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Updated: Apr 19, 2026
Quantification of Endothelial Fatty Acid Uptake using Fluorescent Fatty Acid Analogs
Published on: August 15, 2025
Meox2/Tcf15 heterodimers program the heart capillary endothelium for cardiac fatty acid uptake
Giulia Coppiello1, Maria Collantes1, María Salomé Sirerol-Piquer1
1From Department of Cardiovascular Sciences, Center for Molecular and Vascular Biology (G.C., I.V., X.L.A., A.L.), Department of Cardiovascular Sciences, Cardiology Unit (S.V., M.S., S.J.), Laboratory of Angiogenesis & Neurovascular link, Vesalius Research Center, VIB/Department of Oncology (S.S., P.C.), and Department of Cardiovascular Sciences, Experimental Cardiac Surgery Unit (P.H.), KULeuven, Belgium; Department of Nuclear Medicine, Clínica Universidad de Navarra/MicroPET Research Unit CIMA-CUN (M.C., I.P.), and Hematology and Cell Therapy Area, Clínica Universidad de Navarra and Division of Oncology, Center for Applied Medical Research (F.P., X.L.A), University of Navarra, Pamplona, Spain; Laboratory of Comparative Neurobiology, Instituto Cavanilles, University of Valencia, CIBERNED, Spain (M.S.S.-P., J.M.G.-V.); and Departments of Abdominal Surgery (B.T.) and Neurosurgery (J.v.L., J.G.), University Hospitals Leuven/KULeuven, Belgium.
Background:
Microvascular endothelium in different organs is specialized to fulfill the particular needs of parenchymal cells. However, specific information about heart capillary endothelial cells (ECs) is lacking.
Methods And Results:
Using microarray profiling on freshly isolated ECs from heart, brain, and liver, we revealed a genetic signature for microvascular heart ECs and identified Meox2/Tcf15 heterodimers as novel transcriptional determinants. This signature was largely shared with skeletal muscle and adipose tissue endothelium and was enriched in genes encoding fatty acid (FA) transport-related proteins. Using gain- and loss-of-function approaches, we showed that Meox2/Tcf15 mediate FA uptake in heart ECs, in part, by driving endothelial CD36 and lipoprotein lipase expression and facilitate FA transport across heart ECs. Combined Meox2 and Tcf15 haplodeficiency impaired FA uptake in heart ECs and reduced FA transfer to cardiomyocytes. In the long term, this combined haplodeficiency resulted in impaired cardiac contractility.
Conclusions:
Our findings highlight a regulatory role for ECs in FA transfer to the heart parenchyma and unveil 2 of its intrinsic regulators. Our insights could be used to develop new strategies based on endothelial Meox2/Tcf15 targeting to modulate FA transfer to the heart and remedy cardiac dysfunction resulting from altered energy substrate usage.
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