Vascular Discovery Scientic Sessions 2025  /  12. Early Career Investigator Award Competition: Irvine H. Page Junior Faculty Research Award & Kenneth M. Brinkhous Early Career Investigator Award in Thrombosis  /  The N-terminus of Apolipoprotein B mediates the interaction of atherogenic lipoproteins with endothelial cells
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American Heart Association

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The N-terminus of Apolipoprotein B mediates the interaction of atherogenic lipoproteins with endothelial cells

Abstract Body: Apolipoprotein B (APOB) containing lipoproteins contribute to atherosclerosis by entering the arterial wall through the endothelial cell surface receptors scavenger receptor-BI (SR-BI) and activin receptor-like kinase 1 (ALK1). We used N-terminal fragments of APOB, molecular modeling, and site-directed mutagenesis to identify and block the binding of chylomicrons and LDL to these receptors in cells and mice. We discovered that different regions interact with SR-BI and ALK1. A fragment of APOB, comprising 18% of the N-terminal sequence (APOB18), reduced the uptake and transport of both chylomicrons and LDL by endothelial cells. Importantly, overexpressing APOB18 decreased atherosclerosis in hypercholesterolemic mice. These findings identify the N-terminal region of APOB as the cause of atherosclerosis and illustrate an approach to treating or preventing vascular disease
  • Gonzalez, Ainara  ( New York University Langone Health , New York , New York , United States )
  • Davidson, Nicholas  ( Washington University School of Medicine , St Louis , Missouri , United States )
  • Kanter, Jenny  ( UNIVERSITY OF WASHINGTON , Seattle , Washington , United States )
  • Bornfeldt, Karin  ( University of Washington , Seattle , Washington , United States )
  • Fisher, Edward  ( New York University Langone Health , New York , New York , United States )
  • Lee, Warren  ( Keenan Centre for Biomedical Research , Toronto , Ontario , Canada )
  • Madl, Tobias  ( University of Graz , Graz , Austria )
  • Hussain, Mahmood  ( NYU LI School of Medicine , Mineola , New York , United States )
  • Goldberg, Ira  ( NEW YORK UNIVERSITY , New York , New York , United States )
  • Younis, Waqas  ( New York University Langone Health , New York , New York , United States )
  • Nasias, Dimitrios  ( New York University Langone Health , New York , New York , United States )
  • Ho, Tse Wing Winnie  ( Keenan Centre for Biomedical Research , Toronto , Ontario , Canada )
  • Anaganti, Narasimha  ( HBNI, MUMBAI , Mumbai , India )
  • Valmiki, Swati  ( New York University Long Island School of Medicine , Mineola , New York , United States )
  • Gjini, Jana  ( New York University Langone Health , New York , New York , United States )
  • Kore, Rufina  ( New York University Langone Health , New York , New York , United States )
  • Nikain, Carmen  ( New York University Langone Health , New York , New York , United States )
    • Author Disclosures:
    Ainara Gonzalez: DO NOT have relevant financial relationships | Nicholas Davidson: No Answer | Jenny Kanter: DO NOT have relevant financial relationships | Karin Bornfeldt: No Answer | Edward Fisher: No Answer | Warren Lee: No Answer | Tobias Madl: No Answer | Mahmood Hussain: DO NOT have relevant financial relationships | Ira Goldberg: DO NOT have relevant financial relationships | Waqas Younis: No Answer | Dimitrios Nasias: No Answer | Tse Wing Winnie Ho: No Answer | Narasimha Anaganti: DO NOT have relevant financial relationships | Swati Valmiki: No Answer | Jana Gjini: No Answer | Rufina Kore: No Answer | Carmen Nikain: No Answer
Meeting Info:

Vascular Discovery Scientic Sessions 2025

2025

Baltimore, MD

Session Info:

12. Early Career Investigator Award Competition: Irvine H. Page Junior Faculty Research Award & Kenneth M. Brinkhous Early Career Investigator Award in Thrombosis

Thursday, 04/24/2025 , 01:00PM - 03:00PM

Oral

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