Anakinra in Experimental Acute Myocardial Infarction—Does Dosage or Duration of Treatment Matter?

Salloum, Fadi N.; Chau, Vinh Q.; Varma, Amit; Hoke, Nicholas N; Toldo, Stefano; Biondi‐Zoccai, Giuseppe; Crea, Filippo; Vetrovec, George W.; Abbate, Antonio

doi:10.1007/s10557-008-6154-3

Cited by 32 publications

(20 citation statements)

References 28 publications

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“…In this model, we found that time of treatment was sufficient to reduce adverse remodeling in the long term without rebound effects due to interruption of the treatment (37,38). However, considering that anakinra preserved the contractile reserve at 3 d but not at 4 months, we speculate that a longer treatment with anakinra may be needed.…”

Section: Discussionmentioning

confidence: 76%

Role of Interleukin-1 in Radiation-Induced Cardiomyopathy

Mezzaroma

Mikkelsen

Toldo

et al. 2015

Mol Med

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Section: Discussionmentioning

confidence: 76%

Role of Interleukin-1 in Radiation-Induced Cardiomyopathy

Mezzaroma

Mikkelsen

Toldo

et al. 2015

Mol Med

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“…A role of apoptosis, an immunologically silent cell-death form, in myocardial IRI has been repeatedly proposed, but these studies have typically used terminal deoxynucleotidyltransferasemediated dUTP nick end labeling assay, which is not specific for apoptosis and additionally detects pyroptosis and other cell-death forms. 4,5,17,19 Our in vivo kinetic studies demonstrate that inflammasome activation precedes apoptosis (Figure 2). Additionally, Nlrp3 deficiency is protective in myocardial IRI.…”

Section: 5152mentioning

confidence: 75%

“…Several groups have shown that inflammasome inhibition improves cardiac remodeling and function at later time points. 4,5,67 Because aPC ameliorates angiotensin II-triggered myocardial remodeling, 22 an improved outcome after aPC-mediated inflammasome restriction seems conceivable, but this remains to be shown.…”

Section: 5152mentioning

confidence: 99%

“…[1][2][3] Induction of interleukin-1b (IL-1b) and IL-18, which are controlled by the Nlrp3 inflammasome, contribute to the tissue-disruptive and proinflammatory responses. 4,5 Importantly, Nlrp3 inflammasome inhibition reduces infarct size, attenuates adverse cardiac remodeling, and preserves cardiac function in animal models of MI. [6][7][8] The inflammasome is a signaling platform detecting pathogenic microorganisms and sterile stressors.…”

Section: Introductionmentioning

confidence: 99%

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Cytoprotective activated protein C averts Nlrp3 inflammasome–induced ischemia-reperfusion injury via mTORC1 inhibition

Nazir

Gadi

Al‐Dabet

et al. 2017

Blood

139

129

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“…24) IL-1Ra has been shown to have a cardioprotective function. [25][26][27][28] Although the cardioprotective effects of hexarelin have been partially revealed by many studies, the action of hexarelin on myocardial I/R injury in vivo have not been fully confirmed, whereas the underlying mechanisms remain unknown. In our study, using rat models of myocardial I/R, we attempted to observe the effects of hexarelin treatment on myocardial I/R injury, as well as clarify the role of the IL-1 signaling pathway in the cardiovascular action of hexarelin.…”

mentioning

confidence: 99%

The Growth Hormone Secretagogue Hexarelin Protects Rat Cardiomyocytes From <i>in vivo</i> Ischemia/Reperfusion Injury Through Interleukin-1 Signaling Pathway

Huang

Zhang

et al. 2017

Int. Heart J.

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SummaryHexarelin, a synthetic growth hormone-releasing peptide, has been proven to possess cardioprotective actions through its binding to the growth hormone secretagogue receptor (GHSR) 1a and the non-GHSR receptor CD36. However, its effect on myocardial ischemia/reperfusion (I/R) injury has not been fully clarified in vivo. We aimed to determine whether hexarelin treatment could protect cardiomyocytes from I/R injury and to examine the underlying mechanisms. In vivo hearts of male SD rats underwent 30 minutes of ischemia by left coronary artery ligation followed by reperfusion. The rats were then treated subcutaneously twice daily with hexarelin [100 μg/kg·day], ghrelin [400 μg/ kg·day], or saline for 7 days. Echocardiography, malondialdehyde detection, and histochemical staining were performed after treatment. In addition, Western blot was used to examine the expression levels of IL-1β, IL-1Ra, and IL-1RI. Our study showed that hexarelin treatment improved cardiac systolic function, decreased malondialdehyde production, and increased the number of surviving cardiomyocytes. The beneficial effects of hexarelin treatment were slightly superior to those of equimolar ghrelin treatment. We meanwhile confirmed that hexarelin induced down-regulation of IL-1β expression and up-regulation of IL-1Ra expression in I/R myocardium, which could be neutralized by the GHSR antagonist A cute myocardial infarction, which is caused by a sudden embolism of the coronary arteries, is a leading cause of mortality. As the primary clinical therapy for treatment of myocardial infarction, myocardial reperfusion can also aggravate cardiac injury. 1) Its mechanism includes calcium overload, cardiomyocyte apoptosis, and reactive oxygen species (ROS) accumulation.2-5) Finding a strategy to alleviate myocardial I/R injury has become a hot research field in cardiology.In vivo I/R models can cause regional myocardial I/R injury by ligating the left anterior descending coronary artery, which have been widely used to mimic the process of myocardial infarction and subsequent reperfusion.6) Compared to the in vitro global I/R models, in vivo I/R models can not only reveal changes in hemodynamics, and cardiac structure and function after I/R, but also display the impact of molecules in reperfusion flow on I/R myocardium, such as ROS and inflammation cytokines.7) The in vivo I/R models are more consistent with the pathophysiological process of myocardial I/R injury.Ghrelin, a growth hormone-releasing peptide produced in the stomach, is an endogenous ligand of growth hormone secretagogue receptor (GHSR) 1a. Previous studies have demonstrated the cardioprotective effects of exogenous ghrelin administration. 8) Hexarelin, a synthetic analog of ghrelin, shows effects similar to those of ghrelin and is more chemically stable, making it a potential alternative to ghrelin. Its beneficial action on the cardiovascular system has been reported by a lot of research, including inhibition of cardiomyocyte apoptosis, [9][10][11] anti-atherosclerosis, 12,13) impro...

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Anakinra in Experimental Acute Myocardial Infarction—Does Dosage or Duration of Treatment Matter?

Abstract: Anakinra inhibits apoptosis and ameliorates cardiac remodeling up to 4 weeks after infarction. A 2-week regimen is superior to a 1-week regimen, whereas a higher dose did not provide any further benefit over standard doses.

Cited by 32 publications

References 28 publications

Role of Interleukin-1 in Radiation-Induced Cardiomyopathy

Role of Interleukin-1 in Radiation-Induced Cardiomyopathy

Cytoprotective activated protein C averts Nlrp3 inflammasome–induced ischemia-reperfusion injury via mTORC1 inhibition

The Growth Hormone Secretagogue Hexarelin Protects Rat Cardiomyocytes From <i>in vivo</i> Ischemia/Reperfusion Injury Through Interleukin-1 Signaling Pathway

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