Regulation of the inflammatory response in cardiac repair

By Nikolaos G. Frangogiannis. Circulation Research, 2012

1,128 citations recorded by the source corpus.

Myocardial necrosis triggers an inflammatory reaction that clears the wound from dead cells and matrix debris, while activating reparative pathways necessary for scar formation. A growing body of evidence suggests that accentuation, prolongation or expansion of the post-infarction inflammatory response results in worse remodeling and dysfunction following myocardial infarction. This review manuscript discusses the cellular effectors and endogenous molecular signals implicated in suppression and containment of the inflammatory response in the infarcted heart. Clearance of apoptotic neutrophils, recruitment of inhibitory monocyte subsets and regulatory T cells, macrophage differentiation and pericyte/endothelial interactions may play an active role in restraining post-infarction inflammation. Multiple molecular signals may be involved in suppressing the inflammatory cascade. Negative regulation of toll-like receptor signaling, downmodulation of cytokine responses and termination of chemokine signals may be mediated through the concerted action of multiple suppressive pathways that prevent extension of injury and protect from adverse remodeling. Expression of soluble endogenous antagonists, decoy receptors, and post-translational processing of bioactive molecules may limit cytokine and chemokine actions. Interleukin (IL)-10, members of the Transforming Growth Factor (TGF)-β family, and pro-resolving lipid mediators (such as lipoxins, resolvins and protectins) may suppress pro-inflammatory signaling. In human patients with myocardial infarction, defective suppression and impaired resolution of inflammation may be important mechanisms in the pathogenesis of remodeling and in progression to heart failure. Understanding of inhibitory and pro-resolving signals in the infarcted heart and identification of patients with uncontrolled post-infarction inflammation and defective cardiac repair is needed to design novel therapeutic strategies.

Subfields: Cardiology and Cardiovascular Medicine, Immunology

View Paper: https://www.semanticscholar.org/paper/4edf4b7a1a62dc4baf68e821a86e1d8526ea4365

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cardiology and Cardiovascular Medicine

In Immunology

Citations in the corpus

Pathophysiology of Myocardial Infarction (2015, neutral): “of necrotic cells (the main source of proinflammatory stimuli), but is an active process that involves activation of multiple inhibitory pathways (39, 110).”
The Biological Basis for Cardiac Repair After Myocardial Infarction: From Inflammation to Fibrosis. (2016, background): “noninfarcted myocardium from the unwanted effects of unrestrained inflammation.(3,189) However, information on specific”
A Unifying Mechanism for Mitochondrial Superoxide Production during Ischemia-Reperfusion Injury. (2016, background): “Therefore, during the weeks and months following the initial IR injury there will be formation of fibrotic scar tissue to replace the dead cells along with extensive tissue remodeling (Frangogiannis, 2012).”
Neutrophils orchestrate post-myocardial infarction healing by polarizing macrophages towards a reparative phenotype (2016, background): “Subsequently, monocytederived macrophages are recruited to the heart to remove debris and apoptotic neutrophils, which leads to activation of reparative pathways necessary for scar formation.(1,3) Macrophages in the ischaemic myocardium exhibit high plasticity and are involved in both inflammatory a”
Mesenchymal stromal cell-derived exosomes attenuate myocardial ischaemia-reperfusion injury through miR-182-regulated macrophage polarization (2019, background): “inflammatory reaction are intimately associated with myocardial injury and scar formation.(2,3) In this process, macrophages play an important role in the modulation of cardiac inflammation.”
Systems Genetics Approach Identifies Gene Pathways and Adamts2 as Drivers of Isoproterenol-Induced Cardiac Hypertrophy and Cardiomyopathy in Mice (2016, background): “Heart failure (HF) is a common disorder characterized by impaired heart function, cardiac hypertrophy, and chamber remodeling (Frangogiannis, 2012).”