Regulation of atrial gap junction protein expression and function by noradrenalin, angiotensin and atrial fibrillation. Aspects of receptor crosstalk

去甲肾上腺素、血管紧张素和心房颤动对心房间隙连接蛋白表达和功能的调节。

• 批准号: 20517718
• 负责人: Professor Dr. Stefan Dhein
• 金额: --
• 依托单位: Klinik für Herzchirurgie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2006
• 资助国家: 德国
• 起止时间: 2005-12-31 至 2009-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/20517718?language=en
• 关键词: Regulation; atrial; gap; junction; protein

Atrial fibrillation (AF) is a common problem in cardiology and cardiac surgery. The success rate of treatment decreases with duration of AF due to remodelling involving (among other factors) altered expression of gap junction channels formed by the connexins (Cx) Cx40 and Cx43 and Cx-redistribution within the cell (from cell poles to the lateral side), thereby changing the tissues biophysical properties which may enable multiple wavelets and perpetuate AF being now fixed on a structural basis. Cx-expression is influenced by angiotensin via AT1, which is up-regulated in AF. Since noradrenalin is enhanced in many cardiac diseases (e.g. AF associated with hemodynamic relevant mitral valve disease), the role of ¿- or ß-adrenoceptor stimulation on cardiac Cx expression should be investigated in absence and presence of angiotensin in cultured rat cardiomyocytes, in comparison to human tissue samples. First experiments show that chronic ß- and (-adrenoceptor stimulation both can up-regulate Cx43. The signal transduction pathways should be investigated including a possible shift of the ß2-adrenoceptor from Gs to Gi (because of chronic ß-AR-stimulation) and the resulting changes in MAPKactivation. Since angiotensin-II can alter the expression of cardiac adrenoceptors via TGFß1 combined stimulation (catecholamines + angiotensin-II) should also be investigated.

心房颤动（AF）是心脏病学和心脏外科的常见问题。治疗的成功率随着AF的持续时间而降低，这是由于重塑涉及（除其他因素外）由连接蛋白（Cx）Cx40和Cx43形成的间隙连接通道的表达改变以及细胞内的Cx重新分布（从细胞极到侧面），从而改变组织的生物物理特性，这可能使多个小波成为可能，并使AF永久化，现在在结构基础上固定。Cx表达受血管紧张素通过AT 1的影响，AT 1在AF中上调。由于去甲肾上腺素在许多心脏疾病中增强（例如，与血流动力学相关的二尖瓣疾病相关的AF），因此应研究在培养的大鼠心肌细胞中存在和不存在血管紧张素的情况下，与人体组织样本相比，<$-或<$-肾上腺素受体刺激对心脏Cx表达的作用。第一个实验表明，慢性β-和β-肾上腺素受体刺激都可以上调Cx43。应研究信号转导途径，包括β 2-肾上腺素受体从Gs到Gi的可能转移（由于慢性β-AR刺激）和MAPK活化的结果变化。由于血管紧张素-II可通过TGF β 1改变心脏肾上腺素受体的表达，因此还应研究联合刺激（儿茶酚胺+血管紧张素-II）。