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Cited by 524Lipoproteins and Cardiovascular HealthCholesterol and Lipid MetabolismAtherosclerosis and Cardiovascular Diseases

The central role of arterial retention of cholesterol-rich apolipoprotein-B-containing lipoproteins in the pathogenesis of atherosclerosis: a triumph of simplicity

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Borén, Jan, Williams, Kevin Jon·2016·Current Opinion in Lipidology
DOI 10.1097/mol.0000000000000330
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Abstract

Purpose of review: Today, it is no longer a hypothesis, but an established fact, that increased plasma concentrations of cholesterol-rich apolipoprotein-B (apoB)-containing lipoproteins are causatively linked to atherosclerotic cardiovascular disease (ASCVD) and that lowering plasma LDL concentrations reduces cardiovascular events in humans. Here, we review evidence behind this assertion, with an emphasis on recent studies supporting the ‘response-to-retention’ model – namely, that the key initiating event in atherogenesis is the retention, or trapping, of cholesterol-rich apoB-containing lipoproteins within the arterial wall. Recent findings: New clinical trials have shown that ezetimibe and anti-PCSK9 antibodies – both nonstatins – lower ASCVD events, and they do so to the same extent as would be expected from comparable plasma LDL lowering by a statin. These studies demonstrate beyond any doubt the causal role of apoB-containing lipoproteins in atherogenesis. In addition, recent laboratory experimentation and human Mendelian randomization studies have revealed novel information about the critical role of apoB-containing lipoproteins in atherogenesis. New information has also emerged on mechanisms for the accumulation in plasma of harmful cholesterol-rich and triglyceride-rich apoB-containing remnant lipoproteins in states of overnutrition. Like LDL, these harmful cholesterol-rich and triglyceride-rich apoB-containing remnant lipoprotein remnants become retained and modified within the arterial wall, causing atherosclerosis. Summary: LDL and other cholesterol-rich, apoB-containing lipoproteins, once they become retained and modified within the arterial wall, cause atherosclerosis. This simple, robust pathophysiologic understanding may finally allow us to eradicate ASCVD, the leading killer in the world.

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Crossref · 10.1097/mol.0000000000000330

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  • TRLs and their remnants actively participate in lipid retention, cellular activation, and vascular inflammation, contributing to atherosclerotic disease progression.

    “TRLs not only transport lipids but actively participate in a complex interplay of lipid retention, cellular activation, and vascular inflammation, all fundamental drivers of atherosclerotic disease progression [14, 15].”

    From Targeting triglycerides for cardiovascular risk reduction (2026) · cites this paper as [14]

  • All ApoB-containing lipoproteins less than 70 nm in diameter, including triglyceride-rich VLDL remnants and LDL particles, freely flux across the endothelial barrier where they can become retained in the artery wall.

    “All ApoBcontaining lipoproteins less than 70 nm in diameter, including triglyceride-rich VLDL remnants and LDL particles, freely flux across the endothelial barrier where they can become retained in the artery wall.24”

    From Association of Triglyceride-Lowering <i>LPL</i> Variants and LDL-C–Lowering <i>LDLR</i> Variants With Risk of Coronary Heart Disease (2019) · cites this paper as [24]

  • Retained lipoproteins bound to the arterial intima extracellular matrix are susceptible to modification by intimal oxidizing agents, proteases, and lipases.

    “The retained lipoproteins (that is, those bound to the extracellular matrix of the arterial intima) are susceptible to modification by intimal oxidizing agents, proteases and lipases43,46,47.”

    From Inflammation and its resolution in atherosclerosis: mediators and therapeutic opportunities (2019) · cites this paper as [43]

  • 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 [43]

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Authors
Borén, J., & Williams, K. J.
Affiliations
Sahlgrenska University Hospital (SE)
Corresponding author
Borén, Jan
ORCID
Venue
Current Opinion in Lipidology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2016-10
Volume
27
Issue
5
Pages
473-483
ISSN
  • 0957-9672 (ISSN-L)
  • 1473-6535
DOI
10.1097/mol.0000000000000330
OpenAlex
W2501649131
Cited by
524
References
96
Citations by year
2026: 31 · 2025: 57 · 2024: 61 · 2023: 64 · 2022: 72 · 2021: 77 · 2020: 61 · 2019: 44 · 2018: 40 · 2017: 13 · 2016: 4
FWCI
6.68
Type
journal article
Language
en
Open access
Licence
Locations
  • Current Opinion in Lipidology (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
Keywords
atherosclerosis, apolipoprotein B, cholesterol-rich lipoproteins, LDL cholesterol, atherogenesis, ezetimibe, PCSK9 inhibitors, overnutrition, cardiovascular disease prevention, Mendelian randomization
MeSH terms
Animals, Apolipoproteins B, Arteries, Cholesterol, Humans, Risk Factors, Atherosclerosis, Protein Aggregates

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