ApoB-containing lipoproteins regulate angiogenesis by modulating expression of VEGF receptor 1.

Nature Medicine
Inbal Avraham-DavidiKarina Yaniv

Abstract

Despite the clear major contribution of hyperlipidemia to the prevalence of cardiovascular disease in the developed world, the direct effects of lipoproteins on endothelial cells have remained obscure and are under debate. Here we report a previously uncharacterized mechanism of vessel growth modulation by lipoprotein availability. Using a genetic screen for vascular defects in zebrafish, we initially identified a mutation, stalactite (stl), in the gene encoding microsomal triglyceride transfer protein (mtp), which is involved in the biosynthesis of apolipoprotein B (ApoB)-containing lipoproteins. By manipulating lipoprotein concentrations in zebrafish, we found that ApoB negatively regulates angiogenesis and that it is the ApoB protein particle, rather than lipid moieties within ApoB-containing lipoproteins, that is primarily responsible for this effect. Mechanistically, we identified downregulation of vascular endothelial growth factor receptor 1 (VEGFR1), which acts as a decoy receptor for VEGF, as a key mediator of the endothelial response to lipoproteins, and we observed VEGFR1 downregulation in hyperlipidemic mice. These findings may open new avenues for the treatment of lipoprotein-related vascular disorders.

References

Nov 1, 1977·Proceedings of the National Academy of Sciences of the United States of America·R ShiremanW R Fisher
Sep 9, 1993·The American Journal of Cardiology·P D Henry
Aug 5, 1997·Proceedings of the National Academy of Sciences of the United States of America·P J BabinB Thisse
Jul 22, 1998·Proceedings of the National Academy of Sciences of the United States of America·M RaabeS G Young
Aug 5, 1998·Proceedings of the National Academy of Sciences of the United States of America·S HiratsukaM Shibuya
Aug 15, 2000·Annual Review of Nutrition·N Berriot-VaroqueauxJ R Wetterau
Mar 7, 2001·Frontiers in Bioscience : a Journal and Virtual Library·S Fazio, M F Linton
Aug 9, 2002·Developmental Biology·Nathan D Lawson, Brant M Weinstein
Aug 27, 2002·Current Biology : CB·Hinrich HabeckUNKNOWN Tübingen 2000 screen consortium
Aug 28, 2003·The Journal of Biological Chemistry·Gregory S ShelnessRichard B Weinberg
Sep 5, 2003·Development·Sumio IsogaiBrant M Weinstein
Aug 1, 1959·Canadian Journal of Biochemistry and Physiology·E G BLIGH, W J DYER
Feb 13, 2004·Developmental Cell·Juanita L ThorpeSteven A Farber
Apr 16, 2004·Current Biology : CB·Jeffrey D Amack, H Joseph Yost
Dec 23, 2004·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Esther MarzaPatrick J Babin
May 19, 2005·Clinical Chemistry and Laboratory Medicine : CCLM·Kristiaan WoutersMarten H Hofker
May 30, 2006·Nature Medicine·Karina YanivBrant M Weinstein
Nov 28, 2006·Developmental Biology·Van N PhamBrant M Weinstein
Jun 5, 2007·Pediatric Dermatology·Gomathy SethuramanVinod K Sharma
Dec 7, 2007·EMBO Reports·Seppo Ylä-Herttuala, Kari Alitalo
Mar 12, 2008·Developmental Cell·Peter FraislPeter Carmeliet
May 8, 2008·Current Opinion in Lipidology·M Mahmood HussainIrani Khatun
Jul 29, 2008·Journal of Cellular and Molecular Medicine·Stefania NicoliMarco Presta
Dec 4, 2008·Progress in Lipid Research·Patrick J Babin, Geoffrey F Gibbons
Dec 19, 2008·Disease Models & Mechanisms·Aniket V GoreBrant M Weinstein
Jan 14, 2009·Nature Reviews. Genetics·Robert A Hegele
Sep 18, 2009·Developmental Cell·John C ChappellVictoria L Bautch
Mar 17, 2010·Nature·Carolina E HagbergUlf Eriksson
Jun 16, 2010·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Norio Takada, Bruce Appel
May 10, 2011·Methods in Cell Biology·Jennifer L AndersonSteven A Farber
Aug 2, 2011·Developmental Cell·Tomasz ZygmuntJesús Torres-Vázquez

