Abstract:
OBJECTIVE:3-Methylcholanthrene (MC), a polycylic aromatic hydrocarbon, induces atherogenesis in mice fed an atherogenic diet. In this study, we tested the hypothesis that MC would induce DNA adducts in mouse aortic smooth muscle cells (SMCs) and that cytochrome P4501B1 (CYP1B1) plays an important role in the activation of MC to genotoxic intermediates. METHODS:Cultured SMCs were treated with MC or the vehicle dimethyl sulfoxide (DMSO), and DNA was isolated after 24 h. In some experiments, the cells were pre-treated with the CYP1B1 inhibitor 1-ethynylpyrene (EP) prior to exposure to MC. DNA adducts were determined by the 32P-postlabeling assay. Aryl hydrocarbon hydroxylase assay was measured by fluorimetry. RESULTS:MC induced formation of 12 DNA adducts that were not observed in DMSO-treated cells. DNA adduct formation was dose-dependent, with maximum response observed at 3 microM. Pre-treatment of cells with EP dramatically suppressed DNA adduct formation by MC. MC treatment caused induction of CYP1B1, but not CYP1A1. CONCLUSION:The induction of high levels of multiple DNA adducts in SMCs by MC suggests that SMCs have a functional enzymatic machinery capable of metabolically activating MC to genotoxic metabolites. The significant inhibition by EP of MC-induced DNA adduct formation indicated that CYP1B1 was the primary CYP enzyme responsible for formation of genotoxic metabolites that may play a role in the induction of atherosclerosis by MC.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Moorthy B,Miller KP,Jiang W,Ramos KSdoi
10.1016/s0008-6363(01)00536-3subject
Has Abstractpub_date
2002-03-01 00:00:00pages
1002-9issue
4eissn
0008-6363issn
1755-3245pii
S0008636301005363journal_volume
53pub_type
杂志文章abstract:OBJECTIVE:The function of angiotensin converting enzyme (ACE) at cell sites of high collagen turnover, such as heart valves, is uncertain. The aim of this study was to assess ACE and kininase-II-like activities and collagen turnover in cultured valvular interstitial cells of the adult rat heart. METHODS:The valvular i...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1995-01-01 00:00:00
abstract::Tension and action potentials have been measured simultaneously from isolated cat papillary muscles. Two groups of experiments are described. In the first group, the external conditions under which the muscle contracted were changed. Specifically, stimulation rate, extra-cellular [Ca++], extracellular [Na++] were alte...
journal_title:Cardiovascular research
pub_type: 杂志文章
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvp285
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abstract:AIMS:Current mechanisms driving cardiac pacemaker function have focused on ion channel and gap junction channel function, which are essential for action potential generation and propagation between pacemaker cells. However, pacemaker cells also harbour desmosomes that structurally anchor pacemaker cells to each other i...
journal_title:Cardiovascular research
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doi:10.1093/cvr/cvw083
更新日期:2016-08-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvs369
更新日期:2013-03-01 00:00:00
abstract:OBJECTIVE:The aim was to investigate the ventricular/vascular coupling of the intact right heart under conditions of normal operation and acute pulmonary hypertension. METHODS:Right ventricular contractility was obtained by calculating the end systolic pressure-volume relationship (Ees) and the effective pulmonary art...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/26.9.839
更新日期:1992-09-01 00:00:00
abstract::When the vagus nerves are stimulated with one burst of pulses per minute, but each burst is placed at a different time in the cardiac cycle, a "vagal effect curve" can be derived which displays the changes in cardiac cycle length (CCL) as a function of the elapsed time from the stimulus. This curve consists of a prima...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/18.2.75
更新日期:1984-02-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(01)00469-2
更新日期:2002-02-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(01)00408-4
更新日期:2001-12-01 00:00:00
abstract::Cardiomyocytes are long-lived post-mitotic cells with limited regenerative capacity. Proper cardiomyocyte function depends critically on the maintenance of a healthy homeostasis of protein expression, folding, assembly, trafficking, function, and degradation, together commonly referred to as proteostasis. Impairment o...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvv265
更新日期:2016-04-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/25.7.603
更新日期:1991-07-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2004.03.018
更新日期:2004-08-01 00:00:00
abstract:AIMS:Antihypertensive drugs are included in the medical therapy of vascular Ehlers-Danlos syndrome (vEDS). The β-blocker celiprolol has been suggested to prevent arterial damage in vEDS, but the underlying mechanism remains unclear. It is also unknown whether the widely used angiotensin II receptor type 1 antagonist lo...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvz095
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journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/s0008-6363(03)00337-7
更新日期:2003-07-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/26.1.3
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pub_type: 杂志文章
doi:10.1093/cvr/28.3.312
更新日期:1994-03-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvt074
更新日期:2013-09-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/14.4.223
更新日期:1980-04-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 临床试验,杂志文章
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更新日期:2013-08-01 00:00:00
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doi:10.1093/cvr/28.9.1385
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更新日期:2011-02-15 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvv251
更新日期:2016-02-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvt080
更新日期:2013-07-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvu068
更新日期:2014-06-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(00)00140-1
更新日期:2000-09-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvp065
更新日期:2009-07-15 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章,评审
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更新日期:2002-03-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/18.8.514
更新日期:1984-08-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvt021
更新日期:2013-05-01 00:00:00