iNOS- and NoxO1-based redox signaling in chronic obstructive pulmonary disease (COPD) associated PH – pathomechanisms and therapeutic exploitation (A07)

• Subject Area: Pneumology, Thoracic Surgery
• Term: since 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 268555672

We aim to investigate the mechanisms and consequences of the iNOS- and NADPH oxidase subunit NoxO1-dependent communication between lung cell types underlying COPD-PH. We ask: 1) What is the phenotype of iNOS-expressing macrophages that drive pulmonary vascular remodeling; can their removal reverse this process? 2) Does iNOS- and NoxO1-based redox signaling lead to COPD-PH via inflammation or does it directly stimulate pulmonary vascular remodeling, 3) Does protein nitration modulate the pro-inflammatory response in the alveolar epithelium and endothelium? Finally, we will evaluate the NoxO1-specific proteolysis targeting chimera system and newly developed iNOS-inhibition strategies as possible therapeutic approaches to reverse COPD-PH.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1213: Pulmonary Hypertension and Cor Pulmonale
• Applicant Institution: Justus-Liebig-Universität Gießen
• Project Heads: Marija Gredic, Ph.D.; Professor Dr. Norbert Weißmann