The Role of Titin in the Modulation of Cardiac Function and Its Pathophysiological Implications

• Type: Article in International Scientific Journal
• Date: 2011

Authors

Castro Ferreira, R (Author) Other; Fontes Carvalho, R (Author) Other; Falcao Pires, I (Author) FMUP; Leite-Moreira AF (Author) FMUP

Journal

Title: Arquivos Brasileiros de Cardiologia

Vol. 96 No. 4

Pages: 332-339

ISSN: 0066-782X

Publisher: Sociedad Brasileira De Cardiologia

Indexing

ISI Web of Knowledge - 13 Citations

Scopus - 13 Citations

Pubmed / Medline

Other information

Authenticus ID: P-002-SJT

DOI: 10.1590/s0066-782x2011005000023

Abstract (EN): Titin is a giant sarcomeric protein that extends from the Z-line to the M-line. Due to its location, it represents an important biomechanical sensor, which has a crucial role in the maintenance of the sarcomere structural integrity. Titin works as a "bidireactional spring" that regulates the sarcomeric length and performs adequate adjustments of passive tension whenever the length varies. Therefore, it determines not only ventricular rigidity and diastolic function, but also systolic cardiac function, modulating the Frank-Starling mechanism. The myocardium expresses two isoforms of this macromolecule: the N2B, more rigid and the isoform N2BA, more compliant. The alterations in the relative expression of the two titin isoforms or alterations in their state of phosphorylation have been implicated in the pathophysiology of several diseases, such as diastolic heart failure, dilated cardiomyopathy, ischemic cardiomyopathy and aortic stenosis. The aim of this study is to describe, in brief, the structure and location of titin, its association with different cardiomyopathies and understand how alterations in this macromolecule influence the pathophysiology of diastolic heart failure, emphasizing the therapeutic potential of the manipulation of this macromolecule.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8