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Cited by 384

The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index.

Statins Alter Smooth Muscle Cell Accumulation and Collagen Content in Established Atheroma of Watanabe Heritable Hyperlipidemic Rabbits

Open access
Fukumoto, Yoshihiro, Libby, Peter, Rabkin, Elena, Hill, Christopher C., Enomoto, Makoto, Hirouchi, Yasuhiko, Shiomi, Masashi, Aikawa, Masanori·2001·Circulation
DOI 10.1161/01.cir.103.7.993
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Abstract

Background —Acute coronary syndromes often result from rupture of vulnerable plaques. The collagen content of plaques probably regulates their stability. This study tested whether HMG-CoA reductase inhibitors (statins) alter interstitial collagen gene expression or matrix metalloproteinase (MMP) levels in rabbit atheroma. Methods and Results —We administered equihypocholesterolemic doses of pravastatin (a hydrophilic statin, 50 mg · kg −1 · d −1 , n=9), fluvastatin (a cell-permeant lipophilic statin, 20 mg · kg −1 · d −1 , n=10), or placebo (n=10) to mature Watanabe heritable hyperlipidemic rabbits for 52 weeks. The fluvastatin group achieved a much higher peak plasma concentration (23.7 μmol/L) than did the pravastatin group (1.3 μmol/L) under these conditions. Immunohistochemistry revealed that MMP-1, MMP-3, and MMP-9 expression by macrophages in the intima was lower in both the pravastatin and fluvastatin groups than in the placebo group, whereas there was no difference in macrophage numbers. Numbers of intimal smooth muscle cells (SMCs) (identified by immunohistochemistry) and expression of type I procollagen mRNA (detected by in situ hybridization), however, were significantly higher in the pravastatin group than in the fluvastatin group. Treatment with pravastatin, but not fluvastatin, preserved interstitial collagen content in vivo (detected by picrosirius red polarization). In vitro, fluvastatin, but not pravastatin, decreased numbers of rabbit and human aortic SMCs without altering procollagen I mRNA expression. Conclusions —This study showed that statins can reduce MMP expression in atheroma and that cell-permeant statins can decrease SMC number and collagen gene expression in vivo.

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Metadata

Authors
Fukumoto, Y., Libby, P., Rabkin, E., Hill, C. C., Enomoto, M., Hirouchi, Y., Shiomi, M., & Aikawa, M.
Venue
Circulation
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2001-02-20
Volume
103
Issue
7
Pages
993-999
ISSN
  • 0009-7322 (ISSN-L)
  • 1524-4539
DOI
10.1161/01.cir.103.7.993
OpenAlex
W2063842926
Cited by
384
References
32
FWCI
37.88
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Statins Alter Smooth Muscle Cell Accumulation and Collagen Content in Established Atheroma of Watanabe Heritable Hyperlipidemic Rabbits. https://app.cochat.ai/papers/10.1161/01.cir.103.7.993
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Fukumoto, Y., Libby, P., Rabkin, E., Hill, C. C., Enomoto, M., Hirouchi, Y., Shiomi, M., & Aikawa, M. (2001). Statins Alter Smooth Muscle Cell Accumulation and Collagen Content in Established Atheroma of Watanabe Heritable Hyperlipidemic Rabbits. Circulation. https://doi.org/10.1161/01.cir.103.7.993

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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