Current drug targets. Cardiovascular & haematological disorders最新文献_第10页

Leukocyte recruitment to atherosclerotic lesions, a complex web of dynamic cellular and molecular interactions. 白细胞募集到动脉粥样硬化病变，一个复杂的动态细胞和分子相互作用的网络。

Current drug targets. Cardiovascular & haematological disorders Pub Date : 2003-12-01 DOI: 10.2174/1568006033481357

Einar E Eriksson

{"title":"Leukocyte recruitment to atherosclerotic lesions, a complex web of dynamic cellular and molecular interactions.","authors":"Einar E Eriksson","doi":"10.2174/1568006033481357","DOIUrl":"https://doi.org/10.2174/1568006033481357","url":null,"abstract":"The accumulation of leukocytes in atherosclerotic lesions is of fundamental importance in the development of atherosclerosis. Consequently, the adhesive and signaling mechanisms responsible for leukocyte invasion in the arterial wall have been intensively studied as potential targets for therapeutic intervention. During recent years, it has become increasingly clear that leukocyte recruitment in atherosclerosis is mediated by a complex series of cellular and molecular interactions that in many ways resemble those that take place in tissue inflammation. However, certain aspects of leukocyte recruitment in atherosclerosis are specific for this disease and present themselves as interesting drug targets. This review summarizes the current knowledge about the mechanisms that guide the extravasation of leukocytes to inflamed tissues, with special focus on atherosclerotic lesions. Moreover, novel experimental techniques are described, techniques that allow for the study of dynamic events taking place in atherosclerosis and that have provided interesting insights into lesion pathology. The data reviewed contribute to the understanding of atherosclerosis, and may help in the development of treatment strategies for a disease that is a major contributor to morbidity and mortality in the western world today.","PeriodicalId":84523,"journal":{"name":"Current drug targets. Cardiovascular & haematological disorders","volume":"3 4","pages":"309-25"},"PeriodicalIF":0.0,"publicationDate":"2003-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24131084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 19

Drug induced QT prolongation: lessons from congenital and acquired long QT syndromes. 药物引起的QT间期延长:先天性和后天性长QT综合征的经验教训。

Current drug targets. Cardiovascular & haematological disorders Pub Date : 2003-12-01 DOI: 10.2174/1568006033481393

Bruce D Walker, Andrew D Krahn, George J Klein, Allan C Skanes, Raymond Yee

引用次数: 6

The role of neuropeptides and neurohormones in neurogenic cardiac arrhythmias. 神经肽和神经激素在神经性心律失常中的作用。

Current drug targets. Cardiovascular & haematological disorders Pub Date : 2003-09-01 DOI: 10.2174/1568006033481456

T M Saleh

{"title":"The role of neuropeptides and neurohormones in neurogenic cardiac arrhythmias.","authors":"T M Saleh","doi":"10.2174/1568006033481456","DOIUrl":"https://doi.org/10.2174/1568006033481456","url":null,"abstract":"The functional significance of neuropeptides and neurohormones throughout the neuroaxis has been the focus of considerable research over the past 25 years. These \"gut peptides\" or \"reproductive hormones\" have been localized within nuclei responsible for the relay of visceral afferent information to the forebrain. The presence of peptides and hormones along the gut- or heart-brain continuum suggests that these neurochemicals do more than modulate the visceral processes of digestion and reproduction respectively. Numerous studies have shown that the exogenous administration of these neurochemicals directly into visceral afferent nuclei significantly alters blood pressure, heart rate, autonomic tone and the sensitivity of the baroreceptor reflex (an index of sympatho-vagal balance). A strong inverse correlation has been demonstrated between the sensitivity of the baroreceptor reflex and susceptibility to lethal cardiac arrhythmias which lead ultimately to sudden cardiac death. The differential effects of various neurochemicals on the sensitivity of the baroreceptor reflex suggests that some neurochemicals may act as preventatives while others may actually contribute to the pathogenesis of neurogenic cardiac arrhythmias. Hormones such as estrogen, in addition to their neuroprotective properties, may also play a role in modulating the cardiovascular consequences to neurogenic pathologies including stroke and epilepsy. This review will summarize the evidence available which suggests that neuropeptides and neurohormones can alter both neurogenic as well as visceral pathology-induced changes in autonomic function resulting in an increased risk of sudden cardiac death.","PeriodicalId":84523,"journal":{"name":"Current drug targets. Cardiovascular & haematological disorders","volume":"3 3","pages":"240-53"},"PeriodicalIF":0.0,"publicationDate":"2003-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22490420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 9

