Current drug targets. Cardiovascular & haematological disorders最新文献_第9页

Endothelial dysfunction and coronary artery spasm. 内皮功能障碍和冠状动脉痉挛。

Current drug targets. Cardiovascular & haematological disorders Pub Date : 2004-03-01 DOI: 10.2174/1568006043481301

Hiroaki Kawano, Hisao Ogawa

引用次数: 25

Collagen cross-link breakers: a beginning of a new era in the treatment of cardiovascular changes associated with aging, diabetes, and hypertension. 胶原交联抑制剂:与衰老、糖尿病和高血压相关的心血管变化治疗新时代的开始

Current drug targets. Cardiovascular & haematological disorders Pub Date : 2004-03-01 DOI: 10.2174/1568006043481347

Dinko Susic, Jasmina Varagic, Jwari Ahn, Edward D Frohlich

{"title":"Collagen cross-link breakers: a beginning of a new era in the treatment of cardiovascular changes associated with aging, diabetes, and hypertension.","authors":"Dinko Susic, Jasmina Varagic, Jwari Ahn, Edward D Frohlich","doi":"10.2174/1568006043481347","DOIUrl":"https://doi.org/10.2174/1568006043481347","url":null,"abstract":"Aging, diabetes, and hypertension are conditions in which arterial and myocardial stiffness is increased. Increased arterial stiffness is manifested by an increased systolic arterial pressure, pulse pressure and pulse wave velocity, whereas increased myocardial stiffness is manifested by impaired left ventricular diastolic filling. Moreover, increased arterial stiffness increases cardiac workload, further aggravating already existing adverse changes in left ventricular structure and function. Indeed, studies in human beings have clearly shown that increased cardiovascular stiffness is a reliable predictor of cardiovascular morbidity and mortality. Increased cardiovascular stiffness is usually attributed to the development of fibrosis (i.e., accumulation of collagen). It has also been recognized that the increased cardiac and vascular stiffness may be due to increased collagen cross-linking due to the formation of advanced glycosylation end-products (AGEs). In agreement with this notion is the finding that an inhibitor of AGEs formation improves vascular stiffness in diabetic rats. More recently, cross-link breakers have been developed, and the beneficial effects of one such agent (ALT-711) have been shown in experimental and clinical settings. This report briefly summarizes age related changes in cardiovascular structure and function and describes results of experimental and clinical studies involving collagen cross-link breakers.","PeriodicalId":84523,"journal":{"name":"Current drug targets. Cardiovascular & haematological disorders","volume":" ","pages":"97-101"},"PeriodicalIF":0.0,"publicationDate":"2004-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568006043481347","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40851230","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: 40

Molecular mechanisms of impaired endothelial function associated with insulin resistance. 内皮功能受损与胰岛素抵抗相关的分子机制。

Current drug targets. Cardiovascular & haematological disorders Pub Date : 2004-03-01 DOI: 10.2174/1568006043481248

Kazuya Shinozaki, Atsunori Kashiwagi, Masahiro Masada, Tomio Okamura

{"title":"Molecular mechanisms of impaired endothelial function associated with insulin resistance.","authors":"Kazuya Shinozaki, Atsunori Kashiwagi, Masahiro Masada, Tomio Okamura","doi":"10.2174/1568006043481248","DOIUrl":"https://doi.org/10.2174/1568006043481248","url":null,"abstract":"Dysfunction of the endothelium in large- and medium-sized arteries plays a central role in atherogenesis. The insulin resistance syndrome encompasses more than a subnormal response to insulin-mediated glucose disposal. Patients with this syndrome also frequently display elevated blood pressure, hyperlipidemia, and dysfibinolysis, even without any clinically manifested alteration in plasma glucose concentrations. Of note endothelial dysfunction and atherosclerosis also have been demonstrated in patients with hypertension, which is one of the features of the syndrome of insulin resistance. Insulin-induced vasodilation, which is mediated by the release of nitric oxide (NO) release, is impaired in obese individuals who display insulin resistance. Although it is tempting to speculate that loss of endothelium-dependent vasodilation and increased vasoconstriction might be etiological factors of elevated blood pressure, the factors contributing to NO-mediated endothelial dysfunction in the insulin-resistant state are not fully defined. Experimental evidences suggest that (6R)-5,6,7,8-tetrahydrobiopterin (BH(4)), the natural and essential cofactor of NO synthases (NOS), plays a crucial role not only in increasing the rate of NO generation by NOS but also in controlling the formation of superoxide anion (O(2)(-)) in the endothelial cells. Under insulin-resistant conditions where BH(4) levels are suboptimal, in addition to a reduced synthesis of NO, an accelerated inactivation of NO by O(2)(-) within the vascular wall was observed. Furthermore, oral supplementation of BH(4) restored endothelial function and relieved oxidative tissue damage, through activation of eNOS in the aorta of insulin-resistant rats. These results indicate that abnormal pteridine metabolism contributes to causing endothelial dysfunction and the enhancement of vascular oxidative stress in the insulin-resistant state.","PeriodicalId":84523,"journal":{"name":"Current drug targets. Cardiovascular & haematological disorders","volume":" ","pages":"1-11"},"PeriodicalIF":0.0,"publicationDate":"2004-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568006043481248","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40851224","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: 45

