Deletion of Apoptosis Inhibitor of Macrophage (AIM)/CD5L Attenuates the Inflammatory Response and Infarct Size in Acute Myocardial Infarction

Nishikido, Toshiyuki; Oyama, Jun‐ichi; Shiraki, Aya; Komoda, Hiroshi; Node, Koichi

doi:10.1161/jaha.115.002863

Cited by 38 publications

(29 citation statements)

References 46 publications

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“…In our analyses, AGP1 predicted ASCVD, as well as all‐cause and CVD mortality in single‐ and multimarker models. CD5L inhibits macrophage apoptosis and is thought to regulate infarct size in animal models 37. SAA1 is an acute‐phase reactant that previously has been associated with future coronary disease in various populations 38.…”

Section: Discussionmentioning

confidence: 99%

Protein Biomarkers of Cardiovascular Disease and Mortality in the Community

Lyass

Courchesne

et al. 2018

JAHA

204

228

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BackgroundThe discovery of novel and highly predictive biomarkers of cardiovascular disease (CVD) has the potential to improve risk‐stratification methods and may be informative regarding biological pathways contributing to disease.Methods and ResultsWe used a discovery proteomic platform that targeted high‐value proteins for CVD to ascertain 85 circulating protein biomarkers in 3523 Framingham Heart Study participants (mean age, 62 years; 53% women). Using multivariable‐adjusted Cox models to account for clinical variables, we found 8 biomarkers associated with incident atherosclerotic CVD, 18 with incident heart failure, 38 with all‐cause mortality, and 35 with CVD death (false discovery rate, q<0.05 for all; P‐value ranges, 9.8×10−34 to 3.6×10−2). Notably, a number of regulators of metabolic and adipocyte homeostasis were associated with cardiovascular events, including insulin‐like growth factor 1 (IGF1), insulin‐like growth factor binding protein 1 (IGFBP1), insulin‐like growth factor binding protein 2 (IGFBP2), leptin, and adipsin. In a multimarker approach that accounted for clinical factors, growth differentiation factor 15 (GDF15) was associated with all outcomes. In addition, N‐terminal pro‐b‐type natriuretic peptide, C‐reactive protein, and leptin were associated with incident heart failure, and C‐type lectin domain family 3 member B (CLEC3B; tetranectin), N‐terminal pro‐b‐type natriuretic peptide, arabinogalactan protein 1 (AGP1), soluble receptor for advanced glycation end products (sRAGE), peripheral myelin protein 2 (PMP2), uncarboxylated matrix Gla protein (UCMGP), kallikrein B1 (KLKB1), IGFBP2, IGF1, leptin receptor, and cystatin‐C were associated with all‐cause mortality in a multimarker model.ConclusionsWe identified numerous protein biomarkers that predicted cardiovascular outcomes and all‐cause mortality, including biomarkers representing regulators of metabolic homeostasis and inflammatory pathways. Further studies are needed to validate our findings and define clinical utility, with the ultimate goal of improving strategies for CVD prevention.

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Section: Discussionmentioning

confidence: 99%

Protein Biomarkers of Cardiovascular Disease and Mortality in the Community

Lyass

Courchesne

et al. 2018

JAHA

204

228

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“…A series of studies have demonstrated that blockage of NF-κB could protect the heart against acute ischemic injury and inflammatory response [34]. NF-κB is localized in the cytoplasm in a complex with inhibitory proteins (IκBs) under normal conditions.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of the lncRNA Mirt1 Attenuates Acute Myocardial Infarction by Suppressing NF-κB Activation