Molecular diversity of the developing and adult myocardium: implications for tissue targeting. 发育和成人心肌的分子多样性:组织靶向的意义。

Current drug targets. Cardiovascular & haematological disorders Pub Date : 2003-09-01 DOI: 10.2174/1568006033481429

María del Pilar de Castro, Lourdes Acosta, Jorge N Domínguez, Amelia Aránega, Diego Franco

{"title":"Molecular diversity of the developing and adult myocardium: implications for tissue targeting.","authors":"María del Pilar de Castro, Lourdes Acosta, Jorge N Domínguez, Amelia Aránega, Diego Franco","doi":"10.2174/1568006033481429","DOIUrl":"https://doi.org/10.2174/1568006033481429","url":null,"abstract":"The heart is the first functional embryonic organ. During embryogenesis the development of the heart and its vasculature is a complex process that give rise to the formation of four-chambered heart with a synchronously contraction, from a single tubular heart with a peristaltic contraction. The spectacular progress of modern developmental biology has marked the beginning of a new era in embryology. Over the last years, several families of genes with restricted cardiac expression have been identified including genes such as those encoding for tissue-specific transcription factors, contractile proteins, as well as, more recently, ion channels. In this review, we illustrate the heterogeneity of the developing and adult myocardium in mice. Looking at the expression profile of transcription factors and contractile proteins, it can be seen that the tubular heart is patterned along the three embryonic axes, antero/posterior, dorso/ventral and left/right, besides having several genes that are expressed homogeneously within the entire myocardium. In the embryonic heart, two new types of pattern arise, chamber-specific and systemic/pulmonary gene expression, while within the foetal and adult heart, a wider heterogeneity is observed, not only between the working myocardium and the specialized cardiac conduction system but also within distinct myocardial chambers, specially in the atrial components. Such heterogeneity is also observed if one looks at the electrophysiological characteristics of the developing myocardium and their underlying molecular components. Several evidences support the notion that the distinct expression profiles observed in mice can be extrapolated to humans. Thus, these data reveal that the molecular diversity of the myocardium should be taken into account on the design of drug targets as well as on gene and cell therapy approaches.","PeriodicalId":84523,"journal":{"name":"Current drug targets. Cardiovascular & haematological disorders","volume":"3 3","pages":"227-39"},"PeriodicalIF":0.0,"publicationDate":"2003-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22490419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 7

Novel immunotherapeutic strategies for invasive fungal disease. 侵袭性真菌疾病的新免疫治疗策略。

Current drug targets. Cardiovascular & haematological disorders Pub Date : 2003-09-01 DOI: 10.2174/1568006033481438

A B van Spriel

{"title":"Novel immunotherapeutic strategies for invasive fungal disease.","authors":"A B van Spriel","doi":"10.2174/1568006033481438","DOIUrl":"https://doi.org/10.2174/1568006033481438","url":null,"abstract":"Infectious diseases still represent a major cause of mortality in man. Failure of the immune system to eradicate pathogens may result in serious invasive infections. Increasing numbers of immunocompromised patients, ineffective treatment and the emergence of drug-resistant pathogens represent the underlying problems. The focus of this review is on the pathogenesis of systemic fungal disease and the development of novel immunotherapeutic approaches. A comprehensive understanding of host-pathogen interactions is required for manipulation of immune responses to direct anti-fungal immunity. The potential of growth factor- and antibody-based therapeutics for invasive fungal disease are discussed. Recent advances in antibody technology may provide new strategies for developing antibody-based anti-fungal therapies. Development of fungal disease is related primarily to impaired host defense mechanisms, which emphasizes the importance of immunorestorative therapy in immunocompromised individuals. Controlled comparative clinical research is needed to evaluate the efficacy of novel immunotherapies, which provide prospects for the future management of invasive fungal disease.","PeriodicalId":84523,"journal":{"name":"Current drug targets. Cardiovascular & haematological disorders","volume":"3 3","pages":"209-17"},"PeriodicalIF":0.0,"publicationDate":"2003-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22491036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Hypoxia-inducible factor-1: a molecular hint of physiological changes in the carotid body during long-term hypoxemia? 低氧诱导因子-1:长期低氧血症时颈动脉体生理变化的分子提示?

