CCN1 Knockdown Suppresses Neointimal Hyperplasia in a Rat Artery Balloon Injury Model
Abstract
Objective— CCN1 (Cyr61) is an extracellular matrix-associated protein involved in cell proliferation and survival. CCN1 is bound to vascular smooth muscle cells (VSMCs) via integrins and is expressed in VSMCs in atherosclerotic lesions, suggesting involvement in the regulation of vascular smooth muscle cell (VSMC) proliferation and atherosclerosis. We hypothesized that knockdown of CCN1 may inhibit VSMC proliferation and suppress neointimal hyperplasia. Methods and Results— We examined the effect of the knockdown of CCN1 using rat cultured VSMCs and a rat balloon injury model. CCN1 stimulated adhesion and migration of VSMCs in a dose-dependent manner, and this was blocked by an antibody for integrin α 6 β 1 . Moreover, knockdown of endogenous CCN1 by lentiviral delivery of siRNA significantly inhibited proliferation of VSMCs and the uptake of 5-bromo-2′-deoxyuridine (BrdU). Replenishment with recombinant CCN1 reversed the effect of siRNA knockdown. Interestingly, knockdown of CCN1 significantly suppressed neointimal hyperplasia in a rat carotid artery balloon injury model at days 14 and 28 after injury. Gene transfer of CCN1 to smooth muscle reversed the effect of CCN1 knockdown on neointimal formation. These results suggest that endogenous CCN1 regulates proliferation of VSMCs and neointimal hyperplasia. Conclusion— Inhibition of CCN1 may provide a promising strategy for the prevention of restenosis after vascular interventions.
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Delivery of CCN1 via gene transfer reverses the reduction in neointimal hyperplasia caused by CCN1 suppression.
“Suppression of CCN1 expression by either small interfering RNA or FOXO3a-mediated transcriptional repression results in reduced neointimal hyperplasia after balloon angioplasty, an effect that is reversed by delivery of CCN1 via gene transfer [136,137].”
From CCN1/CYR61: the very model of a modern matricellular protein (2011) · cites this paper as [137]
Suppression of CCN1 expression by siRNA or FOXO3a-mediated transcriptional repression reduces neointimal hyperplasia after balloon angioplasty.
“Suppression of CCN1 expression by either small interfering RNA or FOXO3a-mediated transcriptional repression results in reduced neointimal hyperplasia after balloon angioplasty, an effect that is reversed by delivery of CCN1 via gene transfer [136,137].”
From CCN1/CYR61: the very model of a modern matricellular protein (2011) · cites this paper as [137]
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- Authors
- Matsumae, H., Yoshida, Y., Ono, K., Togi, K., Inoue, K., Furukawa, Y., Nakashima, Y., Kojima, Y., Nobuyoshi, M., Kita, T., & Tanaka, M.
- Affiliations
- Kyoto University (JP)
- ORCID
- Venue
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Published
- 2008-06
- Volume
- 28
- Issue
- 6
- Pages
- 1077-1083
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- OpenAlex
- W2100488895
- Cited by
- 59
- References
- 35
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 4 · 2020: 3 · 2019: 4 · 2018: 3 · 2017: 3 · 2016: 7 · 2015: 3 · 2014: 5 · 2013: 1 · 2012: 2
- FWCI
- 2.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- Kyoto University Research Information Repository (Kyoto University) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connective Tissue Growth Factor Research
- Health Sciences › Medicine › Surgery › Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Keywords
- CYR61, intimal hyperplasia, vascular smooth muscle cell proliferation, alpha6beta1 integrin, balloon injury, restenosis, siRNA knockdown, gene transfer, carotid artery, extracellular matrix, atherosclerosis
- MeSH terms
- Angioplasty, Balloon, Animals, Cell Adhesion, Cell Movement, Cells, Cultured, Disease Models, Animal, Hyperplasia, Male, Muscle, Smooth, Vascular, Down-Regulation, Integrins, Rats, Sprague-Dawley, Tunica Intima, Immediate-Early Proteins, RNA, Small Interfering, Intercellular Signaling Peptides and Proteins, Cell Proliferation, Rats, Cysteine-Rich Protein 61
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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