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(Circulation Research. 2004;94:860.)
© 2004 American Heart Association, Inc.

Editorials

Titin and the Developing Heart

John S. Walker, Pieter P. de Tombe

From the Center for Cardiovascular Research, University of Illinois at Chicago, Chicago, Ill.

Correspondence to Pieter P. de Tombe, Department of Physiology and Biophysics, 835 S Wolcott Ave MC 901, University of Illinois at Chicago, Chicago, IL 60612. E-mail pdetombe@uic.edu

See related articles, pages 967–975 and Circ Res. 2004;94:505–513

Key Words: connectin • compliance • fetal • neonatal

An extract of the first 250 words of the full text is provided, because this article has no abstract.

During gestation, the mammalian heart operates under very different loading conditions than those seen during adult life. Ensuring that cardiac output is sufficient at the low filling pressures found in the fetal circulation requires mechanical strategies and protein complements different from those seen in the adult.

The studies by Opitz et al,¹ in this issue of Circulation Research, and Lahmers et al,² published recently in this journal, provide some clues as to the molecular basis of these strategies. Both studies examined the developing heart and found correlations between the expression of titin isoforms and the increased stiffness of the myocardium as the organism progressed from fetus through neonate to adult.

The pattern of findings is remarkably consistent across both studies and, despite differences with earlier claims of a less compliant fetal heart, leads to the conclusion that the fetal sarcomere is more compliant than the adult and that this is in large part due to the expression of particular isoforms of titin. But why is a more compliant titin isoform beneficial to the fetus?

Titin

We will briefly review the properties of titin here. Primary sources may be found by consulting recent reviews.^3–9

Titin, also known as connectin, is a relatively recently discovered giant protein (3 to 4 MDa ) that is the third most abundant protein in striated muscle, forming up to 10% of the total protein content of the cell. Titin extends half the length of the sarcomere from the Z-disc through the I-band and A-band to the . . . [Full Text of this Article]