The Response-to-Retention Hypothesis of Early Atherogenesis

Williams, Kevin Jon; Tabas, Ira

doi:10.1161/01.atv.15.5.551

Cited by 1,413Atherosclerosis and Cardiovascular DiseasesCholesterol and Lipid MetabolismNitric Oxide and Endothelin Effects

The Response-to-Retention Hypothesis of Early Atherogenesis

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Williams, Kevin Jon, Tabas, Ira·1995·Arteriosclerosis, Thrombosis, and Vascular Biology

DOI 10.1161/01.atv.15.5.551PMC PMC2924812

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Retention of lipoproteins in the arterial extracellular matrix is a critical step in atherogenesis in which lipoproteins with higher affinity for arterial proteoglycans are more atherogenic.
“The retention of lipoproteins in the arterial extracellular matrix is a critical step in atherogenesis in which lipoproteins with higher affinity for arterial proteoglycans are more atherogenic (55, 56).”
From Role of the N- and C-Terminal Domains in Binding of Apolipoprotein E Isoforms to Heparan Sulfate and Dermatan Sulfate: A Surface Plasmon Resonance Study (2008) · cites this paper as [55]
The ECM has a central role in initiation of atherosclerosis, primarily through the interaction between the negatively charged side chains of proteoglycans with positively charged apolipoproteins, which leads to the retention of plasma-derived lipoproteins.
“The ECM has a central role in initiation of atherosclerosis, primarily through the interaction between the negatively charged side chains of proteoglycans (particularly chondroitin sulphate of biglycan and versican and heparin sulphate of perlecan 110 ) with positively charged apolipoproteins (especially apolipoprotein B) , which leads to the retention of plasma-derived lipoproteins 101,111 - as”
From Vascular smooth muscle cells in atherosclerosis (2019) · cites this paper as [113]
Interaction of apoB-containing lipoproteins with intimal extracellular proteoglycans inhibits their movement, producing higher subendothelial concentrations in the intima than in other tissues.
“the interaction of apoB-containing lipoproteins (the non-HDL lipoproteins) with intimal extracellular proteoglycans (referred to as retention)1,43,44 inhibits the movement of the lipoproteins, thereby resulting in much higher subendothelial concentrations of these lipoproteins in the intima than in any other tissue45.”
From Inflammation and its resolution in atherosclerosis: mediators and therapeutic opportunities (2019) · cites this paper as [1]
Atherosclerosis is a low-grade chronic inflammatory disease of the arterial wall triggered by subendothelial retention of apolipoprotein B-containing lipoproteins.
“Atherosclerosis is a disease characterized by low-grade, chronic inflammation of the arterial wall and is triggered by the subendothelial retention of plasma-derived, apolipoprotein B (apoB)-containing lipoproteins in the affected inner layer of the arterial wall, the intima1–3.”
From Inflammation and its resolution in atherosclerosis: mediators and therapeutic opportunities (2019) · cites this paper as [1]

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Authors: Williams, K. J., & Tabas, I.
Affiliations: Thomas Jefferson University (US)
ORCID: Williams, Kevin Jon
Tabas, Ira
Venue: Arteriosclerosis, Thrombosis, and Vascular Biology
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 1995-05
Volume: 15
Issue: 5
Pages: 551-561
ISSN: 1079-5642 (ISSN-L)
1524-4636
DOI: 10.1161/01.atv.15.5.551
PMC: PMC2924812
OpenAlex: W1968171440
Cited by: 1,413
References: 240
Citations by year: 2026: 27 · 2025: 34 · 2024: 37 · 2023: 40 · 2022: 42 · 2021: 39 · 2020: 55 · 2019: 47 · 2018: 42 · 2017: 41 · 2016: 59 · 2015: 73 · 2014: 60 · 2013: 56 · 2012: 60
FWCI: 12.35
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: American Heart Association
National Institutes of Health (5p50hl021006-17, 5r01hl039703-08)
Genentech
National Heart, Lung, and Blood Institute (HL 38956, HL-39703, HL 21006, R01HL038956)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
Keywords: atherosclerosis initiation, plaque retention, endothelial dysfunction
MeSH terms: Animals, Arteries, Arteriosclerosis, Humans, Lipoproteins, LDL, Models, Biological, Proteoglycans

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The Response-to-Retention Hypothesis of Early Atherogenesis

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