The full cardiac G protein-coupled receptor repertoire reveals chamber-specific expression patterns
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ABSTRACT: Cardiac function is regulated by many hormones and neurotransmitters which exert their physiological effects through the activation of G protein-coupled receptors (GPCRs). Here, we quantified the expression of 395 endoGPCRs (all GPCRs excluding taste and odorant receptors) in male mouse right and left atria and ventricles by using high-throughput real-time RT-PCR and focused on the 135 most highly expressed transcripts. No cardiac functional data is available for almost half of these receptors. Cluster analysis allowed us to link GPCR expression patterns to cardiac function. Indeed, ventricles and atria are both contractile; however, the latter, and especially the right atrium, are central to the generation and regulation of cardiac rhythm. Accordingly, the right atrium exhibited the most specific signature whereas the vast majority of GPCRs found in ventricles were evenly expressed in both the right and left chambers. RT-PCR data were confirmed at the protein level for six selected transcripts (ETA, EP1, PAR1, Sfrp1, CCR2 and AT1a) and at the functional level in isolated mouse ventricular cardiomyocytes for the glutamate metabotropic receptor 1b.
Project description:Two wild-type mouse strains (Swiss Agouti and MF1) were investigated regarding the mRNA expression patterns of their left and right atria at 12 months of age. Eight samples of each strain, four with left atrium and four with right atrium examined.
Project description:Atria and ventricles exhibit distinct molecular profiles that produce structural and functional differences between the two cardiac compartments. However, factors that determine these differences remain largely undefined. Cardiomyocyte-specific COUP- TFII ablation produces ventricularized atria that exhibit ventricle-like action potentials, increased cardiomyocyte size, and development of extensive T-tubules. We used microarrays to examine the molecular profile of cardiomyocyte-specific COUP-TFII knockout adult atria in comparison with that of normal atria. We extracted RNA from mutant right atria, control right atria and control ventricles from 2 months old adult mice, followed by gene expression profiling using Affymetrix microarrays.
Project description:Background: Lamins A/C (encoded by the LMNA gene) can lead to dilated cardiomyopathy (DCM). Objectives: This study sought to undertake proteomic analysis of myocardial tissue to explore the postgenomic phenotype of end-stage lamin heart disease. Methods: Consecutive patients with end-stage lamin heart disease (LMNA-group, n=7) and ischaemic DCM (ICM-group, n=7) undergoing heart transplantation were enrolled. Samples were obtained from left atrium(LA), left ventricle(LV), right atrium(RA), right ventricle(RV) and interventricular septum(IVS). Liquid chromatography combined with mass-spectrometry was used for protein quantification. We compared protein concentrations in cardiac samples between LMNA and ICM groups. Proteins were considered differentially abundant if the quantitative difference was 1.5-fold and corrected p-value <0.05 at a false discovery rate of 0.01. Gene ontology(GO) enrichment analysis explored the related biological processes. Results: 4,247 proteins were identified in LMNA and ICM samples, of which 633 were differentially abundant in LA, 39 in LV, 181 in RA, 52 in RV, and 85 in IVS. Abundance of lamin A/C was reduced but lamin B (LMNB) increased in LMNA LA/RA tissue compared to ICM, but not in LV/RV. Transthyretin was more abundant in the LV/RV of LMNA compared to ICM while sarcomeric proteins such as titin and cardiac myosin heavy chain were generally reduced in RA/LA of LMNA. Protein expression profiling and GO enrichment analysis revealed sarcopenia, extracellular matrix(ECM) remodeling, deficient myocardial energetics, redox imbalances, and abnormal calcium handling in LMNA samples. Conclusion: Lamin heart disease is a biventricular and biatrial disease, characterized by sarcopenia, aberrant metabolism, and ECM remodeling. LMNB and transthyretin were unexpectedly abundant in the atria and ventricles respectively of patients with end-stage lamin heart disease potentially hinting to the possibility of compensatory responses.
Project description:We created a fetal lamb model of hypoplastic left heart syndrome (HLHS), by implanting coils in the left atrium in mid-gestation. We performed bulk RNA sequencing of left ventricles (LV), right ventricles (RV), ascending aortae (AAo) and pulmonary arteries (PA). Single nucleus RNA sequencing was performed on LV free wall tissue (n = 4 coiled samples, n = 3 controls).
Project description:We created a fetal lamb model of hypoplastic left heart syndrome (HLHS), by implanting coils in the left atrium in mid-gestation. We performed bulk RNA sequencing of left ventricles (LV), right ventricles (RV), ascending aortae (AAo) and pulmonary arteries (PA). Single nucleus RNA sequencing was performed on LV free wall tissue (n = 4 coiled samples, n = 3 controls).
Project description:Using Multiome and previously published sc/snRNA-seq data, we studied eight anatomical regions of the human heart including left and right ventricular free walls (LV and RV), left and right atria (LA and RA), left ventricular apex (AX), interventricular septum (SP), sino-atrial node (SAN) and atrioventricular node (AVN). For the first time, we profile the cells of the human cardiac conduction system, revealing their distinctive repertoire of ion channels, G-protein coupled receptors and cell-cell interactions. We map the identified cells to spatial transcriptomic data to discover cellular niches within the eight regions of the heart.
Project description:Using Multiome and previously published sc/snRNA-seq data, we studied eight anatomical regions of the human heart including left and right ventricular free walls (LV and RV), left and right atria (LA and RA), left ventricular apex (AX), interventricular septum (SP), sino-atrial node (SAN) and atrioventricular node (AVN). For the first time, we profile the cells of the human cardiac conduction system, revealing their distinctive repertoire of ion channels, G-protein coupled receptors and cell-cell interactions. We map the identified cells to spatial transcriptomic data to discover cellular niches within the eight regions of the heart.
Project description:Using Multiome and previously published sc/snRNA-seq data, we studied eight anatomical regions of the human heart including left and right ventricular free walls (LV and RV), left and right atria (LA and RA), left ventricular apex (AX), interventricular septum (SP), sino-atrial node (SAN) and atrioventricular node (AVN). For the first time, we profile the cells of the human cardiac conduction system, revealing their distinctive repertoire of ion channels, G-protein coupled receptors and cell-cell interactions. We map the identified cells to spatial transcriptomic data to discover cellular niches within the eight regions of the heart.
Project description:A comparison of human cardiac gene expression profile in paired samples of right atrium and left ventricle extracted in vivo<br><br>
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.