Interleukin-1β blockade improves cardiac remodelling after myocardial infarction without interrupting the inflammasome in the mouse.
Interleukin-1β blockade improves cardiac remodelling after myocardial infarction without interrupting the inflammasome in the mouse.
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DOI：
10.1113/expphysiol.2012.069831
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发表时间：
2013-03
影响因子：
2.7
通讯作者：
Abbate A
中科院分区：
文献类型：
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作者：
Toldo S;Mezzaroma E;Van Tassell BW;Farkas D;Marchetti C;Voelkel NF;Abbate A
The formation of the cryopyrin inflammasome in the heart induces an intense inflammatory response during acute myocardial infarction (AMI), which mediates further damage and promotes adverse cardiac remodeling. Active interleukin-1β (IL-1β) is a key product of the inflammasome, being cleaved by active caspase-1. The aim of this study was to dissect the role of IL-1β from that of the inflammasome by using a neutralizing monoclonal antibody directed against IL-1β and measuring the intensity of the inflammatory response, the activity of caspase-1 in the inflammasome, cardiomyocyte apoptosis, and cardiac remodeling in a mouse model of non-reperfused AMI. A mouse monoclonal IgG2a antibody directed against IL-1β (10 mg/Kg [IL-1β-AB]) was given i.p. immediately after surgery and then repeated 1 week later. Cardiac tissue was analyzed at 72 hours after surgery in a subgroup of mice for inflammasome aggregates and caspase-1 activity (inflammasome) and for DNA fragmentation and caspase-3 activity (apoptosis). All sham-operated mice were alive at 10 weeks, whereas 40% of the control-AB-treated mice and 30% of the IL-1β-AB-treated mice died during the 4 weeks after surgery. When compared with vehicle, treatment with the IL-1β-AB did not affect inflammasome formation or caspase-1 activation in the heart tissue at 72 hours after AMI nor circulating plasma IL-6 levels, but did inhibit cardiomyocyte apoptosis, limit left ventricular enlargement by 40% (P<0.01) and improve systolic dysfunction by 17% (P<0.01) after AMI. These findings suggest that IL-1β mediates the deleterious effects on the heart during sterile inflammatory response.
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影响因子：
20.1
作者：
Frangogiannis NG
通讯作者：
Frangogiannis NG
影响因子：
3.8
作者：
Osborn, O.;Brownell, S. E.;Sanchez-Alavez, M.;Salomon, D.;Gram, H.;Bartfai, T.
通讯作者：
Bartfai, T.
影响因子：
6.8
作者：
Abbate, Antonio;Van Tassell, Benjamin W.;Biondi-Zoccai, Giuseppe G. L.
通讯作者：
Biondi-Zoccai, Giuseppe G. L.
DOI：
10.1067/s0894-7317(03)00399-7
发表时间：
2003-08-01
影响因子：
6.5
作者：
Broberg, CS;Pantely, GA;Hohimer, AR
通讯作者：
Hohimer, AR
影响因子：
30.5
作者：
通讯作者：
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