Microglia: neuroprotective and neurotrophic cells in the central nervous system. 小胶质细胞:中枢神经系统中的神经保护细胞和神经营养细胞。

Current drug targets. Cardiovascular & haematological disorders Pub Date : 2004-03-01 DOI: 10.2174/1568006043481284

Kazuyuki Nakajima, Shinichi Kohsaka

{"title":"Microglia: neuroprotective and neurotrophic cells in the central nervous system.","authors":"Kazuyuki Nakajima, Shinichi Kohsaka","doi":"10.2174/1568006043481284","DOIUrl":"https://doi.org/10.2174/1568006043481284","url":null,"abstract":"Microglia are currently accepted as sensor cells in the central nervous system that respond to injury and brain disease. The main function of microglia is believed to be brain defense, as they are known to scavenge invading microorganisms and dead cells, and also to act as immune or immunoeffector cells. However, microglia are also thought to contribute to the onset of or to exacerbate neuronal degeneration and/or inflammation in many brain diseases by producing deleterious factors including superoxide anions, nitric oxide and inflammatory cytokines. Nonetheless, microglia have also been shown to act neuroprotectively by eliminating excess excitotoxins in the extracellular space. Moreover, there is accumulating evidence that microglia produce neurotrophic and/or neuroprotective molecules; in particular, it has been suggested that they promote neuronal survival in cases of brain injury. In general, the question of whether microglia act as neurotoxic cells or as neuroprotective cells in vivo has gained much recent attention. In this paper, we provide a review of findings indicating that the microglia are basically neurotrophic/neuroprotective cells in the nervous system. In addition, the mechanism by which neurotrophic microglia become oriented to a neurotoxic state is discussed.","PeriodicalId":84523,"journal":{"name":"Current drug targets. Cardiovascular & haematological disorders","volume":" ","pages":"65-84"},"PeriodicalIF":0.0,"publicationDate":"2004-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568006043481284","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40851229","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: 256

Current understanding of in-stent restenosis and the potential benefit of drug eluting stents. 目前对支架内再狭窄的认识和药物洗脱支架的潜在益处。

Current drug targets. Cardiovascular & haematological disorders Pub Date : 2004-03-01 DOI: 10.2174/1568006043481293

M Froeschl, S Olsen, X Ma, E R O'Brien

引用次数: 21

Endothelial dysfunction and coronary atherosclerosis. 内皮功能障碍和冠状动脉粥样硬化。

Current drug targets. Cardiovascular & haematological disorders Pub Date : 2004-03-01 DOI: 10.2174/1568006043481257

Shiro Kitamoto, Kensuke Egashira

{"title":"Endothelial dysfunction and coronary atherosclerosis.","authors":"Shiro Kitamoto, Kensuke Egashira","doi":"10.2174/1568006043481257","DOIUrl":"https://doi.org/10.2174/1568006043481257","url":null,"abstract":"Increasing evidence has revealed that endothelial cells play an important role in the pathogenesis of development and progression of atherosclerosis. Endothelial dysfunction induces disruption of the balance between vasoconstrictive factors and vasodilatory factors secreted from endothelial cells. Among these factors, NO and angiotensin II are especially important factors, and have been shown to exert various direct effects on the endothelial functions that are closely related to the pathogenesis of atherosclerosis. Endothelial dysfunction induces decreased NO bioactivity and increased angiotensin II expression, which increase oxidative stress and expression of adhesion molecules, cytokines, and chemokines. These conditions mediate inflammation, proliferation, and thrombogenesis in vessel wall and promote atherosclerotic lesions. On the other hand, therapies that improve endothelial dysfunction, such as administration of HMG-CoA reductase inhibitors or angiotensin converting inhibitors, have been demonstrated to reduce cardiovascular events and strokes. In this article, we focus on NO and angiotensin II and describe their roles in the pathogenesis of atherosclerosis.","PeriodicalId":84523,"journal":{"name":"Current drug targets. Cardiovascular & haematological disorders","volume":" ","pages":"13-22"},"PeriodicalIF":0.0,"publicationDate":"2004-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568006043481257","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40851225","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: 15

Preface [Hot topic: Insulin Resistance and Impaired Coronary Endothelial Function (Guest Editor: Teruo Inoue)] 【热门话题:胰岛素抵抗与冠状动脉内皮功能受损(特邀编辑:Teruo Inoue)】

