Cytokines and growth factors positively and negatively regulate interstitial collagen gene expression in human vascular smooth muscle cells.
Open accessAbstract
Human atheromas accumulate extracellular matrix proteins such as collagen types I and III. We tested whether cytokines or growth factors produced by cells found in human atherosclerotic plaques alter collagen gene expression in vascular smooth muscle cells (VSMCs), which produce the blood vessel matrix. Interleukin-1 (IL-1, 1-10 ng/ml) modestly increased the synthesis of collagens I and III (measured by tritiated proline incorporation into specific electrophoretic bands), whereas transforming growth factor-beta (TGF-beta) or platelet-derived growth factor (PDGF) markedly stimulated production of these interstitial collagens. Interferon gamma (IFN-gamma), a product of activated T cells found in atheromas, selectively alters several VSMC functions. For example, this cytokine reduces growth of VSMCs, decreases alpha-actin gene expression, and induces VSMC expression of class II histocompatibility antigens. We report here that IFN-gamma also inhibits basal as well as IL-1-, PDGF-, or TGF-beta-stimulated collagen I and III synthesis by human VSMCs. TGF-beta, the most potent stimulator of collagen synthesis studied here, raised the level of collagen III mRNA in VSMCs 4.8-fold (determined by densitometry of Northern blots), whereas exposure to both TGF-beta and IFN-gamma reduced this mRNA to 0.5 of basal level. Locally produced cytokines and growth factors may thus modify matrix accumulation during atherogenesis by stimulating or suppressing expression of interstitial collagen mRNA and protein by VSMCs.
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In vitro studies, including proteomic analysis of the secretome of lipid-loaded VSMCs and induction of collagen synthesis by VSMCs in culture by TGFβ, PDGF, IL-1, AngII, cholesterol, homocysteine and mechanical stretch, provide further evidence that VSMCs are the major source of collagens.
“Further evidence that VSMCs are the major source of collagens comes from studies in vitro , including proteomic analysis of the secretome of lipid-loaded VSMCs 109 and induction of collagen synthesis by VSMCs in culture by TGFβ , PDGF, IL-1, AngII, cholesterol, homocysteine and mechanical stretch 144,145”
From Vascular smooth muscle cells in atherosclerosis (2019) · cites this paper as [144]
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- Authors
- Amento, E. P., Ehsani, N., Palmer, H., & Libby, P.
- Affiliations
- Genentech (US)
- ORCID
- Venue
- Arteriosclerosis and Thrombosis: A Journal of Vascular Biology
- Published
- 1991-09
- Volume
- 11
- Issue
- 5
- Pages
- 1223-1230
- ISSN
- 1049-8834 (ISSN-L)
- OpenAlex
- W2099789417
- Cited by
- 609
- References
- 49
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 9 · 2023: 14 · 2022: 16 · 2021: 13 · 2020: 14 · 2019: 17 · 2018: 14 · 2017: 21 · 2016: 12 · 2015: 25 · 2014: 21 · 2013: 18 · 2012: 18
- FWCI
- 4.88
- Type
- journal article
- Language
- en
- Open access
- green
- nrs.harvard.edu
- Licence
- cc-by
- Locations
- Arteriosclerosis and Thrombosis A Journal of Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Funders
- National Heart, Lung, and Blood Institute (HL-34636)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Keywords
- vascular smooth muscle cells, collagen gene expression, type I collagen, type III collagen, cytokines, growth factors, interferon-gamma, interleukin-1, TGF-beta, platelet-derived growth factor, extracellular matrix, atherosclerosis, atherosclerotic plaque, alpha-actin, class II histocompatibility antigens
- MeSH terms
- Arteriosclerosis, Cells, Cultured, Collagen, Electrophoresis, Polyacrylamide Gel, Gene Expression Regulation, Growth Substances, Humans, Indomethacin, Interferon-gamma, Interleukin-1, Muscle, Smooth, Vascular, Platelet-Derived Growth Factor, Recombinant Proteins, RNA, Messenger, Blotting, Northern, Cytokines, Transforming Growth Factor beta
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