Abstract
ABSTRACT:: Extensive necrosis of ischemic cardiomyocytes in the infarcted myocardium activates the innate immune response triggering an intense inflammatory reaction. Release of danger signals from dying cells and damaged matrix activates the complement cascade and stimulates Toll-like receptor/interleukin-1 signaling, resulting in the activation of the nuclear factor-κB system and induction of chemokines, cytokines, and adhesion molecules. Subsequent infiltration of the infarct with neutrophils and mononuclear cells serves to clear the wound from dead cells and matrix debris, while stimulating reparative pathways. In addition to its role in repair of the infarcted heart and formation of a scar, the immune system is also involved in adverse remodeling of the infarcted ventricle. Overactive immune responses and defects in suppression, containment, and resolution of the postinfarction inflammatory reaction accentuate dilative remodeling in experimental models and may be associated with chamber dilation, systolic dysfunction, and heart failure in patients surviving a myocardial infarction. Interventions targeting the inflammatory response to attenuate adverse remodeling may hold promise in patients with myocardial infarction that exhibit accentuated, prolonged, or dysregulated immune responses to the acute injury.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 185-195 |
| Number of pages | 11 |
| Journal | Journal of Cardiovascular Pharmacology |
| Volume | 63 |
| Issue number | 3 |
| DOIs | |
| State | Published - 2014 |
Fingerprint
Keywords
- Cardiac remodeling
- Chemokines
- Cytokines
- Innate immunity
- Leukocytes
- Myocardial infarction
- Toll-like receptors
ASJC Scopus subject areas
- Pharmacology
- Cardiology and Cardiovascular Medicine
Cite this
The immune system and the remodeling infarcted heart : Cell biological insights and therapeutic opportunities. / Frangogiannis, Nikolaos G.
In: Journal of Cardiovascular Pharmacology, Vol. 63, No. 3, 2014, p. 185-195.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The immune system and the remodeling infarcted heart
T2 - Cell biological insights and therapeutic opportunities
AU - Frangogiannis, Nikolaos G.
PY - 2014
Y1 - 2014
N2 - ABSTRACT:: Extensive necrosis of ischemic cardiomyocytes in the infarcted myocardium activates the innate immune response triggering an intense inflammatory reaction. Release of danger signals from dying cells and damaged matrix activates the complement cascade and stimulates Toll-like receptor/interleukin-1 signaling, resulting in the activation of the nuclear factor-κB system and induction of chemokines, cytokines, and adhesion molecules. Subsequent infiltration of the infarct with neutrophils and mononuclear cells serves to clear the wound from dead cells and matrix debris, while stimulating reparative pathways. In addition to its role in repair of the infarcted heart and formation of a scar, the immune system is also involved in adverse remodeling of the infarcted ventricle. Overactive immune responses and defects in suppression, containment, and resolution of the postinfarction inflammatory reaction accentuate dilative remodeling in experimental models and may be associated with chamber dilation, systolic dysfunction, and heart failure in patients surviving a myocardial infarction. Interventions targeting the inflammatory response to attenuate adverse remodeling may hold promise in patients with myocardial infarction that exhibit accentuated, prolonged, or dysregulated immune responses to the acute injury.
AB - ABSTRACT:: Extensive necrosis of ischemic cardiomyocytes in the infarcted myocardium activates the innate immune response triggering an intense inflammatory reaction. Release of danger signals from dying cells and damaged matrix activates the complement cascade and stimulates Toll-like receptor/interleukin-1 signaling, resulting in the activation of the nuclear factor-κB system and induction of chemokines, cytokines, and adhesion molecules. Subsequent infiltration of the infarct with neutrophils and mononuclear cells serves to clear the wound from dead cells and matrix debris, while stimulating reparative pathways. In addition to its role in repair of the infarcted heart and formation of a scar, the immune system is also involved in adverse remodeling of the infarcted ventricle. Overactive immune responses and defects in suppression, containment, and resolution of the postinfarction inflammatory reaction accentuate dilative remodeling in experimental models and may be associated with chamber dilation, systolic dysfunction, and heart failure in patients surviving a myocardial infarction. Interventions targeting the inflammatory response to attenuate adverse remodeling may hold promise in patients with myocardial infarction that exhibit accentuated, prolonged, or dysregulated immune responses to the acute injury.
KW - Cardiac remodeling
KW - Chemokines
KW - Cytokines
KW - Innate immunity
KW - Leukocytes
KW - Myocardial infarction
KW - Toll-like receptors
UR - http://www.scopus.com/inward/record.url?scp=84896318665&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84896318665&partnerID=8YFLogxK
U2 - 10.1097/FJC.0000000000000003
DO - 10.1097/FJC.0000000000000003
M3 - Article
C2 - 24072174
AN - SCOPUS:84896318665
VL - 63
SP - 185
EP - 195
JO - Journal of Cardiovascular Pharmacology
JF - Journal of Cardiovascular Pharmacology
SN - 0160-2446
IS - 3
ER -