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
Citations
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Beneficial effect of TLR4 blockade by a specific aptamer antagonist after acute myocardial infarction.
Marta Paz-García,Adrián Povo-Retana,Rafael I. Jaén,Patricia Prieto,Diego A. Peraza,Carlos Zaragoza,Macarena Hernández-Jiménez,D. Rodríguez Piñeiro,Javier Regadera,María Laura García-Bermejo,Esperanza Macarena Rodríguez-Serrano,Sergio Sánchez-García,María A. Moro,Ignacio Lizasoain,Carmen Delgado,Carmen Valenzuela,Lisardo Boscá +16 more
TL;DR: In this paper , an aptamer (4FT) that acts as a selective antagonist for human TLR4 has been investigated in isolated macrophages from different species and in a rat model of cardiac ischemia/reperfusion (I/R).
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Inactivation of Interleukin-4 Receptor α Signaling in Myeloid Cells Protects Mice From Angiotensin II/High Salt-Induced Cardiovascular Dysfunction Through Suppression of Fibrotic Remodeling.
Jianrui Song,Ryan A. Frieler,Thomas M. Vigil,Jun Ma,Frank Brombacher,Sascha N. Goonewardena,Daniel R. Goldstein,Richard M. Mortensen +7 more
TL;DR: In this paper, the role of myeloid-specific IL-4Rα signaling in cardiovascular remodeling induced by angiotensin II and high salt was investigated, and it was shown that reducing fibrosis was associated with significant preservation of myocardial function.
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Why animal model studies are lost in translation
TL;DR: The development of a flexible and dynamic conceptual paradigm that takes into account the totality of the evidence on the mechanisms of disease, and pathophysiologic stratification of patients to identify subpopulations with distinct pathogenetic mechanisms, are crucial for the development of new therapeutics.
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Assessing inflammation in Chinese subjects with subtypes of heart failure: an observational study of the Chinese PLA Hospital Heart Failure Registry.
TL;DR: Wang et al. as discussed by the authors compared the differences in inflammation biomarkers among Chinese patients with different subtypes of heart failure who have been identified to date, and the correlations between the inflammatory biomarkers and left ventricular ejection fraction of the heart failure subtypes were assessed.
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Relationship between residual viable myocardium and LV remodeling post-MI: Only part of the story
TL;DR: The perfusable tissue index (PTI) is another approach for detecting myocardial viability and reflects the fraction of the myocardium that is capable of rapidly exchanging water, or said another way that is perfusable by water, within a given volume of region of interest.
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