E-PROT-62
Ontology highlight
ABSTRACT:
TISSUE(S): Left Cardiac Atrium, Heart Left Ventricle, Right Cardiac Atrium
PROVIDER: E-PROT-62 | ExpressionAtlas | 2022-01-10
REPOSITORIES: ExpressionAtlas
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Project description:Genetic and genomic research has greatly advanced our understanding of heart disease; yet a comprehensive map of the protein landscape of living human hearts is still lacking. Here we set out to identify the molecular basis of functional differences between human cardiac chambers by comprehensive protein expression quantification from samples collected in vivo by high-resolution mass spectrometry. Cardiac biopsies of right atria (RA), left atria (LA) and left ventricle (LV) were obtained from seven humans undergoing open chest surgery and analyzed by high-resolution mass spectrometry. We identify hundreds of proteins with a chamber specific expression pattern, supporting the different functional roles of the cardiac chambers, enabling identification of chamber specific drug targets, and offering novel links between genomic data and the mechanisms of disease.
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Project description:Quantitative in vivo analyses reveal a complex pharmacogenomic landscape in lung adenocarcinoma
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Project description:Cardiopoietic stem cells are in advanced clinical testing for ischemic heart failure. To profile their uncharted molecular influence on recipient hearts, systems proteomics was applied in a chronic murine model of infarction randomized with and without human cardiopoietic stem cell treatment. Four biological replicates are included from each of three separate groups, Control (Ctrl, n=4), myocardial infarction without treatment (MI, n=4), and MI with cardiopoietic stem cell treatment (CP, n=4). Athymic nude male mice (2-3 months of age) underwent left anterior descending coronary artery ligation (70-min occlusion followed by reperfusion). ST elevation on the electrocardiogram confirmed MI. Four weeks post-MI, animals were randomized into cohorts without (MI, n=4) or with (CP, n=4) cell therapy. Human CP cells were generated from bone marrow derived mesenchymal stem cells using an established cardiopoiesis protocol. Media (15 µL), with or without CP cells (600,000 cells/heart), were epicardially delivered in infarcted left ventricles.
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Project description:Left ventricular mass (LVM) and cardiac gene expression are complex traits regulated by factors both intrinsic and extrinsic to the heart. To dissect the major determinants of LVM, we combined expression quantitative trait locus1 and quantitative trait transcript (QTT) analyses of the cardiac transcriptome in the rat. Using these methods and in vitro functional assays, we identified osteoglycin (Ogn) as a major candidate regulator of rat LVM, with increased Ogn protein expression associated with elevated LVM. We also applied genome-wide QTT analysis to the human heart and observed that, out of 22,000 transcripts, OGN transcript abundance had the highest correlation with LVM. We further confirmed a role for Ogn in the in vivo regulation of LVM in Ogn knockout mice. Taken together, these data implicate Ogn as a key regulator of LVM in rats, mice and humans, and suggest that Ogn modifies the hypertrophic response to extrinsic factors such as hypertension and aortic stenosis. Experiment Overall Design: 7 cardiac biopsies from control patients and 20 cardiac biopsies from aortic stenosis patients
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