Project Details
Projekt
Macrophage proliferation, the engine of plaque progression
Applicant
Professor Dr. Ingo Hilgendorf
Subject Area
Cardiology, Angiology
Term
from 2014 to 2022
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 265188911
Macrophages are the most abundant cell type in atherosclerotic lesions. They ingest lipoproteins and produce inflammatory mediators and metalloproteinases that stimulate plaque growth and destabilization. This leads to angina pectoris and ultimately myocardial infarction after plaque rupture and coronary artery occlusion. Macrophages play a key role in the pathogenesis of atherosclerosis as evidenced by experimental studies in which monocyte depletion and inhibition of monocyte recruitment, the progenitor cells of lesional macrophages, reduced plaque formation. This established the prevailing concept that plaque growth and lesional macrophage accumulation depend on continuous monocyte recruitment and differentiation. The applicant challenged, however, this paradigm in a recent study from his postdoctoral fellowship in Boston. It shows that with disease progression plaque macrophage accumulation becomes increasingly and directly dependent on local macrophage proliferation rather then monocyte recruitment. This novel finding raises many interesting and important questions regarding plaque progression. Do all lesional macrophages proliferate equally? What is the particular contribution of proliferating macrophages to plaque inflammation? What are the factors that control lesional macrophage proliferation? Will direct or indirect inhibition of macrophage proliferation slow or even revert plaque development? What is the role of macrophage proliferation in other cardiovascular diseases? The following research proposal integrates mouse models and human sample analyses to address these questions. Uncovering the pathomechanisms of macrophage proliferation in cardiovascular disease is crucial for developing much needed novel therapeutic strategies for the number one cause of death in the world.
DFG Programme
Independent Junior Research Groups