Current drug targets. Cardiovascular & haematological disorders Pub Date : 2003-09-01 DOI: 10.2174/1568006033481447

Man-Lung Fung

{"title":"Hypoxia-inducible factor-1: a molecular hint of physiological changes in the carotid body during long-term hypoxemia?","authors":"Man-Lung Fung","doi":"10.2174/1568006033481447","DOIUrl":"https://doi.org/10.2174/1568006033481447","url":null,"abstract":"The aims of this review are to describe recent data focusing on the anatomical, functional and molecular changes of the carotid body during chronic hypoxemia, and to summarize current views in the literature relevant to the topic. The carotid body is the major peripheral sensor for detecting chemicals in the arterial blood. In acute hypoxia, carotid chemoreceptors transduce the signal to the brain for triggering reflexive responses of the cardiopulmonary system. The carotid body enlarges and changes its hypoxic sensitivity in humans and animals living at high altitude or subject to long-term hypoxemia associated with chronic cardiopulmonary diseases or hematological disorders. Recently, a surge of new evidence suggests that a heterodimeric transcriptional factor directly induced by severe tissue or cellular hypoxia, namely hypoxia-inducible factor-1 (HIF-1), is a key controller for the transcriptional regulation of the gene expression of a spectrum of proteins for the cellular response to hypoxia. These proteins, such as endothelin-1, type II nitric oxide synthase and vascular endothelial growth factor, play important physiological roles in the control of vascular tone and angiogenesis. In the carotid body, chronic hypoxemia induces remodeling of the vasculature, stimulates proliferation of the chemosensitive cells, and changes their excitability and sensitivity to chemical signals. In addition, HIF-1-targeted genes are expressed in the carotid body and the expression is modulated by chronic hypoxemia, suggesting an active role for HIF-1 in moderate levels of hypoxic stress.","PeriodicalId":84523,"journal":{"name":"Current drug targets. Cardiovascular & haematological disorders","volume":"3 3","pages":"254-9"},"PeriodicalIF":0.0,"publicationDate":"2003-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22490421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 17

Coronary atherosclerotic disease burden: an emerging endpoint in progression/regression studies using intravascular ultrasound. 冠状动脉粥样硬化疾病负担:血管内超声进展/倒退研究中的一个新终点。

Current drug targets. Cardiovascular & haematological disorders Pub Date : 2003-09-01 DOI: 10.2174/1568006033481401

Paul Schoenhagen, Steven E Nissen

引用次数: 36

The heme oxygenase system: its role in liver inflammation. 血红素加氧酶系统:在肝脏炎症中的作用。

Current drug targets. Cardiovascular & haematological disorders Pub Date : 2003-09-01 DOI: 10.2174/1568006033481410

Christian Wunder, Richard F Potter

{"title":"The heme oxygenase system: its role in liver inflammation.","authors":"Christian Wunder, Richard F Potter","doi":"10.2174/1568006033481410","DOIUrl":"https://doi.org/10.2174/1568006033481410","url":null,"abstract":"Heme Oxygenase is the rate-limiting enzyme in the degradation of heme into carbon monoxide (CO), iron and bilirubin. To date, three heme oxygenase isozymes have been identified: HO-1, HO-2 and HO-3. While HO-1 is structurally different from its counterparts, HO-2 and HO-3 are very similar (90% homology), with HO-3 being a poor heme catalyst. Of the three isozymes, HO-1 is believed to be the only inducible form. Constitutively expressed HO-2 has been identified in several organs including kidney and vascular smooth muscle, with the most abundant sources (and activity) being in the liver, brain, spleen and testes. Within the normal liver, HO-2 is constitutively expressed within hepatocytes, Kupffer cells, endothelial cells and Ito cells. Until recently, products of the HO reaction were regarded as potentially toxic waste destined only for excretion. However, this view is changing as evidence suggests that HO activity plays an important protective role against cellular stress during inflammatory diseases. Biliverdin is reduced to bilirubin, which has been shown to possess potent antioxidative properties. CO, which is produced in equimolar concentrations to biliverdin and ferrous iron during heme oxidation by HO, may function as a second messenger stimulating soluble guanylate cyclase (sGC) and regulating vascular tone in combination with the free radical gas NO. CO may also possess anti-inflammatory properties such as the capacity to inhibit platelet aggregation, or the expression of pro-inflammatory cytokines. Recently, it has been shown that CO regulates bile formation and bile flow. We review the functional role of HO in liver and the potential application of HO-1 in therapeutic approaches to the treatment of inflammation.","PeriodicalId":84523,"journal":{"name":"Current drug targets. Cardiovascular & haematological disorders","volume":"3 3","pages":"199-208"},"PeriodicalIF":0.0,"publicationDate":"2003-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22491035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 87

