摘要
在运动或应激状况下,β肾上腺素受体(βAR)的激活可有力地增加心输出量。然而,心衰时持续的βAR激活可导致心肌肥大、心肌细胞凋亡等病理性心肌重塑过程。目前认为,心肌细胞表面存在结构、效应特异的三种βAR亚型:β1、β2及β3AR。β1AR可激活经典的Gs-AC-cAMP-PKA信号通路;β2AR同时激活Gs-AC-cAMP-PKA及Giα-Giβγ-PI3K-Akt信号通路;而β3AR则通过Gi-eNOS-NO-cGMP介导负性变力效应。目前研究表明:心衰时长期的β1AR激活可通过Gs-Ca2+-CaMKⅡ通路导致心肌肥大、心肌细胞凋亡等病理性心肌重塑过程;而持续的β2AR刺激则通过Giα-Giβγ-PI3K-Akt通路产生抗心肌肥大、心肌细胞凋亡效应。对心衰时上述βAR亚型的信号转导、效应的深入认识不仅对βAR阻滞剂治疗慢性心衰提供了分子和细胞机制的依据,而且为我们带来了一些治疗慢性心衰的新思路。
β-Adrenergic receptors stimulation serves as the most powerful means to increase cardiac output in response to stress or exercise.However,sustained β-adrenergic receptors stimulation promotes pathological cardiac remodeling such as myocyte hypertrophy and apoptosis,thus contributing to heart failure.Coexisting cardiac β-adrenergic receptor subtypes,β1,β2 and β3AR,activate different signaling cascades：β1AR-Gs-AC-cAMP-PKA;β2AR coupling to Gs-AC-cAMP-PKA and Giα-Giβγ-PI3K-Akt;β3AR mediate negative intropic effect by Gi-eNOS-NO-cGMP.As a result,chronic β1AR stimulation induces myocyte hypertrophy and apop-tosis by Gs-Ca2＋ -CaMKⅡ signaling,whereas sustained β2AR stimulation protects cardiomyocytes against apoptosis via Giα-Giβγ-PI3K-Akt pathway.These new insights regarding βAR subtypes stimulation not only provide clues as to cellular and molecular mechanisms underlying the beneficial effects of βAR blockers in patients with chronic heart failure,but slao delineate some potential novel therapies for the treatment of chronic heart failure.
出处
《现代生物医学进展》
CAS
2010年第7期1374-1377,1397,共5页
Progress in Modern Biomedicine
基金
国家自然科学基金资助项目(30572073)
江苏省医学135工程重点人才研究基金(RC2007024)
关键词
β肾上腺素受体亚型
信号转导
心衰
β-adrenergic receptor subtypes
Signal transduction
Chronic heart failure.