Zhou

Huang

2017

Cell Physiol Biochem

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Background/Aims: The expression of a novel lncRNA, myocardial infarction associated transcript 1(Mirt1), has been shown to be upregulated in acute myocardial infarction (AMI). However, the role of Mirt1 in AMI is not clear. Methods: In this study, we analyzed the level of Mirt1 in cardiomyocytes and cardiac fibroblasts in AMI mice. Moreover, adenovirus mediated knockdown of Mirt1 was employed to clarify its roles in AMI mice or cultured cardiac fibroblasts. The cardiac functions and infarct size of AMI mice were examined, and tissues and cultured cells were collected and processed for histology and biochemical examination. Results: We demonstrated that Mirt1 was mainly expressed in cardiac fibroblasts, and that knockdown of Mirt1 improved cardiac functions, decreased cardiomyocytes apoptosis and attenuated inflammatory cell infiltration in vivo. Furthermore, knockdown of Mirt1 in cardiac fibroblasts not only attenuated the apoptosis of cardiomyocytes, but also suppressed the migration of macrophages under hypoxia in vitro. NF-κB signaling pathway, activated under hypoxia, was also inhibited by Mirt1 knockdown in fibroblasts. Conclusions: Knockdown of Mirt1 attenuates AMI injury presumably by decreasing cardiomyocytes apoptosis and reducing inflammatory cell infiltration. These effects could be attributed, at least partly, to inhibition of the NF-κB pathway, resulting in decreased expression of inflammatory factors.

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“…Studies have demonstrated that cardiomyocyte apoptosis takes place in heart samples from patients suffering from MI [2]. Inhibition of cardiomyocyte apoptosis MI-induced can lead to a decrease of the infarct size and an improvement of cardiac function [3][4][5]. Cardiac shock wave therapy (CSWT) is a novel approach that provides a new choice for severe CHD.…”

Section: Introductionmentioning

confidence: 99%

Cardiac Shock Wave Therapy Attenuates Cardiomyocyte Apoptosis after Acute Myocardial Infarction in Rats

Zhang

Shen

Liu

et al. 2018

Cell Physiol Biochem

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Background/Aims: Researches have showed that cardiac shock wave therapy (CSWT) could improve left ventricular function and attenuate LV remodeling of the ischemic heart. Apoptosis plays an important role in myocardial infarction and determines heart function and prognosis. However, it is still not clear whether CSWT is sufficient to attenuate acute myocardial infarction (AMI) induced cardiomyocyte apoptosis in vivo. In this study, we used a rat model to examine whether CSWT could attenuate cardiomyocyte apoptosis after AMI and to explore potential mechanisms. Methods: We generated an AMI rat model to investigate the function and possible regulatory mechanisms of CSWT. All rats were randomly divided into four groups: the sham-operated only group, sham-operated with SW treatment group, AMI only group, and AMI treated with SW treatment group.The rats were treated with a left anterior descending coronary artery ligation for 12h and then treated with or without CSWT (800 shots at 0.1 mJ/ mm²). Cytochrome c release was measured to analyze mitochondrial function and integrity. The apoptotic cell rate was determined by TUNEL assay. Western blot was used to analyze the cell apoptosis-, inflammation-, and survival-related signaling pathways. Results: First, the methodology of CSWT in the rat model of AMI was established. Second, CSWT attenuated the cardiomyocyte apoptosis rate in the infarct border zone. Third, CSWT suppressed the expression of apoptosis and inflammation molecules after AMI. Fourth, CSWT inhibited activation of the JNK pathway, which indicated inhibition of the cell inflammatory pathways and promotion of cardiomyocyte survival after AMI. Conclusion: These results indicate that CSWT exerts a protective effect against AMI-induced cardiomyocyte apoptosis, potentially by attenuating cytochrome c release from the mitochondria and inhibiting of the mitochondrial-dependent intrinsic apoptotic pathway. We also demonstrate that CSWT suppresses the JNK pathway and cardiomyocyte inflammation, which may also decrease cardiomyocyte apoptosis in vivo.

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Deletion of Apoptosis Inhibitor of Macrophage (AIM)/CD5L Attenuates the Inflammatory Response and Infarct Size in Acute Myocardial Infarction

Cited by 38 publications

References 46 publications

Protein Biomarkers of Cardiovascular Disease and Mortality in the Community

Protein Biomarkers of Cardiovascular Disease and Mortality in the Community

Inhibition of the lncRNA Mirt1 Attenuates Acute Myocardial Infarction by Suppressing NF-κB Activation

Cardiac Shock Wave Therapy Attenuates Cardiomyocyte Apoptosis after Acute Myocardial Infarction in Rats

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