Research progress on the role of β-adrenergic receptors in cardiac remodeling after infarction
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摘要: 心肌梗死后心脏重构涉及多种信号传导,与心力衰竭、心律失常密切相关。β肾上腺素能受体(β-AR)参与凋亡、炎症、纤维化、心肌肥大等病理过程,在梗死后心脏重构中发挥关键的调节作用。3种β-AR在梗死后重构中介导了不同的信号调节过程,交感神经持续过度刺激通过β1-AR促进不良重构,而β2-AR和β3-AR则发挥保护作用。深入了解β-AR信号传导途径将有助于开发新的药物来逆转不良重构。近年β2-AR和β3-AR的独特信号偶联以及对心脏重构产生的影响引起了广泛关注并且有望成为新的治疗靶点。实验和临床研究表明,β受体阻滞剂具有逆转心脏重构的作用。但是,不同的阻滞剂显示出不同程度的治疗效果,探索其潜在机制可能有助于开发更有效的药物。在动物模型和体外实验中,β2-AR和β3-AR激动剂均表现出抗肥大、抗氧化、抗纤维化作用,然而,这种有潜力的治疗干预在心脏重构中的作用须通过临床试验来证明。本文主要对β-AR调节梗死后心脏重构的机制,以及药物作用的潜在机制进行综述。Abstract: Cardiac remodeling after myocardial infarction involves a variety of signal transduction, which is closely related to heart failure and arrhythmia. β-adrenergic receptor(β-AR)is involved in apoptosis, inflammation, fibrosis, myocardial hypertrophy, and other pathological processes, and plays a key regulatory role in cardiac remodeling after myocardial infarction. Three kinds of β-AR mediate different signal regulation processes in post-infarction remodeling. Persistent overstimulation of the sympathetic nerve promotes adverse remodeling through β1-AR, while β2-AR and β3-AR play a protective role. In-depth understanding of β-AR signal transduction pathway will help to find a better way to reverse adverse remodeling. In recent years, the unique signal coupling of β2-AR and β3-AR and their effects on cardiac remodeling have attracted wide attention and are expected to become new therapeutic targets. Experimental and clinical studies have shown that β-blockers can reverse cardiac remodeling. However, different blockers show different degrees of therapeutic effects, and exploring their potential mechanism may help to develop more effective drugs. In animal models and in vitro experiments, β2-AR and β3-AR agonists showed anti-hypertrophy, anti-oxidation and anti-fibrosis effects. However, the role of this potential therapeutic intervention in cardiac remodeling must be proved by clinical trials. This article mainly reviews the mechanism of β-AR regulating cardiac remodeling after infarction and the potential mechanism of drug action.
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Key words:
- cardiac remodeling /
- myocardial infarction /
- β-adrenergic receptor /
- signal transduction /
- β-blockers
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