Serviço de Fisiologia, Faculdade de Medicina, Universidade do Porto, Portugal.
Arq Bras Cardiol. 2011 Apr;96(4):332-9. doi: 10.1590/s0066-782x2011005000023. Epub 2011 Feb 25.
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.
肌联蛋白是一种巨大的肌节蛋白，从 Z 线延伸到 M 线。由于其位置，它代表了一个重要的生物力学传感器，在维持肌节结构完整性方面起着关键作用。肌联蛋白作为一种“双向弹簧”，在长度发生变化时调节肌节长度并对被动张力进行适当调整。因此，它不仅决定了心室僵硬和舒张功能，还调节了心肌的收缩功能，调制了 Frank-Starling 机制。心肌表达这种大分子的两种同工型：N2B 更僵硬，N2BA 同工型更有弹性。两种肌联蛋白同工型的相对表达的改变或其磷酸化状态的改变与几种疾病的病理生理学有关，如舒张性心力衰竭、扩张型心肌病、缺血性心肌病和主动脉瓣狭窄。本研究的目的是简要描述肌联蛋白的结构和位置，它与不同心肌病的关系，并了解这种大分子的改变如何影响舒张性心力衰竭的病理生理学，强调操纵这种大分子的治疗潜力。
