Androgens in cardiac hypertrophy

雄激素与心脏肥大

• 批准号: 79521777
• 负责人: Professor Dr. Michael Bader
• 金额: --
• 依托单位: Forschungsgruppe Molekularbiologie von Hormonen im Herz-Kreislaufssystem
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2008
• 资助国家: 德国
• 起止时间: 2007-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/79521777?language=en
• 关键词: Androgens; cardiac; hypertrophy

In hypertensive cardiovascular diseases, estrogens and androgens have important pathophysiological effects. While estrogens seem to be mainly protective, the role of androgens is not yet well-defined. Androgens may induce or worsen hypertension and cardiac hypertrophy by different pathways. However, beneficial cardiovascular effects of androgens have also been described. Besides their well-known actions on the transcriptional activity of target genes mediated by the “classical” androgen receptor (AR), androgens also exert rapid, non-genomic effects in numerous cell types including cardiomyocytes and endothelial cells. These effects involve increases in intracellular calcium, activation of kinases such as ERK1/2, Akt, phosphorylation of mTOR, as well as the modulation of ion channels. Besides the genomic actions by the AR, the rapid effects of androgens may be a reason for sex differences in the development of myocardial hypertrophy. Results concerning the responsible receptors and the involvement of AR in the rapid actions are inconsistent. The mediating proteins are possibly different in different tissues. Since these molecular mechanisms are not yet well understood, potential therapeutic implications of the rapid androgen actions remained unexplored. Our group will further phenotypically analyse the new animal models generated in the first funding period with altered expression of AR in cardiomyocytes and endothelial cells and use them as well as suitable cell culture models to clarify the molecular mechanisms and the physiological and pathophysiological functions of rapid androgen signalling in the heart.

在高血压心血管疾病中，雌激素和雄激素具有重要的病理生理作用，虽然雌激素似乎主要具有保护作用，但雄激素的作用尚未明确，雄激素可能通过不同途径诱发或加重高血压和心脏肥大。雄激素除了对“经典”雄激素受体（AR）介导的靶基因转录活性具有众所周知的作用外，还对细胞产生快速的非基因组效应。这些效应涉及细胞内钙的增加、ERK1/2、Akt 等激酶的激活、mTOR 的磷酸化以及离子通道的调节。雄激素的快速作用可能是心肌肥大发展中性别差异的一个原因。有关负责受体和 AR 参与快速作用的结果不一致。由于这些分子机制尚未得到很好的了解，因此我们的小组将进一步对第一期资助期间产生的心肌细胞和内皮细胞中表达 AR 的新动物模型进行表型分析。并利用它们以及合适的细胞培养模型来阐明心脏中快速雄激素信号传导的分子机制以及生理和病理生理功能。

项目成果

Cardiomyocyte-derived CXCL12 is not involved in cardiogenesis but plays a crucial role in myocardial infarction

• DOI: 10.1007/s00109-016-1432-1
• 发表时间: 2016-09-01
• 期刊: JOURNAL OF MOLECULAR MEDICINE-JMM
• 影响因子: 4.7
• 作者: Muehlstedt, Silke;Ghadge, Santhosh K.;Bader, Michael
• 通讯作者: Bader, Michael

Effects of ACE2 deficiency on physical performance and physiological adaptations of cardiac and skeletal muscle to exercise

• DOI: 10.1038/hr.2016.28
• 发表时间: 2016-07-01
• 期刊: HYPERTENSION RESEARCH
• 影响因子: 5.4
• 作者: Motta-Santos, Daisy;Souza dos Santos, Robson Augusto;Bader, Michael
• 通讯作者: Bader, Michael

Functional Cross-Talk Between Aldosterone and Angiotensin-(1-7) in Ventricular Myocytes

• DOI: 10.1161/hypertensionaha.111.199539
• 发表时间: 2013-02
• 期刊: Hypertension
• 影响因子: 8.3
• 作者: Pedro W. Machado de Almeida;Ricardo de Freitas Lima;Enéas Ricardo de Morais Gomes;Cibele Rocha Resende;D. Roman-Campos;A. N. Gondim;Mariana Gavioli;Aline Lara;Amanda Parreira;Sasha Luísa de Azevedo Nunes;Márcia N M Alves;S. L. Santos;N. Alenina;M. Bader;R. Resende;J. dos Santos Cruz;R. A. Souza dos Santos;S. Guatimosim

Angiotensin-(1-7) receptor Mas is an essential modulator of extracellular matrix protein expression in the heart

• DOI: 10.1016/j.regpep.2012.01.001
• 发表时间: 2012-04-10
• 期刊: REGULATORY PEPTIDES
• 作者: Gava, Elisandra;de Castro, Carlos Henrique;Kitten, Gregory T.
• 通讯作者: Kitten, Gregory T.