Impact of Aldosterone on the Failing Myocardium: Insights from Mitochondria and Adrenergic Receptors Signaling and Function.
Impact of Aldosterone on the Failing Myocardium: Insights from Mitochondria and Adrenergic Receptors Signaling and Function.
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醛固酮对心肌失败的影响：线粒体和肾上腺素能受体信号传导和功能的见解。
DOI：
10.3390/cells10061552
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发表时间：
2021-06-19
期刊：
影响因子：
6
通讯作者：
Solesio ME
中科院分区：
文献类型：
--
作者：
Guitart-Mampel M;Urquiza P;Borges JI;Lymperopoulos A;Solesio ME
矿化皮质激素醛固酮调节电解质和血容量稳态，但它也通过慢性人心肌梗死后（MI）心力衰竭（HF）中醛固酮的升高而对慢性心力衰竭的结构和功能产生不利调节。醛固酮通过激活矿物皮质激素受体（MR）（一种配体调节的转录因子），促进心脏炎症和纤维化，同时增加氧化应激，最终导致衰竭心肌的线粒体功能障碍。为了降低晚期心衰的发病率和死亡率，MR拮抗剂如螺内酯和依普利酮被使用。除了MR，醛固酮还可以结合和刺激其他受体，如质膜上的G蛋白偶联雌激素受体（GPER），进一步使其在心肌中的信号传导特性复杂化。鉴于肾上腺素能受体（ARs）——尤其是βARs——在心脏生理和病理中发挥的显著作用，醛固酮对衰竭心脏的部分影响是通过其对这些受体的信号传导和功能的影响来介导的。醛固酮可显著促进心脏AR信号的紊乱和AR功能的损害，这是慢性人类HF的关键基础。在细胞水平的哺乳动物模型中，HF的主要后果之一是线粒体功能障碍的存在。因此，预防线粒体功能障碍可能是这种情况下有效的药理学靶点。本文综述了目前在健康和衰竭心脏中醛固酮/AR串扰的实验证据，以及线粒体功能障碍对心衰的影响。最近的信号研究发现，通过非常规的信号分子，即G蛋白偶联受体激酶（GRKs）， MR和AR串扰通常终止心脏中AR的信号传导，也得到了强调。
The mineralocorticoid aldosterone regulates electrolyte and blood volume homeostasis, but it also adversely modulates the structure and function of the chronically failing heart, through its elevated production in chronic human post-myocardial infarction (MI) heart failure (HF). By activating the mineralocorticoid receptor (MR), a ligand-regulated transcription factor, aldosterone promotes inflammation and fibrosis of the heart, while increasing oxidative stress, ultimately induding mitochondrial dysfunction in the failing myocardium. To reduce morbidity and mortality in advanced stage HF, MR antagonist drugs, such as spironolactone and eplerenone, are used. In addition to the MR, aldosterone can bind and stimulate other receptors, such as the plasma membrane-residing G protein-coupled estrogen receptor (GPER), further complicating it signaling properties in the myocardium. Given the salient role that adrenergic receptor (ARs)—particularly βARs—play in cardiac physiology and pathology, unsurprisingly, that part of the impact of aldosterone on the failing heart is mediated by its effects on the signaling and function of these receptors. Aldosterone can significantly precipitate the well-documented derangement of cardiac AR signaling and impairment of AR function, critically underlying chronic human HF. One of the main consequences of HF in mammalian models at the cellular level is the presence of mitochondrial dysfunction. As such, preventing mitochondrial dysfunction could be a valid pharmacological target in this condition. This review summarizes the current experimental evidence for this aldosterone/AR crosstalk in both the healthy and failing heart, and the impact of mitochondrial dysfunction in HF. Recent findings from signaling studies focusing on MR and AR crosstalk via non-conventional signaling of molecules that normally terminate the signaling of ARs in the heart, i.e., the G protein-coupled receptor-kinases (GRKs), are also highlighted.
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β-arrestin-1 通过心脏和肾上腺依赖性神经激素机制对心肌梗死后心力衰竭产生负面影响。
DOI：
10.1161/hypertensionaha.113.02043
发表时间：
2014-02
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
--
作者：
Bathgate-Siryk A;Dabul S;Pandya K;Walklett K;Rengo G;Cannavo A;De Lucia C;Liccardo D;Gao E;Leosco D;Koch WJ;Lymperopoulos A
通讯作者：
Lymperopoulos A
影响因子：
41.5
作者：
Brown, Nancy J.
通讯作者：
Brown, Nancy J.
影响因子：
10.8
作者：
Churchill EN;Ferreira JC;Brum PC;Szweda LI;Mochly-Rosen D
通讯作者：
Mochly-Rosen D
影响因子：
5.8
作者：
Bollag, Wendy B.
通讯作者：
Bollag, Wendy B.
影响因子：
2.8
作者：
Bristow, MR
通讯作者：
Bristow, MR