Current drug targets. Cardiovascular & haematological disorders最新文献_第4页

B cell tolerance: lessons from transplantation. B细胞耐受性:移植的教训。

Current drug targets. Cardiovascular & haematological disorders Pub Date : 2005-06-01 DOI: 10.2174/1568006054064771

Marilia Cascalho

引用次数: 5

Targeting antibody-mediated rejection in the setting of ABO-incompatible infant heart transplantation: graft accommodation vs. B cell tolerance. abo血型不相容婴儿心脏移植中靶向抗体介导的排斥反应:移植物调节与B细胞耐受

Current drug targets. Cardiovascular & haematological disorders Pub Date : 2005-06-01 DOI: 10.2174/1568006054064762

Lori J West

{"title":"Targeting antibody-mediated rejection in the setting of ABO-incompatible infant heart transplantation: graft accommodation vs. B cell tolerance.","authors":"Lori J West","doi":"10.2174/1568006054064762","DOIUrl":"https://doi.org/10.2174/1568006054064762","url":null,"abstract":"In order for ABO-incompatible organ transplantation to be performed successfully, the antibody response must be targeted. Aggressive strategies are usually required both to remove pre-existing antibodies directed at donor A/B antigens and to suppress further production of antibodies. If this can be accomplished in the short-term, graft accommodation of ABO-incompatible transplants may develop upon eventual re-accumulation of antibodies as the graft acquires resistance to antibody-mediated damage. In contrast to mature individuals, very young infants lack isohemagglutinins due to a natural lag in development of immunity to T cell-independent polysaccharide antigens. This delay in maturation permits a window of safety during which infants can receive ABO-incompatible grafts without the requirement for aggressive immunosuppressive strategies. We have recently demonstrated that ABO-incompatible heart transplantation performed during this stage of immaturity is followed by the spontaneous development of donor-specific B cell tolerance rather than graft accommodation, and that tolerance in this setting occurs by a cellular mechanism of antigen-specific B cell elimination. This finding is strikingly similar to the original descriptions of neonatal T cell tolerance in mice. Our data provide compelling justification that every effort should be made to include juvenile recipients routinely as subjects in tolerance research. Through understanding the mechanisms underlying tolerance in this setting, as with murine models of neonatal tolerance originally described by Medawar and colleagues, it may be possible to expand the potential applications of tolerance strategies to older patient populations.","PeriodicalId":84523,"journal":{"name":"Current drug targets. Cardiovascular & haematological disorders","volume":"5 3","pages":"223-32"},"PeriodicalIF":0.0,"publicationDate":"2005-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568006054064762","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24862394","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: 31

Pathological features of antibody-mediated rejection. 抗体介导的排斥反应的病理特征。

Current drug targets. Cardiovascular & haematological disorders Pub Date : 2005-06-01 DOI: 10.2174/1568006054064744

Akira Shimizu, Robert B Colvin

{"title":"Pathological features of antibody-mediated rejection.","authors":"Akira Shimizu, Robert B Colvin","doi":"10.2174/1568006054064744","DOIUrl":"https://doi.org/10.2174/1568006054064744","url":null,"abstract":"Although cell-mediated rejection has remained the most common form of graft rejection after organ transplantation, antibody-mediated rejection has recently gained much significance in clinical transplantation. New evidence points to an antibody-mediated rejection contributing not only to hyperacute and acute but also to chronic allograft rejection. In addition, in discordant xenotransplantation, severe forms of antibody-mediated rejection, including hyperacute rejection and acute humoral xenograft rejection, represent major immunological barriers to successful xenotransplantation. Antibody-mediated rejection in both allotransplantation and xenotransplantation typically does not respond to conventional anti-rejection therapy, so it has recently been recognized as a major cause of graft loss. Histopathology remains the most definitive and reliable tool for the diagnosis of graft rejection in both allografts and xenografts. In this review, we discuss the concept that microvascular injury is a characteristic feature of antibody-mediated rejection that develops in hyperacute, acute and chronic antibody-mediated rejection in both allografts and discordant xenografts as well as in kidney and heart grafts. We also review work indicating that endothelial cell activation and endothelial cell death in the microvasculature can contribute to ultimate graft loss by triggering capillary destruction, interstitial hemorrhage, and platelet-rich microthrombi in hyperacute and acute antibody-mediated rejection as well as with the formation and progression of fibrotic scars in chronic antibody-mediated rejection.","PeriodicalId":84523,"journal":{"name":"Current drug targets. Cardiovascular & haematological disorders","volume":"5 3","pages":"199-214"},"PeriodicalIF":0.0,"publicationDate":"2005-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568006054064744","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24862392","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: 27

