Your browser doesn't support javascript.
loading
Quiescent Endothelial Cells Upregulate Fatty Acid ß-Oxidation for Vasculoprotection via Redox Homeostasis.
Kalucka, Joanna; Bierhansl, Laura; Conchinha, Nadine Vasconcelos; Missiaen, Rindert; Elia, Ilaria; Brüning, Ulrike; Scheinok, Samantha; Treps, Lucas; Cantelmo, Anna Rita; Dubois, Charlotte; de Zeeuw, Pauline; Goveia, Jermaine; Zecchin, Annalisa; Taverna, Federico; Morales-Rodriguez, Francisco; Brajic, Aleksandra; Conradi, Lena-Christin; Schoors, Sandra; Harjes, Ulrike; Vriens, Kim; Pilz, Gregor-Alexander; Chen, Rongyuan; Cubbon, Richard; Thienpont, Bernard; Cruys, Bert; Wong, Brian W; Ghesquière, Bart; Dewerchin, Mieke; De Bock, Katrien; Sagaert, Xavier; Jessberger, Sebastian; Jones, Elizabeth A V; Gallez, Bernard; Lambrechts, Diether; Mazzone, Massimiliano; Eelen, Guy; Li, Xuri; Fendt, Sarah-Maria; Carmeliet, Peter.
Afiliação
  • Kalucka J; Laboratory of Angiogenesis and Vascular Metabolism, VIB Center for Cancer Biology (CCB), VIB, 3000 Leuven, Belgium; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 51006, Guangdong, P.R. China; Laboratory of Angiogenesis and Vascular Metabolism,
  • Bierhansl L; Laboratory of Angiogenesis and Vascular Metabolism, VIB Center for Cancer Biology (CCB), VIB, 3000 Leuven, Belgium; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, 3000 Leuven, Belgium.
  • Conchinha NV; Laboratory of Angiogenesis and Vascular Metabolism, VIB Center for Cancer Biology (CCB), VIB, 3000 Leuven, Belgium; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, 3000 Leuven, Belgium.
  • Missiaen R; Laboratory of Angiogenesis and Vascular Metabolism, VIB Center for Cancer Biology (CCB), VIB, 3000 Leuven, Belgium; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, 3000 Leuven, Belgium.
  • Elia I; Laboratory of Cellular Metabolism and Metabolic Regulation, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, 3000 Leuven, Belgium; Laboratory of Cellular Metabolism and Metabolic Regulation, VIB Center for Cancer Biology, Center for Cancer Biology (CCB), VIB, 3000 Leuven, Belgium
  • Brüning U; Laboratory of Angiogenesis and Vascular Metabolism, VIB Center for Cancer Biology (CCB), VIB, 3000 Leuven, Belgium; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, 3000 Leuven, Belgium.
  • Scheinok S; Université Catholique de Louvain, Louvain Drug Research Institute, Biomedical Magnetic Resonance Research Group, 1200 Brussels, Belgium.
  • Treps L; Laboratory of Angiogenesis and Vascular Metabolism, VIB Center for Cancer Biology (CCB), VIB, 3000 Leuven, Belgium; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, 3000 Leuven, Belgium.
  • Cantelmo AR; Laboratory of Angiogenesis and Vascular Metabolism, VIB Center for Cancer Biology (CCB), VIB, 3000 Leuven, Belgium; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, 3000 Leuven, Belgium.
  • Dubois C; Laboratory of Angiogenesis and Vascular Metabolism, VIB Center for Cancer Biology (CCB), VIB, 3000 Leuven, Belgium; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, 3000 Leuven, Belgium.
  • de Zeeuw P; Laboratory of Angiogenesis and Vascular Metabolism, VIB Center for Cancer Biology (CCB), VIB, 3000 Leuven, Belgium; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, 3000 Leuven, Belgium.
  • Goveia J; Laboratory of Angiogenesis and Vascular Metabolism, VIB Center for Cancer Biology (CCB), VIB, 3000 Leuven, Belgium; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, 3000 Leuven, Belgium.
  • Zecchin A; Laboratory of Angiogenesis and Vascular Metabolism, VIB Center for Cancer Biology (CCB), VIB, 3000 Leuven, Belgium; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, 3000 Leuven, Belgium.
  • Taverna F; Laboratory of Angiogenesis and Vascular Metabolism, VIB Center for Cancer Biology (CCB), VIB, 3000 Leuven, Belgium; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, 3000 Leuven, Belgium.
  • Morales-Rodriguez F; Laboratory of Angiogenesis and Vascular Metabolism, VIB Center for Cancer Biology (CCB), VIB, 3000 Leuven, Belgium; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, 3000 Leuven, Belgium.
  • Brajic A; Laboratory of Angiogenesis and Vascular Metabolism, VIB Center for Cancer Biology (CCB), VIB, 3000 Leuven, Belgium; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, 3000 Leuven, Belgium.
  • Conradi LC; Laboratory of Angiogenesis and Vascular Metabolism, VIB Center for Cancer Biology (CCB), VIB, 3000 Leuven, Belgium; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, 3000 Leuven, Belgium.
  • Schoors S; Laboratory of Angiogenesis and Vascular Metabolism, VIB Center for Cancer Biology (CCB), VIB, 3000 Leuven, Belgium; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, 3000 Leuven, Belgium.
  • Harjes U; Laboratory of Angiogenesis and Vascular Metabolism, VIB Center for Cancer Biology (CCB), VIB, 3000 Leuven, Belgium; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, 3000 Leuven, Belgium.
