Pathologic intimal thickening in human atherosclerosis is formed by extracellular accumulation of plasma-derived lipids and dispersion of intimal smooth muscle cells
Abstract
Background and aims Pathologic intimal thickening (PIT) is an important stage of atherosclerosis that leads to atheroma. The present study aimed to clarify the pathogenesis of PIT in humans.Methods Coronary arteries were obtained from 43 autopsy subjects aged 15-49 years. Non-atherosclerotic intima and atherosclerotic intimal lesions were classified into four groups, i.e. diffuse intimal thickening, fatty infiltration, fatty streak, and PIT, and the number and density of macrophages and smooth muscle cells (SMCs) were determined. Components of the lesions and proliferative and apoptotic activities of macrophages and SMCs were investigated by immunohistochemistry and TUNEL assay.Results Extracellular lipids accumulated mildly in the fatty infiltration and fatty streak, and abundantly in the PIT to form the lipid pool. The extracellular lipids co-localized with apolipoprotein B and fibrinogen. Macrophage foam cells accumulated in the fatty streak and PIT, but no TUNEL-positive macrophages were detected in any lesion. No significant difference in the number of SMCs was found between the four groups, but the density of SMCs decreased in the fatty streak and PIT. The decrease correlated with an increase in the number of macrophages, and the accumulation of extracellular lipids in the lipid pool. Neither Ki-67-positive nor TUNEL-positive SMCs were detected in any lesion.Conclusions In PIT in human atherosclerosis, the lipid pool is formed by infiltration and deposition of plasma-derived lipids. Intimal SMCs are dispersed in association with macrophage infiltration and lipid pool formation without undergoing significant proliferation or death.
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A recent study comparing DITs to PITs found extra-cellular lipid deep in the plaque, colocalising with αSMA-positive cells, ApoB, biglycan and versican, but not the more superficial CD68 positive cells.
“Further evidence for this series of events was provided by a recent study comparing DITs to PITs, in which extra-cellular lipid was found deep in the plaque, colocalising with α SMA-positive cells, ApoB, biglycan and versican, but not the more superficial (closer to the lumen) CD68 positive cells (likely macrophages) 116 .”
From Vascular smooth muscle cells in atherosclerosis (2019) · cites this paper as [116]
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Sakamoto, A., Sato, Y., Finn, A. V., & Virmani, R. (2020) · Contemporary cardiology · doi:10.1007/978-3-030-46725-8_2 · Cited by 1 · see citing works
Intimal Growth in Cylindrical Arteries: Impact of Anisotropic Growth on Glagov RemodelingPreprint
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Watanabe, T., & Fan, J. (2025) · Springer eBooks · doi:10.1007/978-981-96-3675-4_2
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- Authors
- Nakagawa, K., & Nakashima, Y.
- Affiliations
- Kyushu University (JP)
- Japanese Red Cross Fukuoka Hospital (JP)
- Corresponding author
- Nakagawa, Kazunori
- Nakashima, Yutaka
- ORCID
- Nakashima, Yutaka
- Venue
- Atherosclerosis
- Publisher
- Elsevier BV
- Published
- 2018-07
- Volume
- 274
- Pages
- 235-242
- ISSN
- 0021-9150 (ISSN-L)
- OpenAlex
- W2792141776
- Cited by
- 70
- References
- 39
- Citations by year
- 2026: 2 · 2025: 12 · 2024: 6 · 2023: 5 · 2022: 9 · 2021: 11 · 2020: 9 · 2019: 13 · 2018: 3
- FWCI
- 3.88
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Atherosclerosis (publishedVersion)
- PubMed (publishedVersion)
- Funders
- JSPS (JP26670177)
- The Foundation for the Advancement of Clinical Medicine
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Keywords
- intimal smooth muscle cells, macrophage infiltration, foam cells, apolipoprotein B, fibrinogen, coronary artery lesions, atherosclerotic plaque, cell proliferation, apoptosis
- MeSH terms
- Adolescent, Adult, Autopsy, Coronary Artery Disease, Coronary Vessels, Female, Fibrinogen, Foam Cells, Humans, Lipids, Male, Middle Aged, Muscle, Smooth, Vascular, Phenotype, Apoptosis, Disease Progression, Myocytes, Smooth Muscle, Apolipoprotein B-100, Young Adult, Plaque, Atherosclerotic, Neointima
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