Beyond antibody-mediated rejection: hyperacute lung rejection as a paradigm for dysregulated inflammation. 超越抗体介导的排斥反应:超急性肺排斥反应作为失调炎症的范例。

Current drug targets. Cardiovascular & haematological disorders Pub Date : 2005-06-01 DOI: 10.2174/1568006054064753

Bao H Nguyen, Egon Zwets, Carsten Schroeder, Richard N Pierson, Agnes M Azimzadeh

引用次数: 17

Editorial [Hot Topic:Fighting Antibody Mediated Rejection (Guest Editor: Robert Zhong )] 社论[热点话题:抗抗体介导的排斥反应(特邀编辑:Robert Zhong)]

Current drug targets. Cardiovascular & haematological disorders Pub Date : 2005-05-31 DOI: 10.2174/1568006054064780

R. Zhong

引用次数: 0

Statin-induced vascular smooth muscle cell apoptosis: a possible role in the prevention of restenosis? 他汀类药物诱导的血管平滑肌细胞凋亡:在预防再狭窄中的可能作用?

Current drug targets. Cardiovascular & haematological disorders Pub Date : 2005-04-01 DOI: 10.2174/1568006043586134

Wolfgang Erl

{"title":"Statin-induced vascular smooth muscle cell apoptosis: a possible role in the prevention of restenosis?","authors":"Wolfgang Erl","doi":"10.2174/1568006043586134","DOIUrl":"https://doi.org/10.2174/1568006043586134","url":null,"abstract":"Growing evidence suggests that statins are more than simple lipid-lowering drugs. The so called pleiotropic effects of statins include multiple actions on cells of the vasculature. A large number of studies have confirmed that these compounds exert beneficial effects by mechanisms unrelated to cholesterol metabolism. For example, statins have been shown to inhibit the migration and proliferation of vascular smooth muscle cells (VSMC), and to induce apoptosis in this cell type. It is not yet clear if the induction of apoptosis in VSMC by statins is beneficial or detrimental. In the context of post-angioplasty restenosis, recurrent plaque growth after intervention, the inhibition of neointimal proliferation as well as a reduction of neointimal cell numbers by apoptosis is appealing. Multiple animal studies and clinical trials have therefore been undertaken to investigate effects of statin treatment on the development of restenosis, with very controversial results. Conversely, in advanced atherosclerotic lesions VSMC in the intima may stabilize the plaque and prevent plaque rupture by synthesizing collagen. VSMC in media adjacent to plaque areas or restenotic lesions should not be exposed to apoptosis promoting agents. In this context, recent evidence suggests that pravastatin protects such lesions by inhibiting inflammation and macrophage activation Our recent findings together with observations from other groups suggest that neointima cells are more sensitive to the induction of apoptosis than media VSMC. Importantly, statins were found to preferentially induce apoptosis in neointimal VSMC in our study. The purpose of the present review is to summarize statin effects on proliferation and apoptosis in VSMC in vitro and in vivo. Furthermore, the development of drug-coated stents may help to deliver high local doses of statins to enhance their effectiveness in the treatment of post-angioplasty restenosis.","PeriodicalId":84523,"journal":{"name":"Current drug targets. Cardiovascular & haematological disorders","volume":"5 2","pages":"135-44"},"PeriodicalIF":0.0,"publicationDate":"2005-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568006043586134","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25077550","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: 47

Statins: effects beyond cholesterol lowering. 他汀类药物:除降低胆固醇外的作用。

Current drug targets. Cardiovascular & haematological disorders Pub Date : 2005-04-01 DOI: 10.2174/1568006043586215

Garry X Shen

引用次数: 2

Statins and thrombin. 他汀类药物和凝血酶。

Current drug targets. Cardiovascular & haematological disorders Pub Date : 2005-04-01 DOI: 10.2174/1568006043586189

