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是保护性的，但雄激素的作用尚未明确。雄激素可通过不同途径诱发或加重高血压和心肌肥厚。然而，雄激素的有益心血管作用也已被描述。除了它们对由“经典”雄激素受体（AR）介导的靶基因的转录活性的众所周知的作用之外，雄激素还在许多细胞类型（包括心肌细胞和内皮细胞）中发挥快速的非基因组作用。这些作用涉及细胞内钙的增加、激酶如ERK 1/2、Akt的活化、mTOR的磷酸化以及离子通道的调节。除了AR的基因组作用外，雄激素的快速作用可能是心肌肥大发生中性别差异的原因。关于负责受体和AR参与快速作用的结果不一致。不同组织中的介导蛋白可能不同。由于这些分子机制尚未得到很好的理解，潜在的治疗意义的快速雄激素的行动仍然没有探索。我们的团队将进一步分析在第一个资助期产生的新动物模型的表型，这些模型在心肌细胞和内皮细胞中改变了AR的表达，并使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和生理学和病理生理学功能。

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.