糖胺聚糖在主动脉夹层发病机制中的作用

<正> 主动脉夹层是发生于主动脉的最常见灾难性疾病之一,致残率及致死率极高。目前其发病机制尚未阐明,可能是血流动力学和组织病理学等多种因素综合作用的结果,而通常认为主动脉壁本身结构异常是发病基础,血流动力学异常是促发因素。细胞外基质(ECM)是构成主动脉壁的主要成分,其异常是主动脉夹层的特征性改变之一。糖胺聚糖是重要的细胞外基质大分子,对维持主动脉壁结构和功能的正常起着重要作用,其异常改变可能是主动脉夹层发病和进展     

微血管病变与缺血性心脏病

冠状动脉微血管在心肌的血供中起着重要作用,冠状动脉微循环对冠心病的发生、发展、疗效及预后具有重要影响而备受人们重视。目前冠状动脉微血管病变主要分为X综合征和冠脉内慢血流现象,二者都与缺血性心脏病存在着密切的关系,但发病机制有所不同。X综合征主要是冠状动脉微血管痉挛所致,而冠脉内慢血流现象传统上被认为与微血管功能失调有关。此外慢血流现象可能是缺血性心脏病的一种新的发病机制,它可能代表了动脉粥样硬化和内皮功能失调的早期阶段。并且二者在治疗上有所不同。     

花生四烯酸衍生物在腹主动脉瘤发生发展中的作用

腹主动脉瘤(AAA)是老年群体常发疾病,发病率逐年上升,其容易破裂,死亡率高,目前并无有效药物可以延缓AAA的发生发展。AAA发病机制与细胞外基质降解、血管平滑肌细胞凋亡及炎症反应等密切相关。花生四烯酸衍生物广泛参与炎症反应、氧化应激等病理过程,尤其是前列腺素E2(PGE2)、前列腺素D2(PGD2)和血栓素A2(TXA2)等前列腺素,对AAA的发生发展具有重要作用。该文综述了花生四烯酸衍生物在AAA发生发展中的作用及其机制,以及药物的最新研究进展,为治疗AAA和发现新药物靶点提供思路。     

微循环异常与高血压

高血压的发病涉及多种因素多种机制,目前仍不完全清楚,微循环的异常可能参与了高血压的发生发展并在其中起重要作用,现介绍微循环异常与高血压发病、发展与治疗的关系。     

炎性细胞和主动脉固有细胞在主动脉夹层中的研究现状

主动脉夹层是指主动脉内膜撕裂, 血液经内膜撕裂口进入主动脉壁造成正常主动脉壁分离, 形成真假腔的一种凶险的心血管疾病。常见于中老年人群, 尽管发病率低, 但发病突然, 且病死率极高。主动脉夹层的诱因错综复杂, 发病机制尚未完全明确, 主要与主动脉壁结构异常、血管壁炎症反应和血流动力学有关。该文重点整理了炎性细胞和主动脉固有细胞在主动脉夹层发生发展过程中的作用, 为该疾病的治疗提供新思路。     

高血压导致主动脉夹层发病机制的研究进展

主动脉夹层的发病率明显增加,病死率高,严重威胁患者生命。在导致主动脉夹层发生的病因中,高血压是最常见的一种。目前认为,血流动力学改变、血管壁病理性改变以及分子免疫因素参与疾病的发生发展;但具体的发病机制仍不明确。现综述高血压导致主动脉夹层发病机制的研究进展,希望为进一步研究主动脉夹层的发病机制奠定基础,为主动脉夹层的防治提供理论指导。     

早期急性胰腺炎患者胰腺微循环紊乱的特点及发生机制

急性胰腺炎是一种起病急、变化快、病情复杂的疾病,其确切发病机理尚不清楚。研究发现,胰腺微循环紊乱在急性胰腺炎的发生、发展中起重要作用。现将急性胰腺炎时胰腺微循环紊乱的特点及发生机制综述如下。     

急性胰腺炎微循环障碍的发生机制及其治疗进展

近年来,越来越多的研究表明,血管收缩、血液分流、灌注不足、血液黏滞度增加以及血液凝固等微循环障碍与急性胰腺炎(AP)的发病机制密切相关。缺血再灌注损伤及氧自由基的不断产生亦可加速AP的进程。介绍了胰腺微循环的解剖学特征、胰腺微循环障碍的病理生理学机制及相关的炎症介质,以及AP微循环障碍的治疗进展,提示胰腺及全身微循环障碍可能在AP发生发展中起着重要的作用。     

急性胰腺炎与微循环障碍

急性胰腺炎（AP）为消化系统常见危重急症之一,其病因和发病机制迄今尚未完全阐明。近年关于AP与胰腺微循环之间关系的研究逐渐增多,大量实验研究显示微循环障碍在AP的发生、发展过程中起重要作用。本文就AP微循环障碍的解剖学基础、发生机制和治疗措施作一综述。     

微循环障碍与急性胰腺炎

急性胰腺炎病因及发病机制复杂,至今尚未清晰.但微循环障碍参与急性胰腺炎发病及疾病进展已成共识.本文就微循环障碍在急性胰腺炎发病机制中的表现及作用作一综述, 并提出改善微循环治疗也将是临床上治疗急性胰腺炎的一个重要措施.     

