of prototypic autoimmune disease such as SLE and that of atherosclerosis.We will review traditional risk factors for CVD in SLE. We will also discuss the role of inflammation in atherosclerosis, as well as possible treatment strategies in these patients.Key Words: Cardiovascular disease, systemic lupus erythematosus, atherosclerosis.     

Quantification of isoprostanes as indices of oxidant stress and the risk of atherosclerosis in humans

Enhanced oxidant stress occurring either locally in the vessel wall or systemically is implicated in the pathogenesis of atherosclerosis in humans. Nonetheless, evidence that oxidant stress is increased in vivo in association with this disease and that it can be quantified in living human beings has been lacking because of the unavailability of biomarkers to assess oxidant stress in humans. Recently, the development of methods to quantify the F(2)-isoprostanes (IsoPs), prostaglandin (PG)-like compounds derived from the free radical-catalyzed peroxidation of arachidonic acid, has allowed, for the first time to the author's knowledge, a facile and accurate assessment of oxidant stress in vivo. The purpose of this brief review is to discuss the usefulness of quantifying IsoPs as an index of oxidative injury in association with atherosclerosis. F(2)-IsoPs can be measured in human biological fluids, such as plasma and urine, using highly precise assays. They have been shown to be increased in association in with a number of atherosclerotic risk factors, including cigarette smoking, hypercholesterolemia, diabetes mellitus, and obesity, among others. In addition, recent evidence suggests their quantification may represent an independent marker of atherosclerotic risk. A reduction in cardiovascular risk factors is associated with a decrease in IsoP formation in humans. Despite the fact that the role of oxidant stress in the pathogenesis of atherosclerosis is a hotly debated issue, current evidence suggests that the IsoPs represent a biomarker that has the potential to be of great importance in the assessment of human atherosclerotic cardiovascular disease. Enhanced oxidant stress occurring either locally in the vessel wall or systemically is implicated in the pathogenesis of atherosclerosis in humans. Nonetheless, evidence that oxidant stress is increased in vivo in association with this disease and that it can be quantified in living human beings has been lacking. Recently, the development of methods to quantify the F2-isoprostanes (IsoPs) has allowed a facile and accurate assessment of oxidant stress in vivo. The purpose of this brief review is to discuss the usefulness of quantifying IsoPs as an index of oxidative injury in association with atherosclerosis.     

The role of inflammation, humoral and cell mediated autoimmunity in the pathogenesis of atherosclerosis

The pathogenesis of atherosclerosis has not been well defined and many questions remain unanswered. Many studies have discussed the importance of inflammation as the first step in promoting endothelial dysfunction and atherosclerosis.The association of inflammatory markers such as fibrinogen and C reactive protein (CRP) with atherosclerosis and cardiovascular/cerebrovascular clinical events reinforces the pivotal role that inflammation plays in the atherosclerotic process.The humoral and cellular autoimmune response against antigens expressed in the endothelium and the greater prevalence of atherosclerosis in immune-mediated rheumatic diseases such as Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus (SLE) strongly suggest the involvement of autoimmunity in the atherosclerotic process. The role of inflammation and autoimmune responses in atherosclerosis are discussed in order to better understand their close link on its pathogenesis.     

肠道菌群在炎症性肠病发生中的作用

炎症性肠病（IBD）是一种慢性非特异性肠道炎症性疾病．其明确病因和发病机制至今仍不清楚。近年来随着微生态学的发展．肠道菌群与IBD发病的关系日益受到关注。多项证据表明IBD患者存在肠道菌群紊乱。本文就肠道菌群在IBD发生中作用的研究进展作一综述。     

The fate of endothelial function testing: rationale and design of the Firefighters And Their Endothelium (FATE) study

Endothelial dysfunction plays a pivotal role in the development and progression of atherosclerotic vascular disease. The endothelium is strategically located between blood and vascular smooth muscle, making it both vulnerable to a variety of injurious stimuli but also available for interrogation as a marker of vascular health. Firefighters And Their Endothelium (FATE) is a prospective, longitudinal cohort study designed to assess the relationship between endothelial function, emerging cardiovascular risk factors and ultimately atherosclerotic vascular disease. It is hypothesized that participants with impaired endothelial function will be at increased risk of atherosclerotic complications. This Canadian initiative will recruit 1600 middle-aged participants with no known history of cardiovascular disease to be followed for cardiovascular events over the next decade. Quantitative B-mode ultrasound will be employed to assess endothelial function and subclinical atherosclerosis. This research is designed to redefine the approach to the primary prevention of atherosclerosis.