The fibrosis-cell death axis in heart failure.
The fibrosis-cell death axis in heart failure.
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DOI：
10.1007/s10741-016-9536-9
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发表时间：
2016-03
影响因子：
4.6
通讯作者：
Silljé HH
中科院分区：
文献类型：
--
作者：
Piek A;de Boer RA;Silljé HH
心脏应激可引起心脏形态、结构和功能的改变，称为心脏重塑。由于病理性原因（如高血压或瓣膜功能不全）引起的心肌梗死或持续超负荷可能导致进行性重构，最终导致心力衰竭（HF）。尽管病理性和生理性（运动、妊娠）负荷都刺激心肌细胞生长（肥大），但只有病理性重塑的特征是细胞外基质蛋白沉积增加，称为纤维化，心肌细胞因坏死、凋亡和/或吞噬而损失。心衰与年龄密切相关，心肌细胞损失和纤维化是心脏老化的典型迹象。纤维化导致心脏硬化、传导问题和氧扩散减少，并与心室功能减退和心律失常有关。因此，纤维化心脏中心肌细胞的负荷进一步增加，而生理环境变得不那么有利。这导致额外的心肌细胞死亡，并由纤维化物质取代失去的心肌细胞，形成心功能进一步下降的恶性循环。打破这个纤维化-细胞死亡轴可以阻止进一步的病理性和年龄相关的心脏退化，并可能逆转重构。在这篇综述中，我们将描述心脏纤维化、心肌细胞肥大和细胞死亡之间的相互作用，并讨论解决进行性心脏重塑和心衰的潜在策略。
Cardiac stress can induce morphological, structural and functional changes of the heart, referred to as cardiac remodeling. Myocardial infarction or sustained overload as a result of pathological causes such as hypertension or valve insufficiency may result in progressive remodeling and finally lead to heart failure (HF). Whereas pathological and physiological (exercise, pregnancy) overload both stimulate cardiomyocyte growth (hypertrophy), only pathological remodeling is characterized by increased deposition of extracellular matrix proteins, termed fibrosis, and loss of cardiomyocytes by necrosis, apoptosis and/or phagocytosis. HF is strongly associated with age, and cardiomyocyte loss and fibrosis are typical signs of the aging heart. Fibrosis results in stiffening of the heart, conductivity problems and reduced oxygen diffusion, and is associated with diminished ventricular function and arrhythmias. As a consequence, the workload of cardiomyocytes in the fibrotic heart is further augmented, whereas the physiological environment is becoming less favorable. This causes additional cardiomyocyte death and replacement of lost cardiomyocytes by fibrotic material, generating a vicious cycle of further decline of cardiac function. Breaking this fibrosis-cell death axis could halt further pathological and age-related cardiac regression and potentially reverse remodeling. In this review, we will describe the interaction between cardiac fibrosis, cardiomyocyte hypertrophy and cell death, and discuss potential strategies for tackling progressive cardiac remodeling and HF.