Current drug targets. Cardiovascular & haematological disorders Pub Date : 2004-02-29 DOI: 10.2174/1568006043481338

Teruo Inoue

引用次数: 0

Re-establishment of a normal apoptotic process as a therapeutic approach in B-CLL. 重建正常凋亡过程作为治疗B-CLL的途径。

Current drug targets. Cardiovascular & haematological disorders Pub Date : 2003-12-01 DOI: 10.2174/1568006033481384

Jean-Pierre Kolb, Catherine Kern, Claire Quiney, Viviana Roman, Christian Billard

{"title":"Re-establishment of a normal apoptotic process as a therapeutic approach in B-CLL.","authors":"Jean-Pierre Kolb, Catherine Kern, Claire Quiney, Viviana Roman, Christian Billard","doi":"10.2174/1568006033481384","DOIUrl":"https://doi.org/10.2174/1568006033481384","url":null,"abstract":"Even though the capacity of B-CLL leukemic cells to proliferate has been underestimated until recently, the accumulation of tumor cells in patients mostly results from a defect in the apoptotic program. Several mechanisms can account for this deficient cell death pathway. These include overexpression of anti-apoptotic molecules such as members of the Bcl-2 family, which control the opening of the mitochondrial transition permeability pore, and of the IAP (inhibitors of apoptosis) family, which inhibit the activity of caspases. The latter is also suppressed by nitric oxide (NO) released through an inducible NO synthase present in the leukemic cells. The activity of the receptors with a death domain (Fas, TRAIL) is impaired, thus contributing to the resistance to spontaneous and/or drug-induced apoptosis. Interferons as well as several cytokines and angiogenic factors are also involved in the failure of programmed cell death, either by providing efficient signals for survival (BAFF) or by counteracting the apoptotic process. A better knowledge of the mechanisms of survival and escape from apoptosis of B-CLL cells has led to the proposal of new drugs that selectively interfere at the different steps of these cascades. Their study is complicated by the lack of suitable cell lines and pre-clinical models. Nevertheless, some of these chemotherapeutic agents appear to be promising, provided they are correctly targeted to the leukemic cells.","PeriodicalId":84523,"journal":{"name":"Current drug targets. Cardiovascular & haematological disorders","volume":"3 4","pages":"261-86"},"PeriodicalIF":0.0,"publicationDate":"2003-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24131081","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: 45

An update on new anticoagulants. 新型抗凝血剂的最新进展。

Current drug targets. Cardiovascular & haematological disorders Pub Date : 2003-12-01 DOI: 10.2174/1568006033481366

Lori-Ann Linkins, Jeffrey I Weitz

引用次数: 2

Selective protein kinase C inhibitors and their applications. 选择性蛋白激酶C抑制剂及其应用。

Current drug targets. Cardiovascular & haematological disorders Pub Date : 2003-12-01 DOI: 10.2174/1568006033481375

Garry X Shen

{"title":"Selective protein kinase C inhibitors and their applications.","authors":"Garry X Shen","doi":"10.2174/1568006033481375","DOIUrl":"https://doi.org/10.2174/1568006033481375","url":null,"abstract":"Protein kinase C (PKC) represents a family of phospholipid-dependent serine/threonine kinase. PKC was detected in almost all types of cells and tissues in the body. The activation of PKC is involved in the signal regulation of many physiological and pathological processes. PKC has multiple isoforms (alpha, betaI, betaII, gamma delta, epsilon, eta, theta, xi, iota and micro). PKC-mediated cellular processes are tissue- and isoform-specific. Investigations on selective or isoform-specific PKC inhibitors have attracted great attention during last two decades. Recent studies demonstrated that LY333531, a PKC-beta-specific inhibitor, reduced the development of diabetic vascular complications in animal models and prevented hyperglycemia-induced impairment of endothelial-dependent vasodilation in healthy subjects. Results from phase I clinical trial suggested low risk of the inhibitor. Phase III clinical trials on the safety and the preventive effects of the PKC-beta-specific inhibitor on diabetic complications are under progress. The efficacy of ISSI-3521, a PKC-alpha antisense inhibitor, on slowing the growth and metastasis of solid tumors is currently being examined in clinical trials. Partial responses in the prevention of the progress of malignancies were found in early phases of clinical trials for UCN-01 and CGP41251, two partially isoform-specific PKC inhibitors. Recent findings suggest that isoform-specific PKC inhibitors are potentially beneficial to the prevention or treatment of some common diseases, including cancers and diabetic vascular complications. Safety and efficacy studies of the PKC inhibitors will be required through large-scale long-term clinical trials.","PeriodicalId":84523,"journal":{"name":"Current drug targets. Cardiovascular & haematological disorders","volume":"3 4","pages":"301-7"},"PeriodicalIF":0.0,"publicationDate":"2003-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568006033481375","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24131083","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: 54