Published online before print January 5, 2004, doi: 10.1161/01.RES.0000115522.52554.86
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on November 3, 2003
Revised on December 17, 2003
Accepted on December 19, 2003
Developmental Control of Titin Isoform Expression and Passive Stiffness in Fetal and Neonatal Myocardium
Sunshine Lahmers ;
From the Departments of Veterinary and Comparative Anatomy, Pharmacology and Physiology (S. Lahmers, Y.W., H.G.) and Veterinary Microbiology and Pathology (D.R.C.), Washington State University, Pullman, Wash; and Anästhesiologie und Operative Intensivmedizin (S. Labeit), Universitätsklinikum Mannheim, Mannheim, Germany.
* To whom correspondence should be addressed. E-mail: granzier{at}wsunix.wsu.edu.
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.
Key words: diastole • compliance • filling • connectin • microarray
This article has been cited by other articles:
 |
|
 |
|
  W. A. Linke Sense and stretchability: The role of titin and titin-associated proteins in myocardial stress-sensing and mechanical dysfunction Cardiovasc Res, March 1, 2008; 77(4): 637 - 648. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Kruger, C. Sachse, W. H. Zimmermann, T. Eschenhagen, S. Klede, and W. A. Linke Thyroid Hormone Regulates Developmental Titin Isoform Transitions via the Phosphatidylinositol-3-Kinase/ AKT Pathway Circ. Res., February 29, 2008; 102(4): 439 - 447. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Granzier, M. Radke, J. Royal, Y. Wu, T. C. Irving, M. Gotthardt, and S. Labeit Functional genomics of chicken, mouse, and human titin supports splice diversity as an important mechanism for regulating biomechanics of striated muscle Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2007; 293(2): R557 - R567. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Takata, S. Uchiyama, N. Nakamura, S. Nakashima, S. Kobayashi, T. Sone, S. Kimura, S. Lahmers, H. Granzier, S. Labeit, et al. A comparative proteome analysis of human metaphase chromosomes isolated from two different cell lines reveals a set of conserved chromosome-associated proteins Genes Cells, March 1, 2007; 12(3): 269 - 284. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Seeley, W. Huang, Z. Chen, W. O. Wolff, X. Lin, and X. Xu Depletion of Zebrafish Titin Reduces Cardiac Contractility by Disrupting the Assembly of Z-Discs and A-Bands Circ. Res., February 2, 2007; 100(2): 238 - 245. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Kruger, T. Kohl, and W. A. Linke Developmental changes in passive stiffness and myofilament Ca2+ sensitivity due to titin and troponin-I isoform switching are not critically triggered by birth Am J Physiol Heart Circ Physiol, August 1, 2006; 291(2): H496 - H506. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Notomi, G. Srinath, T. Shiota, M. G. Martin-Miklovic, L. Beachler, K. Howell, S. J. Oryszak, D. G. Deserranno, A. D. Freed, N. L. Greenberg, et al. Maturational and Adaptive Modulation of Left Ventricular Torsional Biomechanics: Doppler Tissue Imaging Observation From Infancy to Adulthood Circulation, May 30, 2006; 113(21): 2534 - 2541. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Weinert, N. Bergmann, X. Luo, B. Erdmann, and M. Gotthardt M line-deficient titin causes cardiac lethality through impaired maturation of the sarcomere J. Cell Biol., May 22, 2006; 173(4): 559 - 570. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. C. Ottenheijm, L. M. A. Heunks, T. Hafmans, P. F. M. van der Ven, C. Benoist, H. Zhou, S. Labeit, H. L. Granzier, and P. N. R. Dekhuijzen Titin and Diaphragm Dysfunction in Chronic Obstructive Pulmonary Disease Am. J. Respir. Crit. Care Med., March 1, 2006; 173(5): 527 - 534. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. C. Lim and D. B. Sawyer Modulation of Cardiac Function: Titin Springs into Action J. Gen. Physiol., February 28, 2005; 125(3): 249 - 252. [Full Text] [PDF]
|
|
|
|
 |
|
 A. Sarkar, S. Caamano, and J. M. Fernandez The Elasticity of Individual Titin PEVK Exons Measured by Single Molecule Atomic Force Microscopy J. Biol. Chem., February 25, 2005; 280(8): 6261 - 6264. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Fujita, D. Labeit, B. Gerull, S. Labeit, and H. L. Granzier Titin isoform-dependent effect of calcium on passive myocardial tension Am J Physiol Heart Circ Physiol, December 1, 2004; 287(6): H2528 - H2534. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Makarenko, C.A. Opitz, M.C. Leake, C. Neagoe, M. Kulke, J.K. Gwathmey, F. del Monte, R.J. Hajjar, and W.A. Linke Passive Stiffness Changes Caused by Upregulation of Compliant Titin Isoforms in Human Dilated Cardiomyopathy Hearts Circ. Res., October 1, 2004; 95(7): 708 - 716. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. LeWinter Titin Isoforms in Heart Failure: Are There Benefits to Supersizing? Circulation, July 13, 2004; 110(2): 109 - 111. [Full Text] [PDF]
|
|
|
|
|
|
S. F. Nagueh, G. Shah, Y. Wu, G. Torre-Amione, N. M.P. King, S. Lahmers, C. C. Witt, K. Becker, S. Labeit, and H. L. Granzier Altered Titin Expression, Myocardial Stiffness, and Left Ventricular Function in Patients With Dilated Cardiomyopathy Circulation, July 13, 2004; 110(2): 155 - 162. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-C. Han, K. J. Austin, P. W. Nathanielsz, S. P. Ford, M. J. Nijland, and T. R. Hansen Maternal nutrient restriction alters gene expression in the ovine fetal heart J. Physiol., July 1, 2004; 558(1): 111 - 121. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Kass, J. G.F. Bronzwaer, and W. J. Paulus What Mechanisms Underlie Diastolic Dysfunction in Heart Failure? Circ. Res., June 25, 2004; 94(12): 1533 - 1542. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Walker and P. P. de Tombe Titin and the Developing Heart Circ. Res., April 16, 2004; 94(7): 860 - 862. [Full Text] [PDF]
|
|