Understanding the involvement of mitochondrial inner membrane hyperpolarization in the development of myointimal hyperplasia

• Applicant: Professor Dr. Tobias Deuse
• Subject Area: Cardiac and Vascular Surgery
• Term: from 2015 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 284075022

Cardiovascular disease is the predominant cause of human morbidity and mortality in developed countries. Thus, extraordinary effort has been devoted to determine the molecular and pathophysiological characteristics of the diseased vasculature with the goal of developing novel diagnostic and therapeutic strategies to treat associated diseases (such as coronary artery disease or peripheral artery disease). Vessel injury triggers proliferative activity in vascular smooth muscle cells (SMCs) and concurrently suppresses their ability to undergo apoptosis. This temporary imbalance between SMC amplification and death leads to a largely positive net increase in cellularity, leading to myointimal hyperplasia. Activation of pyruvate dehydrogenase (PDH) via inhibition of its endogenous inhibitor PDK2, prevents the induction of apoptosis resistance in SMCs, maintains the homeostatic growth balance, and prevents vessel narrowing. We now aim to reveal the mechanism of this very effective and novel treatment and to screen for alternative drug candidates for translational use.

• DFG Programme: Research Grants