J W Fenton, D V Brezniak, F A Ofosu, G X Shen, J R Jacobson, J G N Garcia

{"title":"Statins and thrombin.","authors":"J W Fenton, D V Brezniak, F A Ofosu, G X Shen, J R Jacobson, J G N Garcia","doi":"10.2174/1568006043586189","DOIUrl":"https://doi.org/10.2174/1568006043586189","url":null,"abstract":"L-Mevalonic acid is the distant precursor of cholesterol, in contrast to cholesterol, L-mevalonic acid, its distant precursor gives rise to farnesyl and geranylgeranyl pyrophosphates in relatively few metabolic steps. These isoprenyl pyrophophates covalently conjugate with specific G-proteins and serve as membrane anchors enabling them to carry out their function. Although farnesyl-proteins may participate in signal transduction, geranylgeranyl-proteins (e.g., Rho GTP binding proteins) are well known to downregulate signaling pathways by inhibiting L-mevalonic acid synthesis. Such inhibitors include 3-hydroxy-3-methylglutaryl CoA reductase inhibitors, drugs (statins) and isoprenoids of dietary origins, where Rho protein activation appears to be necessary for cellular-mediated thrombin generation. Thrombin and other proteases (e.g., coagulation factor Xa, tryptase) upregulate protease-activated receptor (PAR) synthesis and PAR activation promotes synthesis and expression of other proteins [e.g., tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1)]. With the PAR-1 activating peptide SSFLRNP, we found that either cerivastatin or atorvastatin mitigated platelet stimulation in a time- and dose-dependent manner, as predicted if a statin-mediated Rho pathway is required. We also found that simvastatin decreased prothrombin fragments F1+2 in plasma from type 2 diabetics, demonstrating that statins downregulate thrombin generation. Thus, independent of cholesterol, statins and dietary isoprenoids behave as inhibitors of TF-dependent thrombin generation. Because thrombin has multiple physiological functions, the 20 pleiotropic effects reported for statins may reflect a common mechanism for downregulation of thrombin-mediated events, in particular at the cellular level.","PeriodicalId":84523,"journal":{"name":"Current drug targets. Cardiovascular & haematological disorders","volume":"5 2","pages":"115-20"},"PeriodicalIF":0.0,"publicationDate":"2005-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568006043586189","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25077547","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: 21

Mechanisms for antiplatelet action of statins. 他汀类药物抗血小板作用的机制。

Current drug targets. Cardiovascular & haematological disorders Pub Date : 2005-04-01 DOI: 10.2174/1568006043586161

Luca Puccetti, Anna Laura Pasqui, Alberto Auteri, Fulvio Bruni

{"title":"Mechanisms for antiplatelet action of statins.","authors":"Luca Puccetti, Anna Laura Pasqui, Alberto Auteri, Fulvio Bruni","doi":"10.2174/1568006043586161","DOIUrl":"https://doi.org/10.2174/1568006043586161","url":null,"abstract":"Hydroxymethyl-glutaryl coenzyme A reductase inhibitors (statins) offer important benefits for the large populations of individuals at high risk for coronary heart and cerebrovascular disease. the overall clinical benefits observed with statin therapy appear to be greater than what might be expected from changes in lipid profile alone, suggesting that the beneficial effects of such drugs may extend beyond their effects on serum cholesterol. Platelet hyperactivity is a key step in atherothrombosis and experimental data suggest that statins could exert an antiplatelet effect which could be involved in their protective action. In the present review we report of the major studies in humans showing the effect of statins on platelets, especially by the more sensitive methods to explore platelet function such as cytofluorymetric detection of specific proteins. Moreover we describe the putative mechanisms involved in platelet deactivation with particular regard to the effects related to cholesterol reduction or beyond lipid-lowering. Indeed, data from several studies suggest some differences among compounds in terms of timing of action by modulation of several activating pathways which could take part either in the early, cholesterol-lowering independent, effects in the acute phase of vascular disease or during chronic treatment.","PeriodicalId":84523,"journal":{"name":"Current drug targets. Cardiovascular & haematological disorders","volume":"5 2","pages":"121-6"},"PeriodicalIF":0.0,"publicationDate":"2005-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568006043586161","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25077548","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: 24

Cholesterol-independent effects of statins in inflammation, immunomodulation and atherosclerosis. 他汀类药物在炎症、免疫调节和动脉粥样硬化中的胆固醇非依赖性作用。

Current drug targets. Cardiovascular & haematological disorders Pub Date : 2005-04-01 DOI: 10.2174/1568006043586198

Claire Arnaud, Niels R Veillard, François Mach

引用次数: 53