title: Developmental control of titin isoform expression and passive stiffness in fetal and neonatal myocardium.
abstract: Developmental changes in contractile behavior are known to occur during fetal and postnatal heart development. In this study, we examined whether adaptations take place in titin. A range of species was used to evaluate titin isoform expression and altered function during cardiac muscle development. A novel titin exon microarray that allows all 363 titin exons to be monitored simultaneously was used for transcript studies. Results reveal expression of fetal titin isoforms, characterized by additional spring elements both in the tandem Ig and PEVK region of the molecule. At the protein level, the fetal cardiac isoform predominates in fetal and neonatal myocardium and gradually disappears during postnatal development with a time course that varies in different species. Passive myocardium, contrary to previous reports, was found to be less stiff in the neonate than in the adult. This can be explained by the unique spring composition of fetal cardiac titin expressed by the neonate. Changes in titin expression are likely to impact functional transitions and diastolic filling behavior during development of the heart.
authors.affiliation: Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman, Wash 99164, USA.
authors.forename: Sunshine
authors.initials: S
authors.lastname: Lahmers
authors.forename: Yiming
authors.initials: Y
authors.lastname: Wu
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Call
authors.forename: Siegfried
authors.initials: S
authors.lastname: Labeit
authors.forename: Henk
authors.initials: H
authors.lastname: Granzier
mesh_terms: D000375:Aging / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D064211:Connectin; D016384:Consensus Sequence; D004548:Elasticity; D005091:Exons / Q000235:genetics; D005318:Fetal Heart / Q000378:metabolism* / Q000502:physiology; D005326:Fetal Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000254:growth & development / Q000502:physiology; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D020033:Protein Isoforms / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D011494:Protein Kinases / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013552:Swine; D014158:Transcription, Genetic
chemical_list: D064211:Connectin; D005326:Fetal Proteins; D009124:Muscle Proteins; D020033:Protein Isoforms; C577285:TTN protein, human; D011494:Protein Kinases