Neyses L, Pelzer T
Department of Cardiology, University of Würzburg, Germany.
Eur Heart J. 1995 Dec;16 Suppl N:8-11. doi: 10.1093/eurheartj/16.suppl_n.8.
Cardiac hypertrophy, one of the major risk factors in hypertension, is associated with a high incidence of congestive heart failure and sudden death. Despite efforts over the last 20 years, the underlying molecular mechanisms of cardiac hypertrophy are still poorly understood, thus making it difficult to develop new therapeutic strategies. A growing body of evidence suggests that cardiac hypertrophy results from mechanical stress that triggers paracrine and autocrine signal transduction pathways. Furthermore, whereas hypertrophy leads to isoform switches in some contractile proteins, increased protein synthesis is largely based on increased translational capacity. Cardiac growth under physiological as well as pathological conditions is regulated by several recently identified transcription factors. Among the factors that are capable of transmitting hypertrophic stimuli to the nucleus is the early growth response gene-1 (Egr-1). Whereas female gender is already an established cardioprotective factor in clinical trials, some very recent data indicate that oestrogens and the nuclear oestrogen receptor may directly modulate gene expression in the development of cardiac hypertrophy. Future pharmacological interventions could be directed towards modifying the nuclear signal transduction cascade involving multiple protein kinases and phosphatases.
心脏肥大是高血压的主要危险因素之一，与充血性心力衰竭和猝死的高发生率相关。尽管在过去20年中进行了诸多努力，但心脏肥大的潜在分子机制仍未得到充分了解，因此难以开发新的治疗策略。越来越多的证据表明，心脏肥大是由机械应力引发旁分泌和自分泌信号转导通路所致。此外，虽然肥大导致一些收缩蛋白的亚型转换，但蛋白质合成增加主要基于翻译能力的提高。生理和病理条件下的心脏生长受几种最近发现的转录因子调控。能够将肥大刺激传递至细胞核的因子之一是早期生长反应基因-1（Egr-1）。虽然女性性别在临床试验中已被确认为一种心脏保护因素，但一些最新数据表明，雌激素和核雌激素受体可能在心脏肥大的发展过程中直接调节基因表达。未来的药物干预可针对修饰涉及多种蛋白激酶和磷酸酶的核信号转导级联反应。
