Myocardial ischemia-reperfusion enhances transcriptional expression of endothelin-1 and vasoconstrictor ETB receptors via the protein kinase MEK-ERK1/2 signaling pathway in rat

Autor: Lars S Kruse, Lars Edvinsson, Karin Warfvinge, Gry Freja Skovsted, Anne-Sofie Grell, Lukas Adrian Berchtold
Rok vydání: 2017
Předmět:
Male
0301 basic medicine
Critical Care and Emergency Medicine
Myocardial Infarction
Gene Expression
lcsh:Medicine
030204 cardiovascular system & hematology
Pharmacology
Vascular Medicine
Rats
Sprague-Dawley
Random Allocation
0302 clinical medicine
Cell Signaling
Ischemia
Medicine and Health Sciences
Vasoconstrictor Agents
Enzyme Inhibitors
Extracellular Signal-Regulated MAP Kinases
lcsh:Science
Receptor
Coronary Arteries
Multidisciplinary
Protein Kinase Signaling Cascade
Endothelin-1
Heart
Vasospasm
Arteries
Receptor
Endothelin B
Signaling Cascades
Precipitation Techniques
medicine.anatomical_structure
cardiovascular system
Cardiology
Anatomy
medicine.symptom
Endothelin receptor
Research Article
Signal Transduction
Artery
medicine.medical_specialty
MAP Kinase Signaling System
Myocardial Reperfusion Injury
Viper Venoms
Research and Analysis Methods
03 medical and health sciences
Internal medicine
Nitriles
Genetics
Butadienes
medicine
Immunoprecipitation
Animals
Immunohistochemistry Techniques
business.industry
Myocardium
lcsh:R
Biology and Life Sciences
Cell Biology
medicine.disease
Endothelin 1
Rats
Histochemistry and Cytochemistry Techniques
Coronary arteries
030104 developmental biology
Reperfusion
Cardiovascular Anatomy
Immunologic Techniques
Blood Vessels
lcsh:Q
business
Vasoconstriction
Zdroj: Skovsted, G F, Kruse, L S, Berchtold, L A, Grell, A-S, Warfvinge, K & Edvinsson, L 2017, ' Myocardial ischemia-reperfusion enhances transcriptional expression of endothelin-1 and vasoconstrictor ET B receptors via the protein kinase MEK-ERK1/2 signaling pathway in rat ', PLOS ONE, vol. 12, no. 3, e0174119 . https://doi.org/10.1371/journal.pone.0174119
PLoS ONE, Vol 12, Iss 3, p e0174119 (2017)
PLoS ONE
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0174119
Popis: Background: Coronary artery remodelling and vasospasm is a complication of acute myocardial ischemia and reperfusion. The underlying mechanisms are complex, but the vasoconstrictor peptide endothelin-1 is suggested to have an important role. This study aimed to determine whether the expression of endothelin-1 and its receptors are regulated in the myocardium and in coronary arteries after experimental ischemia-reperfusion. Furthermore, we evaluated whether treatment with a specific MEK1/2 inhibitor, U0126, modified the expression and function of these proteins. Methods and findings: Sprague-Dawley rats were randomly divided into three groups: sham-operated, ischemiareperfusion with vehicle treatment and ischemia-reperfusion with U0126 treatment. Ischemia was induced by ligating the left anterior descending coronary artery for 30 minutes followed by reperfusion. U0126 was administered before ischemia and repeated 6 hours after start of reperfusion. The contractile properties of isolated coronary arteries to endothelin-1 and sarafotoxin 6c were evaluated using wire-myography. The gene expression of endothelin-1 and endothelin receptors were measured using qPCR. Distribution and localization of proteins (pERK1/2, prepro-endothelin-1, endothelin-1, and endothelin ETA and ETB receptors) were analysed by Western blot and immunohistochemistry. We found that pERK1/2 was significantly augmented in the ischemic area 3 hours after ischemia-reperfusion; this correlated with increased ETB receptor and ET-1 gene expressions in ischemic myocardium and in coronary arteries. ETB receptor-mediated vasoconstriction was observed to be increased in coronary arteries 24 hours after ischemia-reperfusion. Treatment with U0126 reduced pERK1/2, expression of ET-1 and ETB receptor, and ETB receptor-mediated vasoconstriction. Conclusions: These findings suggest that the MEK-ERK1/2 signaling pathway is important for regulating endothelin-1 and ETB receptors in myocardium and coronary arteries after ischemia-reperfusion in the ischemic region. Inhibition of the MEK-ERK1/2 pathway may provide a novel target for reducing ischemia-reperfusion damage in the heart.
Databáze: OpenAIRE
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