Observations on the use of the avian chorioallantoic membrane (CAM) model in investigations into angiogenesis. 禽类绒毛尿囊膜(CAM)模型在血管生成研究中的应用观察。

Current drug targets. Cardiovascular & haematological disorders Pub Date : 2003-06-01 DOI: 10.2174/1568006033481492

Mary Richardson, Gurmit Singh

{"title":"Observations on the use of the avian chorioallantoic membrane (CAM) model in investigations into angiogenesis.","authors":"Mary Richardson, Gurmit Singh","doi":"10.2174/1568006033481492","DOIUrl":"https://doi.org/10.2174/1568006033481492","url":null,"abstract":"The chorioallantoic membrane (CAM) is widely used as a model to examine angiogenesis, and anti-angiogenesis. Its advantages over mammalian systems include low cost, and ease of preparation, as well as the absence of a mature immune system. Although the use of this model presents a major opportunity to compare data generated in different laboratories, thereby expediting the evaluation of new drugs, angiogenic potential of cells and tissues, and body fluids, as well as to provide meaningful information concerning the molecular mechanisms involved, the wide range of methodologies used, especially in the quantification of the response, make any comparison essentially invalid. In this review, the major methodologies for all aspects of the use of the CAM in angiogenesis-related studies have been described. These include the source of the CAM, the methods for culture, and methods for evaluation of normal growth and of the response to an intervention. Methods for applying an intervention, the age for intervention and the duration of an intervention are documented. The structure and growth characteristics, the nature of possible responses to stimulation and inhibition of angiogenesis, and the complications of non-specific reactions have been examined. The need for a standardized approach to the use of the CAM model is obvious. One set of possible parameters is suggested.","PeriodicalId":84523,"journal":{"name":"Current drug targets. Cardiovascular & haematological disorders","volume":"3 2","pages":"155-85"},"PeriodicalIF":0.0,"publicationDate":"2003-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22403830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 84

Novel and emerging therapies in cardiology and haematology. 心脏病学和血液学的新疗法。

Current drug targets. Cardiovascular & haematological disorders Pub Date : 2003-06-01 DOI: 10.2174/1568006033481465

John E Pimanda, Harry C Lowe, Philip J Hogg, Colin N Chesterman, Levon M Khachigian

{"title":"Novel and emerging therapies in cardiology and haematology.","authors":"John E Pimanda, Harry C Lowe, Philip J Hogg, Colin N Chesterman, Levon M Khachigian","doi":"10.2174/1568006033481465","DOIUrl":"https://doi.org/10.2174/1568006033481465","url":null,"abstract":"Reviewing advances in cardiology and haematology together may appear at first sight to require some artificiality to make a satisfying fit. For two reasons, at least, this is not the case. Firstly, convergence in biology has become very clear over the past decade and this could not be better illustrated by the demonstration that the haemangioblast is the common progenitor of both haemapoietic stem cells and vascular endothelium. This opens the way to common (and differential) approaches to the manipulation of these cells, a field at present in its infancy. A second convergence is the common goal of understanding the processes resulting in haemostasis, thrombosis and vascular occlusion and the means for developing effective antithrombotics. This is exemplified by a number of agents either in use or in clinical trial as a result of haematological and cardiological collaboration. This collaboration is recognisable with the development, many years ago, of streptokinase and the use of aspirin in vascular disease and continues to this day with specific antiplatelet inhibitors and oral thrombin inhibitors as they become accepted into clinical use over the next few years. Here we review current advances in pharmacological treatments in cardiology and haematology, grouped primarily by disease process, focusing on novel and emerging therapies likely to be of importance in the future.","PeriodicalId":84523,"journal":{"name":"Current drug targets. Cardiovascular & haematological disorders","volume":"3 2","pages":"101-23"},"PeriodicalIF":0.0,"publicationDate":"2003-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22404477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1