Cell biological mechanisms in regulation of the post-infarction inflammatory response

Frangogiannis, Nikolaos G.

doi:10.1016/j.cophys.2017.09.001

Cited by 45 publications

(53 citation statements)

References 79 publications

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“…Monocyte and neutrophil migration is regulated by numerous CC and CXC chemokines 13,20 . We performed RNAseq and mined the data to detect CC and CXC chemokines.…”

Section: Cmcs Express CC and Cxc Chemokines Regulating Migration Of Nmentioning

confidence: 99%

Administration of cardiac mesenchymal cells modulates innate immunity in the acute phase of myocardial infarction in mice

Kang

Nasr

Guo

et al. 2020

Sci Rep

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Although cardiac mesenchymal cell (CMC) therapy mitigates post-infarct cardiac dysfunction, the underlying mechanisms remain unidentified. It is acknowledged that donor cells are neither appreciably retained nor meaningfully contribute to tissue regeneration—suggesting a paracrine-mediated mechanism of action. As the immune system is inextricably linked to wound healing/remodeling in the ischemically injured heart, the reparative actions of CMCs may be attributed to their immunoregulatory properties. The current study evaluated the consequences of CMC administration on post myocardial infarction (MI) immune responses in vivo and paracrine-mediated immune cell function in vitro. CMC administration preferentially elicited the recruitment of cell types associated with innate immunity (e.g., monocytes/macrophages and neutrophils). CMC paracrine signaling assays revealed enhancement in innate immune cell chemoattraction, survival, and phagocytosis, and diminished pro-inflammatory immune cell activation; data that identifies and catalogues fundamental immunomodulatory properties of CMCs, which have broad implications regarding the mechanism of action of CMCs in cardiac repair.

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“…Monocyte and neutrophil migration is regulated by numerous CC and CXC chemokines 13,20 . We performed RNAseq and mined the data to detect CC and CXC chemokines.…”

Section: Cmcs Express CC and Cxc Chemokines Regulating Migration Of Nmentioning

confidence: 99%

Administration of cardiac mesenchymal cells modulates innate immunity in the acute phase of myocardial infarction in mice

Kang

Nasr

Guo

et al. 2020

Sci Rep

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“…Beyond the pro-inflammatory and prohealing subtypes, there is a continuum of functional states, with some macrophages displaying characteristics of both classically defined phenotypes (Mosser and Edwards, 2008). In the infarcted myocardium, the controlled recruitment and activation of monocytes and macrophages is required for orchestrating tissue repair and neoangiogenesis to limit excessive scarring and fibrosis (Frangogiannis, 2018;Swirski and Nahrendorf, 2018). Unbalanced or impaired activation of the cells of the immune system after myocardial ischemia results in maladaptive ventricular dilatation, systolic or diastolic dysfunction and myocardial stiffness (Frangogiannis, 2014).…”

Section: Introductionmentioning

confidence: 99%

Engineering Immunomodulatory Biomaterials for Regenerating the Infarcted Myocardium

Bloise

Rountree

Polucha

et al. 2020

Front. Bioeng. Biotechnol.

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Coronary artery disease is a severe ischemic condition characterized by the reduction of blood flow in the arteries of the heart that results in the dysfunction and death of cardiac tissue. Despite research over several decades on how to reduce long-term complications and promote angiogenesis in the infarct, the medical field has yet to define effective treatments for inducing revascularization in the ischemic tissue. With this work, we have developed functional biomaterials for the controlled release of immunomodulatory cytokines to direct immune cell fate for controlling wound healing in the ischemic myocardium. The reparative effects of colony-stimulating factor (CSF-1), and anti-inflammatory interleukins 4/6/13 (IL4/6/13) have been evaluated in vitro and in a predictive in vivo model of ischemia (the skin flap model) to optimize a new immunomodulatory biomaterial that we use for treating infarcted rat hearts. Alginate hydrogels have been produced by internal gelation with calcium carbonate (CaCO 3) as carriers for the immunomodulatory cues, and their stability, degradation, rheological properties and release kinetics have been evaluated in vitro. CD14 positive human peripheral blood monocytes treated with the immunomodulatory biomaterials show polarization into pro-healing macrophage phenotypes. Unloaded and CSF-1/IL4 loaded alginate gel formulations have been implanted in skin flap ischemic wounds to test the safety and efficacy of the delivery system in vivo. Faster wound healing is observed with the new therapeutic treatment, compared to the wounds treated with the unloaded controls at day 14. The optimized therapy has been evaluated in a rat model of myocardial infarct (ischemia/reperfusion). Macrophage polarization toward healing phenotypes and global cardiac function measured with echocardiography and immunohistochemistry at 4 and 15 days demonstrate the therapeutic potential of the proposed immunomodulatory treatment in a clinically relevant infarct model.

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“…www.nature.com/scientificreports www.nature.com/scientificreports/ Here, we showed that CHF after MI is accompanied by myocardial inflammation, apoptosis and ventricular remodeling. After MI, inflammatory reactions are triggered by DAMPs, activating macrophages to coordinate inflammation and tissue repair; in addition, macrophages regulate autophagy to exert innate immune function 5,18 . Activating subsequent inflammatory/reparative pathways, the highly inflammatory factors trigger apoptosis in cardiomyocytes, cardiac hypertrophy and stiffness, differentiation of myofibroblasts, collagen accumulation, endothelial dysfunction, and endothelial-to-mesenchymal transition, and ensuing ventricular remodeling and impaired left ventricular function.…”

Section: Discussionmentioning

confidence: 99%

Qi Dan Li Xin pill improves chronic heart failure by regulating mTOR/p70S6k-mediated autophagy and inhibiting apoptosis

Shi

Huang

et al. 2020

Sci Rep

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Myocardial remodeling represents a key factor in chronic heart failure (CHF) development, and is characterized by chronic death of cardiomyocytes. Cardiac function changes may be attributed to inflammation, apoptosis and autophagy. This study assessed the effects of Qi Dan Li Xin Pill (QD) on heart function, inflammatory factors, autophagy and apoptosis in cardiac remodeling in CHF rats upon myocardial infarction (MI) induction.Male SD rats underwent a sham procedure or left anterior descending coronary artery (LADCA) ligation, causing MI. Twenty-eight days after modeling, the animals were treated daily with QD, valsartan and saline for 4 weeks. Echocardiography after 4 weeks of drug intervention revealed substantially improved left ventricular remodeling and cardiac function following QD treatment. As demonstrated by decreased IL-1β, IL-6 and TNF-α amounts, this treatment also inhibited the apoptotic process and protected the viability of the myocardium. These outcomes may be attributed to enhanced autophagy in cardiomyocytes, which further reduced pro-inflammatory and pro apoptotic effects. This process may be achieved by QD regulation of the mTOR/P70S6K signaling pathway, suggesting that the traditional Chinese medicine Qi Dan Li Xin pill is effective in heart protective treatment, and is worth further investigation.

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Cell biological mechanisms in regulation of the post-infarction inflammatory response

Cited by 45 publications

References 79 publications

Administration of cardiac mesenchymal cells modulates innate immunity in the acute phase of myocardial infarction in mice

Administration of cardiac mesenchymal cells modulates innate immunity in the acute phase of myocardial infarction in mice

Engineering Immunomodulatory Biomaterials for Regenerating the Infarcted Myocardium

Qi Dan Li Xin pill improves chronic heart failure by regulating mTOR/p70S6k-mediated autophagy and inhibiting apoptosis

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