Molecular pathogenesis of myocardial remodeling and new potential therapeutic targets in chronic heart failure.
Molecular pathogenesis of myocardial remodeling and new potential therapeutic targets in chronic heart failure.
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DOI：
10.1186/1824-7288-38-41
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发表时间：
2012-09-12
影响因子：
3.6
通讯作者：
Sciacca P
中科院分区：
文献类型：
--
作者：
Distefano G;Sciacca P
众所周知，慢性心力衰竭(CHF)的自然病史，无论年龄和病因，都以进行性心功能障碍为特征，对传统的心动力、利尿剂和外周血管扩张剂治疗无效。先前在动物和人类中的研究表明，CHF临床阴性演变的关键致病因素是由心肌重构构成的。这是一个复杂的心脏超微结构重排的病理过程，由心脏纤维细胞在生物力学压力下释放的各种神经体液因子引起，与慢性血流动力学超负荷有关。心肌重塑的典型特征是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和胎儿遗传程序的重新激活。近年来，随着人们对心肌重塑相关分子和细胞机制的深入了解，一些新的潜在治疗靶点被发现，这些靶点能够诱导心肌重塑的消退。在这篇文章中，我们的注意力集中在抗凋亡和抗纤维化药物的可能使用上，以及心肌基因治疗特别是心肌再生治疗的发展所提供的迷人的前景。
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.
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DOI：
10.1073/pnas.85.2.339
发表时间：
1988-01-01
影响因子：
11.1
作者：
IZUMO, S;NADALGINARD, B;MAHDAVI, V
通讯作者：
MAHDAVI, V
影响因子：
20.1
作者：
Clark, JE;Naughton, P;Motterlini, R
通讯作者：
Motterlini, R
影响因子：
6
作者：
Jaski, Brian E.;Jessup, Mariell L.;Mancini, Donna M.;Cappola, Thomas P.;Pauly, Daniel F.;Greenberg, Barry;Borow, Kenneth;Dittrich, Howard;Zsebo, Krisztina M.;Hajjar, Roger J.
通讯作者：
Hajjar, Roger J.
影响因子：
3.6
作者：
Distefano G
通讯作者：
Distefano G
Anthracycline心肌病是通过心脏干细胞池的耗竭介导的，并通过恢复祖细胞功能而挽救。
影响因子：
37.8
作者：
De Angelis A;Piegari E;Cappetta D;Marino L;Filippelli A;Berrino L;Ferreira-Martins J;Zheng H;Hosoda T;Rota M;Urbanek K;Kajstura J;Leri A;Rossi F;Anversa P
通讯作者：
Anversa P