Top 10 candidate aortic disease trials

Aortic pathologies such as aneurysm, dissection and trauma are relatively common and potentially fatal diseases. Over the past two decades, we have experienced unprecedented technical and medical developments in the field. Despite this, there is a great need, and great opportunities, to further explore the area. In this review, we have identified important areas that need to be further studied and selected priority aortic disease trials. There is a pressing need to update the AAA natural history and the role for endovascular AAA repair as well as to define biomarkers and genetic risk factors as well as influence of gender for development and progression of aortic disease. A key limitation of contemporary treatment strategies of AAA is the lack of therapy directed at small AAA, to prevent AAA expansion and need for surgical repair, as well as to reduce the risk for aortic rupture. Currently, the most promising potential drug candidate to slow AAA growth is metformin, and RCTs to verify or reject this hypothesis are warranted. In addition, the role of endovascular treatment for ascending pathologies and for uncomplicated type B aortic dissection needs to be clarified.     

Influence of periodontitis on abdominal aortic aneurysms

Periodontitis is known to be a risk factor for abdominal aortic aneurysm (AAA). However, the influence of periodontitis on AAA development is to be elucidated. This article is to review the relationship between periodontitis and AAA. We focused on the roles of specific periodontopathic bacteria in AAA, matrix metalloproteinases and toll-like receptors in the pathophysiology in the section of experimental analysis. Furthermore, we showed clinical data of periodontitis in patients with AAA. We concluded that periodontal pathogens play a critical role in the AAA development.     

Role of oxidative stress in the pathogenesis of abdominal aortic aneurysms

The role of inflammation in the pathogenesis of abdominal aortic aneurysms (AAA) is well established. The inflammatory process leads to protease-mediated degradation of the extracellular matrix and apoptosis of smooth muscle cells (SMC), which are the predominant matrix synthesizing cells of the vascular wall. These processes act in concert to progressively weaken the aortic wall, resulting in dilatation and aneurysm formation. Oxidative stress is invariably increased in, and contributes importantly to, the pathophysiology of inflammation. Moreover, reactive oxygen species (ROS) play a key role in regulation of matrix metalloproteinases and induction of SMC apoptosis. ROS may also contribute to the pathogenesis of hypertension, a risk factor for AAA. Emerging evidence suggests that ROS and reactive nitrogen species (RNS) are associated with AAA formation in animal models and in humans. Although experimental data are limited, several studies suggest that modulation of ROS production or activity may suppress AAA formation and improve experimental outcome in rodent models. Although a number of enzymes can produce injurious ROS in the vasculature, increasing evidence points toward a role for NADPH oxidase as a source of oxidative stress in the pathogenesis of AAA.     

Genome wide association studies of abdominal aortic aneurysms-biological insights and potential translation applications

Abdominal aortic aneurysm (AAA) is a complex disease with important environmental risk factors and a heritability of approximately 70%. Genome wide association studies have revolutionised the study of complex disorders and offer the potential for innovative insight into disease pathogenesis and development of individualised therapeutic options. This paper reviews the progress of genome wide association studies in AAA, highlighting novel disease pathways and potential translational applications of genomic discoveries.     

miRNA在腹主动脉瘤中的研究进展

主动脉瘤是威胁人类健康的重要疾病,一般表现为主动脉病理性的扩张,以腹主动脉瘤最为常见。miRNA是一类单链非编码小RNA,广泛参与转录后基因表达的调控。随着近年研究的逐渐深入,miRNA已被视作腹主动脉瘤进展中的重要调控分子。理解miRNA在腹主动脉瘤发生发展中的调控机制,有助于疾病的早期诊断、靶向治疗及预后判断。     

Antibody directs properdin-dependent activation of the complement alternative pathway in a mouse model of abdominal aortic aneurysm

Abdominal aortic aneurysm (AAA) is a complex inflammatory vascular disease. There are currently limited treatment options for AAA when surgery is inapplicable. Therefore, insights into molecular mechanisms underlying AAA pathogenesis may reveal therapeutic targets that could be manipulated pharmacologically or biologically to halt disease progression. Using an elastase-induced AAA mouse model, we previously established that the complement alternative pathway (AP) plays a critical role in the development of AAA. However, the mechanism by which complement AP is initiated remains undefined. The complement protein properdin, traditionally viewed as a positive regulator of the AP, may also initiate complement activation by binding directly to target surfaces. In this study, we sought to determine whether properdin serves as a focal point for the initiation of the AP complement activation in AAA. Using a properdin loss of function mutation in mice and a mutant form of the complement factor B protein that produces a stable, properdin-free AP C3 convertase, we show that properdin is required for the development of elastase-induced AAA in its primary role as a convertase stabilizer. Unexpectedly, we find that, in AAA, natural IgG antibodies direct AP-mediated complement activation. The absence of IgG abrogates C3 deposition in elastase-perfused aortic wall and protects animals from AAA development. We also determine that blockade of properdin activity prevents aneurysm formation. These results indicate that an innate immune response to self-antigens activates the complement system and initiates the inflammatory cascade in AAA. Moreover, the study suggests that properdin-targeting strategies may halt aneurysmal growth.     

