Abstract
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 postinfarction 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 postinfarction 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 posttranslational processing of bioactive molecules may limit cytokine and chemokine actions. Interleukin-10, members of the transforming growth factor-β family, and proresolving lipid mediators (such as lipoxins, resolvins, and protectins) may suppress proinflammatory 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 proresolving signals in the infarcted heart and identification of patients with uncontrolled postinfarction inflammation and defective cardiac repair is needed to design novel therapeutic strategies.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 159-173 |
| Number of pages | 15 |
| Journal | Circulation Research |
| Volume | 110 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 6 2012 |
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Keywords
- chemokine
- cytokine
- mononuclear cells
- myocardial infarction
- resolution of inflammation
ASJC Scopus subject areas
- Physiology
- Cardiology and Cardiovascular Medicine
Cite this
Regulation of the inflammatory response in cardiac repair. / Frangogiannis, Nikolaos G.
In: Circulation Research, Vol. 110, No. 1, 06.01.2012, p. 159-173.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Regulation of the inflammatory response in cardiac repair
AU - Frangogiannis, Nikolaos G.
PY - 2012/1/6
Y1 - 2012/1/6
N2 - 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 postinfarction 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 postinfarction 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 posttranslational processing of bioactive molecules may limit cytokine and chemokine actions. Interleukin-10, members of the transforming growth factor-β family, and proresolving lipid mediators (such as lipoxins, resolvins, and protectins) may suppress proinflammatory 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 proresolving signals in the infarcted heart and identification of patients with uncontrolled postinfarction inflammation and defective cardiac repair is needed to design novel therapeutic strategies.
AB - 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 postinfarction 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 postinfarction 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 posttranslational processing of bioactive molecules may limit cytokine and chemokine actions. Interleukin-10, members of the transforming growth factor-β family, and proresolving lipid mediators (such as lipoxins, resolvins, and protectins) may suppress proinflammatory 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 proresolving signals in the infarcted heart and identification of patients with uncontrolled postinfarction inflammation and defective cardiac repair is needed to design novel therapeutic strategies.
KW - chemokine
KW - cytokine
KW - mononuclear cells
KW - myocardial infarction
KW - resolution of inflammation
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UR - http://www.scopus.com/inward/citedby.url?scp=84855371090&partnerID=8YFLogxK
U2 - 10.1161/CIRCRESAHA.111.243162
DO - 10.1161/CIRCRESAHA.111.243162
M3 - Article
C2 - 22223212
AN - SCOPUS:84855371090
VL - 110
SP - 159
EP - 173
JO - Circulation Research
JF - Circulation Research
SN - 0009-7330
IS - 1
ER -