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Inflammation in nonischemic heart disease: initiation by cardiomyocyte CaMKII and NLRP3 inflammasome signaling.
- Source :
-
American journal of physiology. Heart and circulatory physiology [Am J Physiol Heart Circ Physiol] 2019 Nov 01; Vol. 317 (5), pp. H877-H890. Date of Electronic Publication: 2019 Aug 23. - Publication Year :
- 2019
-
Abstract
- There is substantial evidence that chronic heart failure in humans and in animal models is associated with inflammation. Ischemic interventions such as myocardial infarction lead to necrotic cell death and release of damage associated molecular patterns, factors that signal cell damage and induce expression of proinflammatory chemokines and cytokines. It has recently become evident that nonischemic interventions are also associated with increases in inflammatory genes and immune cell accumulation in the heart and that these contribute to fibrosis and ventricular dysfunction. How proinflammatory responses are elicited in nonischemic heart disease which is not, at least initially, associated with cell death is a critical unanswered question. In this review we provide evidence supporting the hypothesis that cardiomyocytes are an initiating site of inflammatory gene expression in response to nonischemic stress. Furthermore we discuss the role of the multifunctional Ca <superscript>2+</superscript> /calmodulin-regulated kinase, CaMKIIδ, as a transducer of stress signals to nuclear factor-κB activation, expression of proinflammatory cytokines and chemokines, and priming and activation of the NOD-like pyrin domain-containing protein 3 (NLRP3) inflammasome in cardiomyocytes. We summarize recent evidence that subsequent macrophage recruitment, fibrosis and contractile dysfunction induced by angiotensin II infusion or transverse aortic constriction are ameliorated by blockade of CaMKII, of monocyte chemoattractant protein-1/C-C chemokine receptor type 2 signaling, or of NLRP3 inflammasome activation.
- Subjects :
- Animals
Disease Models, Animal
Fibrosis
Heart Diseases immunology
Heart Diseases pathology
Heart Diseases physiopathology
Humans
Inflammasomes immunology
Inflammation immunology
Inflammation pathology
Inflammation physiopathology
Inflammation Mediators immunology
Myocytes, Cardiac immunology
Myocytes, Cardiac pathology
NLR Family, Pyrin Domain-Containing 3 Protein immunology
Signal Transduction
Calcium-Calmodulin-Dependent Protein Kinase Type 2 metabolism
Heart Diseases enzymology
Inflammasomes metabolism
Inflammation enzymology
Inflammation Mediators metabolism
Myocytes, Cardiac enzymology
NLR Family, Pyrin Domain-Containing 3 Protein metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1539
- Volume :
- 317
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Heart and circulatory physiology
- Publication Type :
- Academic Journal
- Accession number :
- 31441689
- Full Text :
- https://doi.org/10.1152/ajpheart.00223.2019