{alpha}1-Adrenergic receptor subtypes in nonfailing and failing human myocardium.
{alpha}1-Adrenergic receptor subtypes in nonfailing and failing human myocardium.
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DOI：
10.1161/circheartfailure.108.846212
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发表时间：
2009-11
期刊：
影响因子：
--
通讯作者：
Simpson PC
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文献类型：
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作者：
Jensen BC;Swigart PM;De Marco T;Hoopes C;Simpson PC
α 1-肾上腺素能受体（α1-AR）在心脏中发挥适应性作用并防止心力衰竭（HF）的发展。α1-AR的三种亚型α1A、α1B和α1D在小鼠心脏中具有不同的生理作用，但对人心脏中的α1-亚型知之甚少。在这里，我们测试的假设，α1A和α1B亚型存在于人类心肌，类似于小鼠，并没有下调心力衰竭。来自移植受体和未使用供体的心脏衰竭（n = 12;平均EF 24%）或非衰竭（n = 9;平均EF 59%），年龄（约44岁）和性别（约70%男性）相似。采用实时定量逆转录聚合酶链反应（RT-PCR）和放射性配基结合法检测了两个心室多个区域的α1-AR亚型。所有三种α1-AR亚型mRNA均存在，其中α1A mRNA含量最高（约占总α1-AR mRNA的65%）。然而，仅存在α1A和α1B结合，并且α1B最丰富（占总量的60%）。在衰竭的心脏中，与β1-AR相比，α1A和α1B结合没有下调。我们的数据首次表明，α1A和α1B亚型都存在于人类心肌中，但α1D结合不存在，并且α1亚型在HF中没有下调。由于人类心脏中的α1亚型与小鼠相似，其中α1亚型的适应性和保护作用最令人信服，因此使用靶向α1A和/或α1B的药物治疗HF可能是可行的。
Alpha-1-adrenergic receptors (α1-ARs) play adaptive roles in the heart and protect against the development of heart failure (HF). The three α1-AR subtypes,α1A, α1B, and α1D, have distinct physiological roles in mouse heart, but very little is known about α1-subtypes in human heart. Here we test the hypothesis that the α1A and α1B subtypes are present in human myocardium, similar to the mouse, and are not down-regulated in heart failure. Hearts from transplant recipients and unused donors were failing (n = 12; mean EF 24%) or non-failing (n = 9; mean EF 59%), and similar in age (~44 years) and sex (~70% male). We measured the α1-AR subtypes in multiple regions of both ventricles by quantitative real-time reverse transcription PCR and radioligand binding. All three α1-AR subtype mRNAs were present, and α1A mRNA was most abundant (~65% of total α1-AR mRNA). However, only α1A and α1B binding were present, and the α1B was most abundant (60% of total). In failing hearts, α1A and α1B binding were not down-regulated, in contrast with β1-ARs. Our data show for the first time that the α1A and α1B subtypes are both present in human myocardium, but α1D binding is not, and that the α1-subtypes are not down-regulated in HF. Since α1-subtypes in the human heart are similar to mouse, where adaptive and protective effects of α1-subtypes are most convincing, it might become feasible to treat HF with a drug targeting the α1A and/or α1B.