❮ Previous
Next ❯

Citations

May 31, 2013·Nature·Longhou FangYury I Miller
Jun 4, 2013·Nature Cell Biology·Cyrus M GhajarMina J Bissell
Jul 3, 2013·Nature Cell Biology·Sara M Weis, David A Cheresh
Jan 15, 2013·Current Opinion in Lipidology·Petri I Mäkinen, Seppo Ylä-Herttuala
Jul 30, 2014·Mechanisms of Ageing and Development·Brian MeehanJanusz Rak
Jul 7, 2014·Trends in Endocrinology and Metabolism : TEM·Massimo M Santoro
Jan 28, 2015·Developmental Cell·Marc RenzSalim Abdelilah-Seyfried
Oct 8, 2013·Translational Research : the Journal of Laboratory and Clinical Medicine·Longhou FangYury I Miller
Dec 17, 2014·Journal of Pharmacological and Toxicological Methods·Juan ZhouChun-Qi Li
Oct 20, 2015·Developmental Biology·Michela Goi, Sarah J Childs
Mar 26, 2016·Frontiers in Physiology·Myra N ChávezJosé T Egaña
Dec 4, 2013·Critical Reviews in Clinical Laboratory Sciences·Tjerk de NijsJacqueline de Graaf
Apr 15, 2015·Journal of Inherited Metabolic Disease·Gina A SmithSreenivasan Ponnambalam
Jan 6, 2015·Cellular and Molecular Life Sciences : CMLS·Amnon Schlegel, Philipp Gut
Aug 27, 2013·Cell Metabolism·Katrien De BockPeter Carmeliet
May 13, 2014·Seminars in Cell & Developmental Biology·Annika SchuermannWiebke Herzog
Jan 13, 2015·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Amnon Schlegel
Jun 25, 2016·Journal of the American College of Cardiology·John T WilkinsDonald M Lloyd-Jones
Aug 6, 2016·Frontiers in Physiology·Raj Sewduth, Massimo M Santoro
Jul 28, 2016·Nature Reviews. Molecular Cell Biology·Michael SimonsLena Claesson-Welsh
Nov 3, 2016·Journal of the American Chemical Society·Anat AkivaSteve Weiner
Dec 21, 2016·Clinical and Translational Science·R A Farris, E T Price
Jan 11, 2017·Nature Communications·Raphael WildFerdinand le Noble
Jul 5, 2017·Zygote : the Biology of Gametes and Early Embryos·Ekaterina KondakovaVladimir Efremov
Jun 14, 2017·International Journal of Molecular Sciences·Megan YuYu-Min Kuo
Feb 6, 2018·Angiogenesis·Eugenia Manevitz-MendelsonShoshana Greenberger
Apr 19, 2018·Antioxidants & Redox Signaling·Katrin Schröder
Dec 7, 2017·Frontiers in Endocrinology·Vanessa H Quinlivan, Steven A Farber
Sep 23, 2016·Arteriosclerosis, Thrombosis, and Vascular Biology·Andrew J Morris, Susan S Smyth
Aug 27, 2016·Arteriosclerosis, Thrombosis, and Vascular Biology·Liron Gibbs-BarKarina Yaniv
Jul 11, 2014·Nature·Bart GhesquièrePeter Carmeliet
Oct 24, 2019·JAMA Cardiology·Allan D SnidermanBrian A Ference
Feb 21, 2013·Current Opinion in Endocrinology, Diabetes, and Obesity·Allan Sniderman, Peter O Kwiterovich

❮ Previous
Next ❯

Related Concepts

Related Feeds

Arterial-Venous in Development & Disease

Arterial-venous development may play a crucial role in cardiovascular diseases. Here is the latest research.

ApoE, Lipids & Cholesterol

Serum cholesterol, triglycerides, apolipoprotein B (APOB)-containing lipoproteins (very low-density lipoprotein (VLDL), immediate-density lipoprotein (IDL), and low-density lipoprotein (LDL), lipoprotein A (LPA)) and the total cholesterol/high-density lipoprotein (HDL) cholesterol ratio are all connected in diseases. Here is the latest research.