title: Elastogenesis at the onset of human cardiac valve development.
abstract: Semilunar valve leaflets have a well-described trilaminar histoarchitecture, with a sophisticated elastic fiber network. It was previously proposed that elastin-containing fibers play a subordinate role in early human cardiac valve development; however, this assumption was based on data obtained from mouse models and human second and third trimester tissues. Here, we systematically analyzed tissues from human fetal first (4-12 weeks) and second (13-18 weeks) trimester, adolescent (14-19 years) and adult (50-55 years) hearts to monitor the temporal and spatial distribution of elastic fibers, focusing on semilunar valves. Global expression analyses revealed that the transcription of genes essential for elastic fiber formation starts early within the first trimester. These data were confirmed by quantitative PCR and immunohistochemistry employing antibodies that recognize fibronectin, fibrillin 1, 2 and 3, EMILIN1 and fibulin 4 and 5, which were all expressed at the onset of cardiac cushion formation (~week 4 of development). Tropoelastin/elastin protein expression was first detectable in leaflets of 7-week hearts. We revealed that immature elastic fibers are organized in early human cardiovascular development and that mature elastin-containing fibers first evolve in semilunar valves when blood pressure and heartbeat accelerate. Our findings provide a conceptual framework with the potential to offer novel insights into human cardiac valve development and disease.
authors: University Women's Hospital Tübingen and Inter-University Centre for Medical Technology Stuttgart-Tübingen (IZST), Eberhard Karls University, 72076 Tübingen, Germany..
authors: Miriam
authors: M
authors: Votteler
authors: Daniel A Carvajal
authors: DA
authors: Berrio
authors: Alexander
authors: A
authors: Horke
authors: Laetitia
authors: L
authors: Sabatier
authors: Dieter P
authors: DP
authors: Reinhardt
authors: Ali
authors: A
authors: Nsair
authors: Elena
authors: E
authors: Aikawa
authors: Katja
authors: K
authors: Schenke-Layland
mesh_terms: D000293:Adolescent; D004548:Elasticity; D004549:Elastin / Q000096:biosynthesis / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006351:Heart Valves / Q000196:embryology*; D006801:Humans; D008875:Middle Aged; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011262:Pregnancy Trimester, Second; D013997:Time Factors; D014333:Tropoelastin / Q000096:biosynthesis / Q000378:metabolism; D055815:Young Adult
chemical_list: D014333:Tropoelastin; D004549:Elastin
keywords: Elastic fibers; Elastin; Extracellular matrix; Heart; Heart valves
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