Angiotensin converting enzyme (ACE): regulation and dysregulation

血管紧张素转换酶 (ACE)：调节和失调

• 批准号: 234383115
• 负责人: Professorin Dr. Ingrid Fleming, Ph.D., since 3/2016
• 金额: --
• 依托单位: HSD Hochschule Döpfer
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2019-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/234383115?language=en
• 关键词: Angiotensin; converting; enzyme; ACE; regulation

The angiotensin converting enzyme (ACE) is a key part of the renin angiotensin system (RAS) and has been allocated a central role in cardiovascular disease development. Surprisingly, relatively little is known about the molecular event that regulate ACE expression or the full spectrum of consequences of increased expression. For example, recent findings demonstrated that ACE is not simply part of the pressor, pro-inflammatory arm of the RAS and may regulate new onset diabetes. This project will assess the molecular mechanisms regulating ACE levels in response to stimuli involved in the development of metabolic and inflammatory diseases (e.g. adipo-/cytokines), clarify the role of the metabolite-sensing kinase AMPK and the influence of an epigenetic control (histone modifications, miRNA). The impact of ACE expression on angiogenic, inflammatory and adipogenic processes will be assessed in vitro as well as on angiogenic processes also in vivo (e.g. on stem cell mobilization/neovascularization). The use of ACE inhibitors and mice expressing a signaling dead (S1270A) ACE mutant will help to clarify the role of ACE activity and/or the ACE signaling cascade. A re-evaluation of the consequences of cellular and tissue ACE expression may well serve as the basis for novel therapeutic strategies for the treatment of metabolic disorders that are linked to inflammatory processes, i.e. for the treatment of metabolic syndrome and type 2 diabetes.

血管紧张素转换酶（ACE）是肾素血管紧张素系统（RAS）的重要组成部分，在心血管疾病的发生发展中起着重要作用。令人惊讶的是，相对知之甚少的分子事件，调节ACE的表达或增加的表达的全部频谱的后果。例如，最近的研究结果表明，ACE不仅仅是RAS的升压、促炎臂的一部分，还可能调节新发糖尿病。该项目将评估调节ACE水平的分子机制，以响应参与代谢和炎症疾病发展的刺激（例如脂肪/细胞因子），阐明代谢物敏感激酶AMPK的作用和表观遗传控制（组蛋白修饰，miRNA）的影响。将在体外评估ACE表达对血管生成、炎症和脂肪形成过程的影响，以及在体内评估ACE表达对血管生成过程的影响（例如，对干细胞动员/新血管形成）。使用ACE抑制剂和表达信号死亡（S1270A）ACE突变体的小鼠将有助于阐明ACE活性和/或ACE信号级联的作用。对细胞和组织ACE表达的后果的重新评估可以很好地作为用于治疗与炎症过程相关的代谢紊乱的新治疗策略的基础，即用于治疗代谢综合征和2型糖尿病。

项目成果

Role of the angiotensin-converting enzyme in the G-CSF-induced mobilization of progenitor cells

• DOI: 10.1007/s00395-018-0677-y
• 发表时间: 2018-03
• 期刊: Basic Research in Cardiology
• 影响因子: 9.5
• 作者: K. Kohlstedt;Caroline Trouvain;Timo Frömel;Thomas Mudersbach;R. Henschler;I. Fleming

Cytochrome P4502S1: a novel monocyte/macrophage fatty acid epoxygenase in human atherosclerotic plaques

• DOI: 10.1007/s00395-012-0319-8
• 发表时间: 2013-01-01
• 期刊: BASIC RESEARCH IN CARDIOLOGY
• 影响因子: 9.5
• 作者: Froemel, Timo;Kohlstedt, Karin;Fleming, Ingrid
• 通讯作者: Fleming, Ingrid