CRIM1 is necessary for coronary vascular endothelial cell development and homeostasis.
Endothelial cells form a critical component of the coronary vasculature, yet the factors regulating their development remain poorly defined. Here we reveal a novel role for the transmembrane protein CRIM1 in mediating cardiac endothelial cell development. In the absence of Crim1 in vivo, the coronary vasculature is malformed, the number of endothelial cells reduced, and the canonical BMP pathway dysregulated. Moreover, we reveal that CRIM1 can bind IGFs, and regulate IGF signalling within endothelial cells. Finally, loss of CRIM1 from human cardiac endothelial cells results in misregulation of endothelial genes, predicted by pathway analysis to be involved in an increased inflammatory response and cytolysis, reminiscent of endothelial cell dysfunction in cardiovascular disease pathogenesis. Collectively, these findings implicate CRIM1 in endothelial cell development and homeostasis in the coronary vasculature.
School of Biomedical Sciences, The University of Queensland, Brisbane, 4072, Australia.
Swati
S
Iyer
School of Biomedical Sciences, The University of Queensland, Brisbane, 4072, Australia.
Yash
Y
Chhabra
School of Biomedical Sciences, The University of Queensland, Brisbane, 4072, Australia.
Tracey J
TJ
Harvey
School of Biomedical Sciences, The University of Queensland, Brisbane, 4072, Australia.
Richard
R
Wang
School of Biomedical Sciences, The University of Queensland, Brisbane, 4072, Australia.
Han Sheng
HS
Chiu
School of Biomedical Sciences, The University of Queensland, Brisbane, 4072, Australia.
A G
AG
Smith
School of Biomedical Sciences, The University of Queensland, Brisbane, 4072, Australia.
Walter G
WG
Thomas
School of Biomedical Sciences, The University of Queensland, Brisbane, 4072, Australia. d.pennisi@uq.edu.au.
David J
DJ
Pennisi
School of Biomedical Sciences, The University of Queensland, Brisbane, 4072, Australia. m.piper@uq.edu.au.|Queensland Brain Institute, The University of Queensland, Brisbane, 4072, Australia. m.piper@uq.edu.au.
Michael
http://orcid.org/0000-0002-6759-2560
M
Piper
D000818:Animals; D052004:Bone Morphogenetic Protein Receptors / Q000235:genetics* / Q000378:metabolism*; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002470:Cell Survival / Q000235:genetics; D003331:Coronary Vessels / Q000166:cytology*; D042783:Endothelial Cells / Q000378:metabolism*; D006706:Homeostasis; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D015398:Signal Transduction
D019485:Bone Morphogenetic Proteins; C518411:Crim1 protein, mouse; D052004:Bone Morphogenetic Protein Receptors
Crim 1; Endothelial cells; Heart