Project Details
Projekt
Extracellular ATP and purinergic receptors in atherosclerosis
Subject Area
Cardiology, Angiology
Term
from 2017 to 2023
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 326336632
Atherosclerosis and its sequelae such as myocardial infarction or stroke account for the highest morbidity and mortality worldwide. Vast experimental research and clinical science led to the appreciation of atherosclerosis as a chronic inflammatory, complex immunologic disease triggered by various external stimuli. Extracellular nucleotides such as ATP and their signaling via puringergic receptors could be a crucial factor in vascular inflammation and atherosclerosis: when cells are damaged or activated by inflammation, they release ATP into the extracellular space. There it binds to diverse purinergic receptors (P2X1-7, P2Y1-14) and acts as a pro-inflammatory warning signal. The aim of the proposed project is the comprehensive descriptive and functional analysis of extracellular ATP and its main receptors P2Y2 and P2X7 in the context of atherosclerosis in mice and man. Specifically, the following questions should be addressed: 1) What is the role of extracellular ATP and its receptors P2Y2 and P2X7 in early and late atherosclerosis? 2) How does extracellular ATP affect the vascular leukocyte recruitment? 3) Which cell types mediate vascular inflammation and atherosclerosis through P2Y2 and P2X7? 4) Which molecular mechanisms are behind the effects of extracellular ATP and its receptors P2Y2 and P2X7? 5) Does the expression of P2Y2 and P2X7 clinically associate with atherosclerosis and if so also with histologic criteria of plaque instability? Thus, we will elucidate key mechanisms of atherogenesis laying the foundation for novel futureanti-atherogenic therapies. Modulation of inflammatory signal pathways such as proposed here represents a potentially fruitful strategy in the combat of atherosclerosis.
DFG Programme
Research Grants
International Connection
Austria
