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Cited by 305Atherosclerosis and Cardiovascular DiseasesCell Adhesion Molecules ResearchLipoproteins and Cardiovascular Health

Apolipoprotein CIII Induces Expression of Vascular Cell Adhesion Molecule-1 in Vascular Endothelial Cells and Increases Adhesion of Monocytic Cells

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Kawakami, Akio, Aikawa, Masanori, Alcaide, Pilar, Luscinskas, Francis W., Libby, Peter, Sacks, Frank M.·2006·Circulation
DOI 10.1161/circulationaha.106.622514
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Abstract

Background— Activation of vascular endothelial cells (ECs) plays an important role in atherogenesis and plaque instability. Lipoproteins containing apolipoprotein CIII (apoCIII) predict coronary heart disease (CHD). We recently reported that apoCIII has a proinflammatory effect on human monocytes. In this study, we looked for a direct effect of apoCIII on EC expression of adhesion molecules, leading to monocytic cell adhesion. Methods and Results— Treatment of ECs with apoCIII or apoCIII-rich VLDL caused human monocytic THP-1 cells to adhere to them under static condition or under laminar sheer stress (1.0 dyne/cm 2 ). ApoCIII increased EC expression of vascular cell adhesion molecule-1 (VCAM-1) protein and intercellular cell adhesion molecule-1 (ICAM-1) protein (4.9±1.5-fold and 1.4±0.5-fold versus control, respectively). Furthermore, apoCIII remarkably increased membrane-bound protein kinase C (PKC) β in ECs, indicating activation. A selective inhibitor of PKCβ prevented the rise in VCAM-1 and THP-1 cell adhesion to ECs. Moreover, exposure of ECs to apoCIII induced nuclear factor-κB (NF-κB) activation. PKCβ inhibition abolished apoCIII-induced NF-κB activation, and NF-κB inhibition reduced expression of VCAM-1, each resulting in reduced THP-1 cell adhesion. ApoCIII-rich VLDL also activated PKCβ and NF-κB in ECs and increased expression of VCAM-1. Pretreatment of ApoCIII-rich VLDL with anti-apoCIII neutralizing antibody abolished its effect on PKCβ activation. Conclusions— Our findings provide the first evidence that apoCIII increases VCAM-1 and ICAM-1 expression in ECs by activating PKCβ and NF-κB, suggesting a novel mechanism for EC activation induced by dyslipidemia. Therefore, apoCIII-rich VLDL may contribute directly to atherogenesis by activating ECs and recruiting monocytes to them.

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  • VLDL and LDL particles carrying APOC-III-but not those lacking APOC-III-initiate atherosclerosis by promoting endothelial injury and monocyte adhesion.

    “Moreover, VLDL and LDL particles carrying APOC-III—but not those lacking APOC-III—initiate atherosclerosis by promoting endothelial injury and monocyte adhesion [28, 29].”

    From The Efficacy and Safety of Plozasiran on Lipid Profile in Dyslipidemic Disorders: A Systematic Review and Meta-Analysis (2026) · cites this paper as [29]

    The Results section (“VLDL CIII+ Induces Adhesion of THP-1 Cells to ECs”; page unavailable) reports that APOC-III-containing VLDL increased monocytic-cell adhesion to endothelial cells, whereas VLDL lacking APOC-III did not. The Abstract and Discussion describe endothelial activation and say APOC-III-rich VLDL *may contribute* to atherogenesis. This paper does not establish that both VLDL and LDL initiate atherosclerosis through endothelial injury; its direct endothelial comparison concerns VLDL, and it reports activation rather than injury. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

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Authors
Kawakami, A., Aikawa, M., Alcaide, P., Luscinskas, F. W., Libby, P., & Sacks, F. M.
Affiliations
Brigham and Women's Hospital (US)
ORCID
Venue
Circulation
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2006-08-15
Volume
114
Issue
7
Pages
681-687
ISSN
  • 0009-7322 (ISSN-L)
  • 1524-4539
DOI
10.1161/circulationaha.106.622514
OpenAlex
W2072567581
Cited by
305
References
2
Citations by year
2026: 9 · 2025: 12 · 2024: 18 · 2023: 18 · 2022: 11 · 2021: 17 · 2020: 23 · 2019: 8 · 2018: 14 · 2017: 19 · 2016: 16 · 2015: 16 · 2014: 12 · 2013: 19 · 2012: 13
FWCI
5.31
Type
journal article
Language
en
Open access
Locations
  • Circulation (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Donald W. Reynolds Foundation
  • Pfizer
  • Japan Heart Foundation
  • National Heart, Lung, and Blood Institute (P50HL056985, HL-80472, R01HL069376, HL53393, HL69376, HL56985, P01HL036028, R01HL080472, HL36028, HL-48743, P01HL048743)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
  • Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
Keywords
apolipoprotein C-III, VCAM-1, ICAM-1, protein kinase C beta, NF-κB activation, VLDL, dyslipidemia, atherogenesis, monocyte recruitment, laminar shear stress
MeSH terms
NF-KappaB Inhibitor alpha, Apolipoproteins C, Cell Adhesion, Cell Line, Cells, Cultured, Humans, Monocytes, Protein Kinase C, Cholesterol, VLDL, NF-kappa B, Intercellular Adhesion Molecule-1, Vascular Cell Adhesion Molecule-1, Integrin beta1, I-kappa B Proteins, Endothelial Cells, Dyslipidemias, Atherosclerosis, Apolipoprotein C-III

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