The inflammatory response in myocardial injury, repair, and remodelling.
TLDR
Biomarker-based approaches are needed to identify patients with distinct pathophysiologic responses and to rationally implement inflammation-modulating strategies in patients with myocardial infarction.Abstract:
Myocardial infarction triggers an intense inflammatory response that is essential for cardiac repair, but which is also implicated in the pathogenesis of postinfarction remodelling and heart failure. Signals in the infarcted myocardium activate toll-like receptor signalling, while complement activation and generation of reactive oxygen species induce cytokine and chemokine upregulation. Leukocytes recruited to the infarcted area, remove dead cells and matrix debris by phagocytosis, while preparing the area for scar formation. Timely repression of the inflammatory response is critical for effective healing, and is followed by activation of myofibroblasts that secrete matrix proteins in the infarcted area. Members of the transforming growth factor β family are critically involved in suppression of inflammation and activation of a profibrotic programme. Translation of these concepts to the clinic requires an understanding of the pathophysiological complexity and heterogeneity of postinfarction remodelling in patients with myocardial infarction. Individuals with an overactive and prolonged postinfarction inflammatory response might exhibit left ventricular dilatation and systolic dysfunction and might benefit from targeted anti-IL-1 or anti-chemokine therapies, whereas patients with an exaggerated fibrogenic reaction can develop heart failure with preserved ejection fraction and might require inhibition of the Smad3 (mothers against decapentaplegic homolog 3) cascade. Biomarker-based approaches are needed to identify patients with distinct pathophysiologic responses and to rationally implement inflammation-modulating strategies.read more
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References
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Neutrophil chemoattractants generated in two phases during reperfusion of ischemic myocardium in the rabbit. Evidence for a role for C5a and interleukin-8.
TL;DR: Observations suggest a sequential release of chemoattractants: the first, C5a is generated in interstitial fluid, followed by IL-8 generated by infiltrating neutrophils, which would be expected to be indirectly dependent on C4a production over the time period studied.
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IL-1 Induces Proinflammatory Leukocyte Infiltration and Regulates Fibroblast Phenotype in the Infarcted Myocardium
TL;DR: IL-1 may orchestrate fibroblasts responses in the infarct; early stimulation of fibroblast IL-1R1 signaling during the inflammatory phase may prevent premature activation of a matrix-synthetic contractile phenotype until the wound is cleared, and theinfarct microenvironment can support mesenchymal cell growth.
Journal ArticleDOI
Induction of Monocyte Chemoattractant Protein-1 in the Small Veins of the Ischemic and Reperfused Canine Myocardium
Ajith Kumar,Christie M. Ballantyne,Lloyd H. Michael,Gilbert L. Kukielka,Keith A. Youker,Merry L. Lindsey,Hal K. Hawkins,Holly H. Birdsall,Charles R. Mackay,Gregory J. LaRosa,Roger D. Rossen,C. Wayne Smith,Mark L. Entman +12 more
TL;DR: A significant role is suggested for MCP-1 in monocyte trafficking in the reperfused myocardium as well as in the endothelium of a specific class of small veins immediately after reperfusion.
Journal ArticleDOI
Aging-related defects are associated with adverse cardiac remodeling in a mouse model of reperfused myocardial infarction.
Marcin Bujak,Hyuk Jung Kweon,Khaled Chatila,Na Li,George E. Taffet,Nikolaos G. Frangogiannis +5 more
TL;DR: Although young mice exhibit a robust post-infarction inflammatory response and form dense collagenous scars, senescent mice show suppressed inflammation, delayed granulation tissue formation, and markedly reduced collagen deposition, which might contribute to adverse remodeling.
Journal ArticleDOI
Bone marrow-derived cells contribute to infarct remodelling
Helge Möllmann,Holger Nef,Sawa Kostin,Christof von Kalle,Ingo H. Pilz,Michael Weber,Jutta Schaper,Christian W. Hamm,Albrecht Elsässer +8 more
TL;DR: BMC-derived fibroblast and myofibroblasts as well as neoangiogenesis significantly contribute to post-infarction scar formation and might be important in scar tissue remodelling.
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