Abstract
Background:
We identified an interleukin-1 receptor family member, ST2, as a gene markedly induced by mechanical strain in cardiac myocytes and hypothesized that ST2 participates in the acute myocardial response to stress and injury.
Methods and results:
ST2 mRNA was induced in cardiac myocytes by mechanical strain (4.7+/-0.9-fold) and interleukin-1beta (2.0+/-0.2-fold). Promoter analysis revealed that the proximal and not the distal promoter of ST2 is responsible for transcriptional activation in cardiac myocytes by strain and interleukin-1beta. In mice subjected to coronary artery ligation, serum ST2 was transiently increased compared with unoperated controls (20.8+/-4.4 versus 0.8+/-0.8 ng/mL, P<0.05). Soluble ST2 levels were increased in the serum of human patients (N=69) 1 day after myocardial infarction and correlated positively with creatine kinase (r=0.41, P<0.001) and negatively with ejection fraction (P=0.02).
Conclusions:
These data identify ST2 release in response to myocardial infarction and suggest a role for this innate immune receptor in myocardial injury.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Angiotensin II / pharmacology
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Angiotensin Receptor Antagonists
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Animals
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Animals, Newborn
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Biomarkers / blood
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Cells, Cultured
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Disease Models, Animal
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / physiology
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Humans
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Imidazoles / pharmacology
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Interleukin-1 / pharmacology
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Interleukin-1 Receptor-Like 1 Protein
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Interleukin-4 / pharmacology
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Lipopolysaccharides / pharmacology
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Membrane Proteins / blood
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Mice
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Mice, Inbred C57BL
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Myocardial Infarction / blood
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Myocardial Infarction / metabolism*
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Myocardium / cytology
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Myocardium / metabolism*
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Nuclease Protection Assays
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Phorbol Esters / pharmacology
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Promoter Regions, Genetic / drug effects
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Promoter Regions, Genetic / physiology
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Pyridines / pharmacology
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RNA, Messenger / metabolism
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Rats
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Rats, Sprague-Dawley
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Receptor, Angiotensin, Type 1
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Receptors, Cell Surface
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Receptors, Interleukin
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Receptors, Interleukin-1 / blood
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Receptors, Interleukin-1 / genetics
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Receptors, Interleukin-1 / metabolism*
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Stress, Mechanical
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Stroke Volume
Substances
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Angiotensin Receptor Antagonists
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Biomarkers
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CP 191166
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IL1RL1 protein, human
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Il1rl1 protein, mouse
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Imidazoles
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Interleukin-1
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Interleukin-1 Receptor-Like 1 Protein
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Lipopolysaccharides
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Membrane Proteins
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Phorbol Esters
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Pyridines
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RNA, Messenger
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Receptor, Angiotensin, Type 1
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Receptors, Cell Surface
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Receptors, Interleukin
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Receptors, Interleukin-1
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ST2 protein, rat
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Angiotensin II
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Interleukin-4