Project Details
Projekt
Cell-specific functions of bone morphogenetic proteins during vascular regeneration
Subject Area
Pharmacology
Cardiology, Angiology
Cardiology, Angiology
Term
from 2020 to 2024
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 439704927
Peripheral artery disease affects more than 200 million people worldwide. Many strategies of therapeutic revascularization have been proposed over the past years, including the administration of growth factors, diverse proteins with intrinsic proangiogenic activity, stem/progenitor cells, or pharmacological molecules. However, their success rates vary, and translation into routine clinic are still missing. Bone morphogenetic proteins (BMPs) are members of the transforming growth factor β superfamily and were originally identified by their ability to induce ectopic bone formation. Increasing evidence also suggest an essential role of BMPs in the vasculature, and various BMP isoforms, e.g. BMP2 and 4 have been shown to regulate growth and migration of endothelial cells. However, their mode of action during vascular regeneration seems to be cell-type dependent and in-depth evaluation of the pathways is still missing. In this grant application, the applicants aim to systematically investigate: 1) cell-type specific expression of BMP signaling pathway members, and especially BMP4-associated signaling pathways in two experimental mouse models of vascular remodeling (hindlimb ischemia and carotid artery wire injury) as well as specific BMP Smad responsive cell types using BRE:gfp transgenic mice, 2) characterization of phenotypic changes during vascular remodeling upon specific deletion of BMP4 in vascular cell-types (ECs and vSMCs) and “cell-type X”( cell-type with the highest expression level of BMP4 ligand which will be identified in specific aim 1), and 3) the functional consequences of cell-type specific interference of the BMP signaling pathway and the effect on heterocellular cell communication. Overall, our goal is to understand cell-type specific functions of BMP signaling in-depth, and eventually translate these findings from bench to clinical applications.
DFG Programme
Research Grants
