title: Expression of vascular endothelial growth factor (VEGF)-B and its receptor (VEGFR1) in murine heart, lung and kidney.
abstract: Metabolic diseases, such as obesity and diabetes, are a serious burden for the health system. Vascular endothelial growth factor (VEGF)-B has been shown to regulate tissue uptake and accumulation of fatty acids and is thus involved in these metabolic diseases. However, the cell-type-specific expression pattern of Vegfb and its receptor (VEGFR1, gene Flt1) remains unclear. We explore the expression of Vegfb and Flt1 in the murine heart, lung and kidney by utilizing β-galactosidase knock-in mouse models and combining the analysis of reporter gene expression and immunofluorescence microscopy. Furthermore, Flt1 heterozygous mice were analyzed with regard to muscular fatty acid accumulation and peripheral insulin sensitivity. Throughout the heart, Vegfb expression was found in cardiomyocytes with a postnatal ventricular shift corresponding to known changes in energy requirements. Vegfb expression was also found in the pulmonary myocardium of the lung and in renal epithelial cells of the thick ascending limb of Henle's loop, the connecting tubule and the collecting duct. In all analyzed organs, VEGFR1 expression was restricted to endothelial cells. We also show that reduced expression of VEGFR1 resulted in decreased cardiac fatty acid accumulation and increased peripheral insulin sensitivity, possibly as a result of attenuated VEGF-B/VEGFR1 signaling. Our data therefore support a tightly controlled, paracrine signaling mechanism of VEGF-B to VEGFR1. The identified cell-specific expression pattern of Vegfb and Flt1 might form the basis for the development of cell-type-targeted research models and contributes to the understanding of the physiological and pathological role of VEGF-B/VEGFR1 signaling.
authors.affiliation: Department of Medical Biochemistry and Biophysics, Division of Vascular Biology, Karolinska Institutet, Scheeles Väg 2, A3:P4, 17177, Stockholm, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Muhl
authors.affiliation: Department of Medical Biochemistry and Biophysics, Division of Vascular Biology, Karolinska Institutet, Scheeles Väg 2, A3:P4, 17177, Stockholm, Sweden.
authors.forename: Christine
authors.initials: C
authors.lastname: Moessinger
authors.affiliation: Department of Medical Biochemistry and Biophysics, Division of Vascular Biology, Karolinska Institutet, Scheeles Väg 2, A3:P4, 17177, Stockholm, Sweden.
authors.forename: Milena Z
authors.initials: MZ
authors.lastname: Adzemovic
authors.affiliation: Department Biotechnology and Molecular Medicine, A.I.V. Institute for Molecular Science, University of Eastern Finland, Kuopio, Finland.
authors.forename: Marike H
authors.initials: MH
authors.lastname: Dijkstra
authors.affiliation: Department of Medical Biochemistry and Biophysics, Division of Vascular Biology, Karolinska Institutet, Scheeles Väg 2, A3:P4, 17177, Stockholm, Sweden.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Nilsson
authors.affiliation: Department of Medical Biochemistry and Biophysics, Division of Vascular Biology, Karolinska Institutet, Scheeles Väg 2, A3:P4, 17177, Stockholm, Sweden.
authors.forename: Manuel
authors.initials: M
authors.lastname: Zeitelhofer
authors.affiliation: Department of Medical Biochemistry and Biophysics, Division of Vascular Biology, Karolinska Institutet, Scheeles Väg 2, A3:P4, 17177, Stockholm, Sweden.|Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Carolina E
authors.initials: CE
authors.lastname: Hagberg
authors.affiliation: Department Biotechnology and Molecular Medicine, A.I.V. Institute for Molecular Science, University of Eastern Finland, Kuopio, Finland.
authors.forename: Jenni
authors.initials: J
authors.lastname: Huusko
authors.affiliation: Department of Medical Biochemistry and Biophysics, Division of Vascular Biology, Karolinska Institutet, Scheeles Väg 2, A3:P4, 17177, Stockholm, Sweden.
authors.forename: Annelie
authors.initials: A
authors.lastname: Falkevall
authors.affiliation: Department Biotechnology and Molecular Medicine, A.I.V. Institute for Molecular Science, University of Eastern Finland, Kuopio, Finland.
authors.forename: Seppo
authors.initials: S
authors.lastname: Ylä-Herttuala
authors.affiliation: Department of Medical Biochemistry and Biophysics, Division of Vascular Biology, Karolinska Institutet, Scheeles Väg 2, A3:P4, 17177, Stockholm, Sweden. Ulf.PE.Eriksson@ki.se.
authors.forename: Ulf
authors.initials: U
authors.lastname: Eriksson
mesh_terms: D000818:Animals; D004847:Epithelial Cells / Q000378:metabolism; D006321:Heart / Q000502:physiology*; D006579:Heterozygote; D007668:Kidney / Q000166:cytology / Q000378:metabolism*; D008168:Lung / Q000098:blood supply / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D010641:Phenotype; D011667:Pulmonary Veins / Q000166:cytology / Q000378:metabolism; D042561:Vascular Endothelial Growth Factor B / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism*
chemical_list: D042561:Vascular Endothelial Growth Factor B; D040281:Vascular Endothelial Growth Factor Receptor-1
keywords: Endothelial cells; Gene expression pattern; Insulin sensitivity; VEGF-B; VEGFR1