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(Circulation. 2004;110:109-111.)
© 2004 American Heart Association, Inc.

Editorial

Titin Isoforms in Heart Failure

Are There Benefits to Supersizing?

Martin M. LeWinter, MD

From the University of Vermont, Burlington, Vt.

Correspondence to Cardiology Unit, Fletcher Allen Health Care, 111 Colchester Ave, Burlington, VT 05401. E-mail martin.lewinter@vtmednet.org

Key Words: Editorials • connectin • diastole • myocardium • ventricular function

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

Titin is a giant sarcomeric protein that functions as a complex, molecular spring. Its presence in the sarcomere of striated muscle was recognized in the 1980s,¹ but its functions have been appreciated only over the past decade, in considerable measure because of the efforts of Granzier, Labeit, Linke, and coworkers.^2–4 Earlier work by these investigators and others⁴ delineated the spring properties of titin and its role as the prime source of passive tension in the cardiomyocyte and, along with collagen, in myocardium. Titin also interacts and/or binds with a host of other proteins,⁴ including actin, a number of Z-disc proteins,⁵ obscurin,⁶ muscle LIM protein,⁴ and the group of muscle ankyrin repeat proteins.^4,7 These interactions suggest additional functions, and recent evidence indicates that titin directly modifies sarcomere shortening and has intriguing and potentially diverse roles in mechanical sensing and signaling pathways.⁴

See p 155

Titin Gene and Protein

Titin is encoded by a single gene containing 363 exons.⁸ Differential splicing results in two major isoforms, the shorter and stiffer N2B and the longer, more compliant N2BA.^4,8 N2BA titin has numerous fetal-neonatal variants, but most variation is lost in adult life. Titin is positioned within the sarcomere such that its N-terminal segments are anchored in the Z disc and its C-terminal segments are bound to the thick filament in the M-line region (see Figure 1 in Granzier and Labeit⁴). The N-terminal segment penetrating the Z-disc is capped by telethonin (T-cap), a protein that may have a role in mechanical signaling and maintenance of important structural . . . [Full Text of this Article]

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