Angiotensin converting enzyme (ACE): regulation and dysregulation

• Applicant: Professorin Ingrid Fleming, Ph.D., since 3/2016
• Subject Area: Cardiology, Angiology
• Term: from 2013 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 234383115

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.

• DFG Programme: Research Grants
• Ehemalige Antragstellerin: Dr. Karin Kohlstedt, until 3/2016