Clec4e-Receptor Signaling in Myocardial Repair After Ischemia-Reperfusion Injury

Autor: Denise Veltman, Piet Claus, Ellen Caluwé, Maarten Vanhaverbeke, Uwe Himmelreich, Stefan Janssens, Peter Pokreisz, Peter Sinnaeve, Willy Gsell, Ming Wu, Hilde Gillijns
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Pathology
PRR
pattern recognition receptor
TnT
troponin T
Angiogenesis
CAD
coronary artery disease
NS
not significant
DAMP
damage-associated molecular pattern
SMC
smooth muscle cell
MPO
myeloperoxidase
myocardial remodeling
Car3
carbonic anhydrase 3
Transcriptome
Myocyte
magnetic resonance imaging
CMC
cardiac myocyte
Cxcr2
CXC chemokine receptor 2
ANOVA
analysis of variance
STEMI
ST-segment elevation myocardial infarction
I/R
ischemia-reperfusion
ECM
extracellular matrix
LAD
left anterior descending coronary artery
medicine.symptom
Grk2
G protein–coupled receptor kinase 2
Cardiology and Cardiovascular Medicine
Extracellular matrix organization
medicine.medical_specialty
qRT-PCR
quantitative reverse transcription polymerase chain reaction
ischemia-reperfusion injury
Ischemia
Inflammation
Downregulation and upregulation
Cxcl2
CXC chemokine ligand 2
medicine
CLEC4E
LV
left ventricular
CLEC4E
C-type lectin domain family 4 member E
business.industry
medicine.disease
Efna2
ephrin A2
WT
wild-type
ESV
end-systolic volume
AMI
acute myocardial infarction
inflammation
RNA
ribonucleic acid
ACS
acute coronary syndrome
Preclinical Research
hs-TnI
high-sensitivity troponin I
business
Reperfusion injury
MRI
magnetic resonance imaging
Zdroj: JACC: Basic to Translational Science
Popis: Visual Abstract
Highlights • The role of the CLEC4E during myocardial healing after ischemia-reperfusion injury is unknown. • CLEC4E deletion is associated with reduced cardiac injury, inflammation, and left ventricular structural and functional remodeling. • CLEC4E is a promising target to modulate myocardial inflammation and enhance repair after ischemia-reperfusion injury.
Summary The bacterial C-type lectin domain family 4 member E (CLEC4E) has an important role in sterile inflammation, but its role in myocardial repair is unknown. Using complementary approaches in porcine, murine, and human samples, we show that CLEC4E expression levels in the myocardium and in blood correlate with the extent of myocardial injury and left ventricular (LV) functional impairment. CLEC4E expression is markedly increased in the vasculature, cardiac myocytes, and infiltrating leukocytes in the ischemic heart. Loss of Clec4e signaling is associated with reduced acute cardiac injury, neutrophil infiltration, and infarct size. Reduced myocardial injury in Clec4e–/– translates into significantly improved LV structural and functional remodeling at 4 weeks’ follow-up. The early transcriptome of LV tissue from Clec4e–/– mice versus wild-type mice reveals significant upregulation of transcripts involved in myocardial metabolism, radical scavenging, angiogenesis, and extracellular matrix organization. Therefore, targeting CLEC4E in the early phase of ischemia-reperfusion injury is a promising therapeutic strategy to modulate myocardial inflammation and enhance repair after ischemia-reperfusion injury.
Databáze: OpenAIRE
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