Department of Pediatrics, Pediatric Cardiology Service, University of Catania, Via S Sofia 78, Catania, 95123, Italy.
Ital J Pediatr. 2012 Sep 12;38:41. doi: 10.1186/1824-7288-38-41.
It is well known that the natural history of chronic heart failure (CHF),regardless of age and aetiology,is characterized by progressive cardiac dysfunction refractory to conventional cardiokinetic, diuretic and peripheral vasodilator therapy. Several previous studies, both in animals and humans, showed that the key pathogenetic element of CHF negative clinical evolution is constituted by myocardial remodeling. This is a complex pathologic process of ultrastructural rearrangement of the heart induced by various neuro-humoral factors released by cardiac fibrocells in response to biomechanical stress connected to chronic haemodynamic overload. Typical features of myocardial remodeling are represented by cardiomyocytes hypertrophy and apoptosis, extracellular matrix alterations, mesenchymal fibrotic and phlogistic processes and by cardiac gene expression modifications with fetal genetic program reactivation. In the last years, increasing knowledge of subtle molecular and cellular mechanisms involved in myocardial remodeling has led to the discovery of some new potential therapeutic targets capable of inducing its regression. In this paper our attention is focused on the possible use of antiapoptotic and antifibrotic agents, and on the fascinating perspectives offered by the development of myocardial gene therapy and, in particular, by myocardial regenerative therapy.
众所周知，无论年龄和病因如何，慢性心力衰竭（CHF）的自然病程都以对传统的心肌动力、利尿剂和外周血管扩张剂治疗有抗性的进行性心脏功能障碍为特征。几项先前的动物和人类研究表明，CHF 阴性临床进展的关键发病因素是心肌重构。这是一种由心脏成纤维细胞在慢性血流动力学过载引起的生物力学应激下释放的各种神经激素因子诱导的心脏超微结构重排的复杂病理过程。心肌重构的典型特征包括心肌细胞肥大和凋亡、细胞外基质改变、间质纤维化和炎症过程，以及心脏基因表达的改变，从而重新激活胎儿遗传程序。近年来，对参与心肌重构的细微分子和细胞机制的认识不断增加，导致发现了一些新的潜在治疗靶点，这些靶点能够诱导其逆转。本文重点讨论了使用抗凋亡和抗纤维化药物的可能性，以及心肌基因治疗，特别是心肌再生治疗所带来的迷人前景。
