Abstract:
BACKGROUND:A diet rich in saturated fat and sugars (Western diet, WD) induces myocardial expression of the NLRP3 inflammasome and dysfunction in mice. We therefore hypothesized that a diet enriched with an orally available NLRP3 inflammasome inhibitor could prevent WD-induced cardiac dysfunction in mice. METHODS:Ten-week-old CD-1 male mice were fed WD or standard diet (SD) for 8 weeks. The compound 16673-34-0, an orally active NLRP3 inhibitor, was added to the diet at a concentration of 100 mg/Kg. The plasmatic levels of the NLRP3 inflammasome inhibitor were measured. Food intake, body weight, and glucose tolerance were assessed. Cardiac systolic and diastolic functions were measured by Doppler echocardiography at baseline, 4 weeks, and 8 weeks. RESULTS:WD induced a significant increase in body weight (+14%, P = 0.02), impaired glucose tolerance (+34%, P = 0.03), and a significant increase in isovolumetric relaxation time (+129%, P = 0.03) and reduction in left ventricular ejection fraction (-10%, P = 0.03), as compared to standard chow diet (SD). The treatment with NLRP3 inhibitor in the diet prevented cardiac systolic and diastolic dysfunction (P < 0.05 for left ventricular ejection fraction, isovolumetric relaxation time, and myocardial performance index in WD with drug vs. WD without drug), without significant changes in heart rate and metabolic parameters. CONCLUSIONS:An orally available NLRP3 inhibitor prevented WD-induced cardiac dysfunction in obese mice.
journal_name
J Cardiovasc Pharmacoljournal_title
Journal of cardiovascular pharmacologyauthors
Carbone S,Mauro AG,Prestamburgo A,Halquist MS,Narayan P,Potere N,Mezzaroma E,Van Tassell BW,Abbate A,Toldo Sdoi
10.1097/FJC.0000000000000628subject
Has Abstractpub_date
2018-12-01 00:00:00pages
303-307issue
6eissn
0160-2446issn
1533-4023journal_volume
72pub_type
杂志文章abstract::To evaluate the safety and pharmacologic activity of ITF 296 in humans, three groups of healthy male normotensive subjects were studied. The first two groups (six subjects each) received, in ascending order, three dose levels of ITF 296 by 30-min intravenous infusion (group I, 0.1, 0.5, 1.0 microgram/kg/min; group II,...
journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,随机对照试验,评审
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abstract::MCI-154 is a potent nonglycoside and non-sympathomimetic cardiotonic agent with a pyridazinone structure. We assessed its cardiac and coronary vasodilator effects by use of isolated, blood-perfused papillary muscle, sinoatrial (SA) node, and atrioventricular (AV) node preparations of dogs. The drug (1-100 nmol) was in...
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journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
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更新日期:1995-08-01 00:00:00
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journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198500076-00018
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journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:
更新日期:1991-01-01 00:00:00
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journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198907000-00018
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journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:
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journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
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abstract::In conscious, spontaneously hypertensive rats (SHR) oral prazosin (0.03-3.0 mg/kg) resulted in dose-related reductions of systolic blood pressure measured with a tail cuff. In SHR whose tail artery blood pressure was continuously monitored the antihypertensive effect of prazosin (1.0 mg/kg, p.o.) was accompanied by a ...
journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
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更新日期:1993-01-01 00:00:00
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