Abstract:
:Heme oxygenase-1 (HO-1) metabolizes heme to generate carbon monoxide (CO), biliverdin, and iron. Biliverdin is subsequently metabolized to bilirubin by biliverdin reductase. HO-1 has recently emerged as a promising therapeutic target in the treatment of vascular disease. Pharmacological induction or gene transfer of HO-1 ameliorates vascular dysfunction in animal models of atherosclerosis, post-angioplasty restenosis, vein graft stenosis, thrombosis, myocardial infarction, and hypertension, while inhibition of HO-1 activity or gene deletion exacerbates these disorders. The vasoprotection afforded by HO-1 is largely attributable to its end products: CO and the bile pigments, biliverdin and bilirubin. These end products exert potent anti-inflammatory, antioxidant, anti-apoptotic, and anti-thrombotic actions. In addition, CO and bile pigments act to preserve vascular homeostasis at sites of arterial injury by influencing the proliferation, migration, and adhesion of vascular smooth muscle cells, endothelial cells, endothelial progenitor cells, or leukocytes. Several strategies are currently being developed to target HO-1 in vascular disease. Pharmacological induction of HO-1 by heme derivatives, dietary antioxidants, or currently available drugs, is a promising near-term approach, while HO-1 gene delivery is a long-term therapeutic goal. Direct administration of CO via inhalation or through the use of CO-releasing molecules and/or CO-sensitizing agents provides an attractive alternative approach in targeting HO-1. Furthermore, delivery of bile pigments, either alone or in combination with CO, presents another avenue for protecting against vascular disease. Since HO-1 and its products are potentially toxic, a major challenge will be to devise clinically effective therapeutic modalities that target HO-1 without causing any adverse effects.
journal_name
Curr Drug Targetsjournal_title
Current drug targetsauthors
Durante Wdoi
10.2174/1389450111009011504subject
Has Abstractpub_date
2010-12-01 00:00:00pages
1504-16issue
12eissn
1389-4501issn
1873-5592pii
BSP/CDT/E-Pub/00146journal_volume
11pub_type
杂志文章,评审abstract::Treatment of chronic myeloid leukemia (CML) with interferon-alpha (IFN-α) was introduced in the early 1980s. Several clinical trials showed a survival advantage for patients treated with IFN-α compared to conventional chemotherapy. Some patients achieved longstanding complete cytogenetic remissions (i.e. >2 log tumor ...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945011794815301
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journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945007783220605
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journal_title:Current drug targets
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journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945007782151324
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abstract::Molecularly targeting signaling pathways that are involved in the pathogenesis of hematopoietic malignancies may lead to more specific and efficacious therapies. Activation of the RAS signal transduction cascade is a common feature in the molecular pathogenesis of hematologic malignancies. A number of novel agents tar...
journal_title:Current drug targets
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journal_title:Current drug targets
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journal_title:Current drug targets
pub_type: 杂志文章,评审
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更新日期:2004-11-01 00:00:00
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journal_title:Current drug targets
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journal_title:Current drug targets
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journal_title:Current drug targets
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更新日期:2019-01-01 00:00:00
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journal_title:Current drug targets
pub_type: 杂志文章,评审
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更新日期:2010-05-01 00:00:00
abstract::Galectin-1 (Gal1) was the first identified member of the galectin family of beta-galactosidase-binding proteins. Gal1 has important roles in processes fundamental to growth and survival of an organism, including cell adhesion, cell proliferation and apoptosis, and is expressed in many tissues, including the nervous sy...
journal_title:Current drug targets
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abstract::Due to potential health benefits and the general assumption that natural products are safe, there is an increasing trend in the general population - including pregnant women - to supplement their diet with flavonoid-based food supplements. In addition, preclinical studies aim to prevent developmental adverse effects i...
journal_title:Current drug targets
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更新日期:2017-01-01 00:00:00
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journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450111007011281
更新日期:2010-10-01 00:00:00
abstract:BACKGROUND:Osteosarcoma is considered the most frequent primary bone malignancy. Lung metastasis is the leading cause of death and the most consistent factor for predicting negative patient outcome in osteosarcoma. Third-generation nitrogen-containing bisphosphonates, such as zoledronic acid, have been shown to reduce ...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1573399811666150615145409
更新日期:2018-01-01 00:00:00
abstract::Diacylglycerol (DAG) kinase (DGK) modulates the balance between the two signaling lipids, DAG and phosphatidic acid (PA), by phosphorylating (consuming) DAG to yield PA. Ten mammalian DGK isozymes have been identified to date. In addition to two or three cysteine-rich C1 domains (protein kinase C-like zinc finger stru...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945008785132394
更新日期:2008-08-01 00:00:00
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journal_title:Current drug targets
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journal_title:Current drug targets
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journal_title:Current drug targets
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journal_title:Current drug targets
pub_type: 杂志文章,评审
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journal_title:Current drug targets
pub_type: 杂志文章,评审
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更新日期:2016-01-01 00:00:00
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journal_title:Current drug targets
pub_type: 杂志文章
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更新日期:2015-08-25 00:00:00
abstract::Flavonoids are chromene analogues abundantly found in plants. It is always of curiosity to discover natural flavonoid structures, since living things, including human, are routinely exposed to these compounds through many dietaries. Indeed, numerous studies conducted so far on flavonoids to display their diverse biolo...
journal_title:Current drug targets
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更新日期:2021-01-20 00:00:00
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journal_title:Current drug targets
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更新日期:2016-01-01 00:00:00
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journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450117666160502151600
更新日期:2017-01-01 00:00:00
abstract::The development of novel T cell therapies to target leukemia has facilitated the translation of this approach for hematologic malignancies. Different methods of manufacturing leukemia-specific T cells have evolved, along with additional measures to increase the safety of this therapy. This is an overview of expanded T...
journal_title:Current drug targets
pub_type: 杂志文章,评审
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更新日期:2017-01-01 00:00:00
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journal_title:Current drug targets
pub_type: 杂志文章,评审
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更新日期:2005-03-01 00:00:00