心脏β受体亚型与慢性心功能不全

Cardiac β-adrenoceptor subtypes and chronic heart failure

β-肾上腺素受体兴奋是心肌收缩力增强和心输出量增加的重要原因。但持续的β受体兴奋能够促进心脏的病理性改变,如心肌细胞肥大和细胞凋亡,这是慢性心功能不全的成因之一。心脏同时存在β1受体、β2受体和β3受体,分别激活不同的信号转导通路。β2受体的持续激活能使心肌通过Gi-磷酯酰肌醇3激酶-蛋白激酶B途径,防止心肌细胞的凋亡,而长期的β1受体激活能通过蛋白激酶A非依赖性的钙调素激酶Ⅱ途径,导致心肌细胞肥大和凋亡。这种受体亚型特异性的信号转导途径证实了应用兼有β2受体激动作用的β1受体阻断剂有助于慢性心功能不全的治疗。

β-adrenoceptor stimulation serves as the most powerful means to increase both the cardiac contractile and cardiac output in response to stress or exercise. However, sustained β-adrenoceptor stimulation promotes pathological cardiac remodeling such as myocyte hypertrophy and apoptosis, which contributes to heart failure. Coexisting cardiac β-adrenoceptor subtypes, mainly β1-, β2-and β3-adrenoceptors, activate different signaling cascades. As a result, sustained β2-adrenoceptor stimulation protects cardiomyocytes against apoptosis via a Gi- phosphatidylinositol 3-kinase-protein kinase B pathway, whereas chronic β1-adrenoceptor stimulation induces myocyte hypertrophy and apoptosis by protein kinase A-independent activation of calmodulin kinase Ⅱ signaling. The mechanisms mentioned above help us to understand that β blockers with β-adrenoeeptor activation is beneficial to chronic heart failure.