viral-transgene-expression-rodent-hearts-assessment-cardiac

Viral Transgene Expression in Rodent Hearts and the Assessment of Cardiac Arrhythmia Risk

Heart disease is the leading cause of morbidity and mortality worldwide. Due to the ease of handling&#160;and abundance of transgenic strains, rodents ...

University of Ottawa Heart Institute

University of Ottawa

A novel method to measure vascular inflammation by [18F]fluorodeoxyglucose PET/computed tomography scanning of the aorta.

Myocardial infarction and heart failure are associated with reduced voltage-gated Na current (I) that promotes arrhythmias and sudden deaths. We have previously shown that the Wnt/β-catenin signalling (Wnt signalling), which is active in heart disease, reduces cardiac I, suggesting that Wnt signalling may be a potential therapeutic target. However, because Wnt signalling is required for the homeostasis of many noncardiac tissues, administration of Wnt inhibitors to heart patients would cause significant side effects. The present study aims to elucidate the molecular mechanisms of cardiac I inhibition by Wnt, which would identify cardiac-specific therapeutic targets.

Direct and Indirect Suppression of Scn5a Gene Expression Mediates Cardiac Na Channel Inhibition by Wnt Signalling.

Survivors of community-acquired pneumonia (CAP) are at increased risk of cardiovascular disease, cognitive and functional decline, and death, but the mechanisms remain unknown.

Persistent Lung Inflammation After Clinical Resolution of Community-Acquired Pneumonia as Measured by FDG-PET/CT Imaging.

Wnt/β-catenin signaling is activated in the heart after myocardial infarction (MI). This study aims to investigate if β-catenin deletion affects post-MI ion channel gene alterations and ventricular tachycardias (VT). MI was induced by permanent ligation of left anterior descending artery in wild-type (WT) and cardiomyocyte-specific β-catenin knockout (KO) mice. KO mice showed reduced susceptibility to VT (18% vs. 77% in WT) at 8 weeks after MI, associated with reduced scar size and attenuated chamber dilation. qPCR analyses of both myocardial tissues and purified cardiomyocytes demonstrated upregulation of Wnt pathway genes in border and infarct regions after MI, including Wnt ligands (such as Wnt4) and receptors (such as Fzd1 and Fzd2). At 1 week after MI, cardiac sodium channel gene (Scn5a) transcript was reduced in WT but not in KO hearts, consistent with previous studies showing Scn5a inhibition by Wnt/β-catenin signaling. At 8 weeks after MI when Wnt genes have declined, Scn5a returned to near sham levels and K channel gene downregulations were not different between WT and KO mice. This study demonstrated that VT susceptibility in the chronic phase after MI is reduced in mice with cardiomyocyte-specific β-catenin deletion primarily through attenuated structural remodeling, but not ion channel gene alterations.

Cardiomyocyte-specific deletion of β-catenin protects mouse hearts from ventricular arrhythmias after myocardial infarction.

This study aimed to evaluate markers of systemic as well as imaging markers of inflammation in the ascending aorta, bone marrow, and spleen measured by 18F-FDG PET/CT, in HIV+ patients at baseline and following therapy with rosuvastatin.

Article	Year
A novel method to measure vascular inflammation by [18F]fluorodeoxyglucose PET/computed tomography scanning of the aorta. Nuclear medicine communications\| PubMed ID: 31517809	2019
Direct and Indirect Suppression of Scn5a Gene Expression Mediates Cardiac Na Channel Inhibition by Wnt Signalling. The Canadian journal of cardiology\| PubMed ID: 32046907	2020
Persistent Lung Inflammation After Clinical Resolution of Community-Acquired Pneumonia as Measured by FDG-PET/CT Imaging. Chest\| PubMed ID: 33667494	2021
Cardiomyocyte-specific deletion of β-catenin protects mouse hearts from ventricular arrhythmias after myocardial infarction. Scientific reports\| PubMed ID: 34489488	2021
Anti-inflammatory effect of rosuvastatin in patients with HIV infection: An FDG-PET pilot study. Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology\| PubMed ID: 34820771	2021

Jerry Wang

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