Dataset Information

Cathepsin A Mediates Ventricular Remote Remodeling and Atrial Cardiomyopathy in Rats With Ventricular Ischemia/Reperfusion.

ABSTRACT: After myocardial infarction, remote ventricular remodeling and atrial cardiomyopathy progress despite successful revascularization. In a rat model of ventricular ischemia/reperfusion, pharmacological inhibition of the protease activity of cathepsin A initiated at the time point of reperfusion prevented extracellular matrix remodeling in the atrium and the ventricle remote from the infarcted area. This scenario was associated with preservation of more viable ventricular myocardium and the prevention of an arrhythmogenic and functional substrate for atrial fibrillation. Remote ventricular extracellular matrix remodeling and atrial cardiomyopathy may represent a promising target for pharmacological atrial fibrillation upstream therapy following myocardial infarction.

SUBMITTER: Hohl M

PROVIDER: S-EPMC6609908 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Cathepsin A Mediates Ventricular Remote Remodeling and Atrial Cardiomyopathy in Rats With Ventricular Ischemia/Reperfusion.

Hohl Mathias M Erb Katharina K Lang Lisa L Ruf Sven S Hübschle Thomas T Dhein Stefan S Linz Wolfgang W Elliott Adrian D AD Sanders Prashanthan P Zamyatkin Olesja O Böhm Michael M Schotten Ulrich U Sadowski Thorsten T Linz Dominik D

JACC. Basic to translational science 20190624 3

After myocardial infarction, remote ventricular remodeling and atrial cardiomyopathy progress despite successful revascularization. In a rat model of ventricular ischemia/reperfusion, pharmacological inhibition of the protease activity of cathepsin A initiated at the time point of reperfusion prevented extracellular matrix remodeling in the atrium and the ventricle remote from the infarcted area. This scenario was associated with preservation of more viable ventricular myocardium and the prevent ...[more]

PMID: 31312757

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Project description:AimsChemokine receptor 7 (CXCR7) exerts protective effects on the brain. MicroRNAs (miRNAs) are involved in cerebral ischemia/reperfusion (I/R) injury, but their involvement in CXCR7-mediated brain protection is unknown. In this study, we investigated the role of miRNAs in CXCR7-mediated brain protection.MethodsCXCR7 levels in peripheral blood samples from patients with acute ischemic stroke (AIS) and ischemic penumbra area brain tissues from middle cerebral artery occlusion (MCAO) rats after recanalization were measured. An miRNA microarray analysis was performed to examine the expression of miRNAs caused by CXCR7 knockdown in ischemic penumbra area brain tissue in middle cerebral artery occlusion-reperfusion rats and to predict corresponding downstream target genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed the most enriched pathways. A dual-luciferase reporter assay confirmed the direct regulation of miR-182 on the target gene TCF7L2. The correlation between TCF7L2 and CXCR7/miR-182 was verified using rescue assays.ResultsCXCR7 expression was upregulated in MCAO rats and mechanical thrombectomy patients with AIS compared to that in controls. The motor and sensory functions of MCAO rats with CXCR7 knockdown further decreased, and the infarct volume and cerebral edema increased. miRNA microarray data showed that seven miRNAs were differentially expressed after shRNA-CXCR7 treatment. The dual-luciferase reporter assay confirmed that miR-182 directly targeted the TCF7L2 gene. Rescue assays confirmed that TCF7L2 is downstream of CXCR7/miR-182. KEGG pathway analysis showed that the Hippo pathway may be a key pathway in CXCR7 upregulation and plays a role in protecting the brain after interventional surgery. Animal experiments have shown that CXCR7-mediated cerebral I/R injury promotes the phosphorylation of key molecules YAP and TAZ in the Hippo pathway.ConclusionCXCR7 protects against cerebral I/R injury, possibly via the miR-182/TCF7L2/Hippo pathway. These results indicate that CXCR7 affects cerebral ischemia-reperfusion injury through miRNA regulation and downstream pathways.

Dataset Information

Cathepsin A Mediates Ventricular Remote Remodeling and Atrial Cardiomyopathy in Rats With Ventricular Ischemia/Reperfusion.

Publications

Cathepsin A Mediates Ventricular Remote Remodeling and Atrial Cardiomyopathy in Rats With Ventricular Ischemia/Reperfusion.

Similar Datasets

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