腹主动脉瘤血管平滑肌细胞凋亡和自噬研究

目的探讨血管平滑肌细胞(SMC)凋亡和自噬与腹主动脉瘤(AAA)发病的关系。方法采用原位末端DNA标记(TUNEL)技术观察AAA和人正常主动脉组织中SMC凋亡的情况,并用免疫组织化学分析其中LC3的蛋白表达。提取AAA和正常主动脉组织RNA,采用RT-PCR方法检测其中与自噬相关的基因Beclin1、Atg4b、Bnip3、Vps34的表达。结果 AAA组织中凋亡的SMC明显高于正常主动脉组织(P0.05);LC3蛋白在AAA中的表达高于正常主动脉组织(P0.05);AAA中Beclin1、Atg4b、Bnip3、Vps34表达水平明显高于正常主动脉组织(P0.05)。结论 SMC凋亡和自噬在AAA的发病中起重要作用。     

Lack of an effective drug therapy for abdominal aortic aneurysm

Abdominal aortic aneurysm (AAA) rupture is a common cause of death in adults. Current AAA treatment is by open surgical or endovascular aneurysm repair. Rodent model and human epidemiology, and genetic and observational studies over the last few decades have highlighted the potential of a number of drug therapies, including medications that lower blood pressure, correct dyslipidaemia, or inhibit thrombosis, inflammation or matrix remodelling, as approaches to managing small AAA. This review summarizes prior AAA pathogenesis data from animal and human studies aimed at identifying targets for the development of drug therapies. The review also systematically assesses past randomized placebo‐controlled drug trials in patients with small AAAs. Eleven previously published randomized‐controlled clinical trials testing different drug therapies aimed at slowing AAA progression were identified. Five of the trials tested antibiotics and three trials assessed medications that lower blood pressure. Meta‐analyses of these trials suggested that neither of these approaches limit AAA growth. Allocation to blood pressure‐lowering medication was associated with a small reduction in AAA rupture or repair, compared to placebo (relative risk 0.94, 95% confidence intervals 0.89, 1.00, P = 0.047). Three further trials assessed the effect of a mast cell inhibitor, fibrate or platelet aggregation inhibition and reported no effect on AAA growth or clinical events. Past trials were noted to have a number of design issues, particularly small sample sizes and limited follow‐up. Much larger trials are needed to properly test potential therapeutic approaches if a convincingly effective medical therapy for AAA is to be identified.     

Smoking and aortic diseases.

Cigarette smoking is a major vascular risk factor and in this context, it is an independent risk factor for the development of aortic disease, especially the formation and growth of abdominal aortic aneurysms (AAA). Medline was searched up to January 31, 2007 for the relevant literature for this review of the mechanisms by which smoking causes aortic wall damage and its subsequent impact on the clinical manifestation of this process. Idiopathic AAAs and aortic dissection are considered, as well as other aortic diseases (eg, Takayasu, Kawasaki, Behcet and Buerger). There is evidence suggesting an abnormal homeostasis between proteolytic and antiproteolytic activity in the vascular wall during the development of AAAs, and these mechanisms can be influenced by smoking. Smoking cessation plays an important role in the management of aortic disease.     

Abdominal aortic aneurysm

An abdominal aortic aneurysm (AAA) is defined as a localized dilation of the artery that is 1.5 times the diameter of the normal segment. The most common location for an aortic aneurysm is the infrarenal segment where a diameter that exceeds 3 cm in diameter is considered aneurysmal. Duplex ultrasonography and spiral computerized tomography are the imaging modalities most commonly performed to detect the longitudinal and transverse diameter of the aorta. The prevalence of AAA may be increasing. Smoking, male gender, and increasing age are the most powerful predictors of AAA. Considering the higher prevalence of hypertension, it is surprising that the prevalence of AAA among African-American men is 39% less than white men. The risk of rupture is independently associated with female gender, large initial aneurysm diameter, lower forced expiratory volume in the first second, current smoking, and higher mean blood pressure. Inflammation rather than atherosclerosis may be essential to the development of AAA. Treatment is directed at smoking cessation and control of blood pressure and lipids. Beta blockers (propranolol) have not been shown to modify aneurysm growth rates, but drop out rates in the studies have been high. Antibiotics do show a modest benefit. Surgery is generally performed when the aneurysm exceeds 5.5 cm in men. For women, an AAA size between 4.5 cm and 5.0 cm is recommended for elective repair.