  • Vriens K; Laboratory of Cellular Metabolism and Metabolic Regulation, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, 3000 Leuven, Belgium; Laboratory of Cellular Metabolism and Metabolic Regulation, VIB Center for Cancer Biology, Center for Cancer Biology (CCB), VIB, 3000 Leuven, Belgium
  • Pilz GA; Brain Research Institute, Faculty of Medicine and Science, University of Zurich, Zurich 8057, Switzerland.
  • Chen R; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 51006, Guangdong, P.R. China.
  • Cubbon R; Division of Cardiovascular and Diabetes Research, Multidisciplinary Cardiovascular Research Centre, University of Leeds, Leeds LS2 9JT, UK.
  • Thienpont B; Laboratory of Translational Genetics, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, 3000 Leuven, Belgium; Laboratory of Translational Genetics, VIB Center for Cancer Biology (CCB), VIB, 3000 Leuven, Belgium.
  • Cruys B; Laboratory of Angiogenesis and Vascular Metabolism, VIB Center for Cancer Biology (CCB), VIB, 3000 Leuven, Belgium; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, 3000 Leuven, Belgium.
  • Wong BW; Laboratory of Angiogenesis and Vascular Metabolism, VIB Center for Cancer Biology (CCB), VIB, 3000 Leuven, Belgium; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, 3000 Leuven, Belgium.
  • Ghesquière B; Metabolomics Expertise Center, VIB Center for Cancer Biology (CCB), VIB, 3000 Leuven, Belgium; Metabolomics Expertise Center, Department of Oncology, KU Leuven, 3000 Leuven, Belgium.
  • Dewerchin M; Laboratory of Angiogenesis and Vascular Metabolism, VIB Center for Cancer Biology (CCB), VIB, 3000 Leuven, Belgium; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, 3000 Leuven, Belgium.
  • De Bock K; Laboratory of Angiogenesis and Vascular Metabolism, VIB Center for Cancer Biology (CCB), VIB, 3000 Leuven, Belgium; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, 3000 Leuven, Belgium.
  • Sagaert X; Translational Cell & Tissue Research, Department of Imaging & Pathology, KU Leuven, 3000 Leuven, Belgium.
  • Jessberger S; Brain Research Institute, Faculty of Medicine and Science, University of Zurich, Zurich 8057, Switzerland.
  • Jones EAV; Department of Cardiovascular Sciences, KU Leuven, UZ Herestraat 49, Box 911, 3000 Leuven, Belgium; Centre for Molecular and Vascular Biology, KU Leuven, UZ Herestraat 49, Box 911, 3000 Leuven, Belgium.
  • Gallez B; Université Catholique de Louvain, Louvain Drug Research Institute, Biomedical Magnetic Resonance Research Group, 1200 Brussels, Belgium.
  • Lambrechts D; Laboratory of Translational Genetics, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, 3000 Leuven, Belgium; Laboratory of Translational Genetics, VIB Center for Cancer Biology (CCB), VIB, 3000 Leuven, Belgium.
  • Mazzone M; Laboratory of Tumor Inflammation and Angiogenesis, VIB Center for Cancer Biology (CCB), VIB, 3000 Leuven, Belgium; Laboratory of Tumor Inflammation and Angiogenesis, Department of Oncology, University of Leuven, 3000 Leuven, Belgium.
  • Eelen G; Laboratory of Angiogenesis and Vascular Metabolism, VIB Center for Cancer Biology (CCB), VIB, 3000 Leuven, Belgium; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, 3000 Leuven, Belgium.
  • Li X; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 51006, Guangdong, P.R. China. Electronic address: lixr6@mail.sysu.edu.cn.
  • Fendt SM; Laboratory of Cellular Metabolism and Metabolic Regulation, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, 3000 Leuven, Belgium; Laboratory of Cellular Metabolism and Metabolic Regulation, VIB Center for Cancer Biology, Center for Cancer Biology (CCB), VIB, 3000 Leuven, Belgium
  • Carmeliet P; Laboratory of Angiogenesis and Vascular Metabolism, VIB Center for Cancer Biology (CCB), VIB, 3000 Leuven, Belgium; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 51006, Guangdong, P.R. China; Laboratory of Angiogenesis and Vascular Metabolism,
Cell Metab ; 28(6): 881-894.e13, 2018 12 04.
Article em En | MEDLINE | ID: mdl-30146488
Little is known about the metabolism of quiescent endothelial cells (QECs). Nonetheless, when dysfunctional, QECs contribute to multiple diseases. Previously, we demonstrated that proliferating endothelial cells (PECs) use fatty acid ß-oxidation (FAO) for de novo dNTP synthesis. We report now that QECs are not hypometabolic, but upregulate FAO >3-fold higher than PECs, not to support biomass or energy production but to sustain the tricarboxylic acid cycle for redox homeostasis through NADPH regeneration. Hence, endothelial loss of FAO-controlling CPT1A in CPT1AΔEC mice promotes EC dysfunction (leukocyte infiltration, barrier disruption) by increasing endothelial oxidative stress, rendering CPT1AΔEC mice more susceptible to LPS and inflammatory bowel disease. Mechanistically, Notch1 orchestrates the use of FAO for redox balance in QECs. Supplementation of acetate (metabolized to acetyl-coenzyme A) restores endothelial quiescence and counters oxidative stress-mediated EC dysfunction in CPT1AΔEC mice, offering therapeutic opportunities. Thus, QECs use FAO for vasculoprotection against oxidative stress-prone exposure.
Assuntos
Palavras-chave

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carnitina O-Palmitoiltransferase / Metabolismo Energético / Receptor Notch1 / Ácidos Graxos / Células Endoteliais da Veia Umbilical Humana / NADP Limite: Animals / Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carnitina O-Palmitoiltransferase / Metabolismo Energético / Receptor Notch1 / Ácidos Graxos / Células Endoteliais da Veia Umbilical Humana / NADP Limite: Animals / Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article