title: Spatial expression of components of a calcitonin receptor-like receptor (CRL) signalling system (CRL, calcitonin gene-related peptide, adrenomedullin, adrenomedullin-2/intermedin) in mouse and human heart valves.
abstract: Heart valves are highly organized structures determining the direction of blood flow through the heart. Smooth muscle cells within the valve are thought to play an active role during the heart cycle, rather than being just passive flaps. The mature heart valve is composed of extracellular matrix (ECM), various differentiations of valvular interstitial cells (VIC), smooth muscle cells and overlying endothelium. VIC are important for maintaining the structural integrity of the valve, thereby affecting valve function and ECM remodelling. Accumulating evidence suggests an important role of calcitonin receptor-like receptor (CRL) signalling in preventing heart damage under several pathological conditions. Thus we investigate the existence of a putative CRL signalling system in mouse and human heart valves by real-time RT-PCR, laser-assisted microdissection, immunofluorescence and NADPH-diaphorase histochemistry. Mouse and human heart valves expressed mRNAs for the CRL ligands adrenomedullin (AM), adrenomedullin-2 (AM-2) and calcitonin gene-related peptide (CGRP) and for their receptor components, i.e., CRL and receptor-activity-modifying proteins 1-3. Immunofluorescence analysis revealed AM-, AM-2- and CRL-immunolabelling in endothelial cells and VIC, whereas CGRP immunoreactivity was restricted to nerve fibres and some endothelial cells. Nitric oxide synthase activity, as demonstrated by NADPH-diaphorase histochemistry, was shown mainly in valvular endothelial cells in mice, whereas in human aortic valves, VIC and smooth muscle cells were positive. Our results showed the presence of an intrinsic AM/AM-2/CGRP signalling system in murine and human heart valves with distinct cellular localization, suggesting its involvement in the regulation of valve stiffness and ECM production and turnover.
authors.affiliation: Institute for Anatomy and Cell Biology, Excellence Cluster Cardio-Pulmonary System, German Center for Lung Research (DZL), Justus-Liebig University, Giessen, Germany. uwe.pfeil@anatomie.med.uni-giessen.de.
authors.forename: Uwe
authors.initials: U
authors.lastname: Pfeil
authors.affiliation: Institute for Anatomy and Cell Biology, Excellence Cluster Cardio-Pulmonary System, German Center for Lung Research (DZL), Justus-Liebig University, Giessen, Germany.|Faculty of Health Science, Linkoping University, Linkoping, Sweden.
authors.forename: Subhashini
authors.initials: S
authors.lastname: Bharathala
authors.affiliation: Department of Neurology, King Saud University, Riyadh, Kingdom of Saudi Arabia.
authors.forename: Ghulam
authors.initials: G
authors.lastname: Murtaza
authors.affiliation: Institute for Anatomy and Cell Biology, Excellence Cluster Cardio-Pulmonary System, German Center for Lung Research (DZL), Justus-Liebig University, Giessen, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Mermer
authors.affiliation: Institute for Anatomy and Cell Biology, Excellence Cluster Cardio-Pulmonary System, German Center for Lung Research (DZL), Justus-Liebig University, Giessen, Germany.
authors.forename: Tamara
authors.initials: T
authors.lastname: Papadakis
authors.affiliation: Department of Cardiovascular Surgery, University Hospital Giessen and Marburg, Giessen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Boening
authors.affiliation: Institute for Anatomy and Cell Biology, Excellence Cluster Cardio-Pulmonary System, German Center for Lung Research (DZL), Justus-Liebig University, Giessen, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kummer
mesh_terms: D053607:Adrenomedullin / Q000378:metabolism*; D000818:Animals; D000918:Antibody Specificity; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D058286:Calcitonin Receptor-Like Protein / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism; D006351:Heart Valves / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D056885:Interstitial Cells of Cajal / Q000166:cytology / Q000378:metabolism; D061346:Laser Capture Microdissection; D008810:Mice, Inbred C57BL; D009412:Nerve Fibers / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D036361:Peptide Hormones / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: C484330:ADM2 protein, human; D058286:Calcitonin Receptor-Like Protein; D009479:Neuropeptides; D036361:Peptide Hormones; C514552:intermedin protein, mouse; D053607:Adrenomedullin; D019001:Nitric Oxide Synthase; D015740:Calcitonin Gene-Related Peptide
keywords: Adrenomedullin; Adrenomedullin-2; Calcitonin gene-related peptide; Calcitonin receptor-like receptor; Intermedin