Thrombospondin-1 (TSP-1) is functionally important to intimal hyperplasia (IH) development. Statin drugs have beneficial pleiotropic effects, including reduced IH; however, the effect of statins on IH in a TSP-1-independent setting is unknown.
Statins will be less effective in attenuating IH after vascular injury in TSP-1-null (Thbs1(-/-)) mice compared with wild-type (WT) mice.
Carotid artery ligation was performed on WT and Thbs1(-/-) mice. Each strain was divided into two groups: no statin control or standard chow containing fluvastatin (10 or 40 mg/kg/d). After 28 d, analysis included morphometric analysis and real-time quantitative reverse transcription polymerase chain reaction on the arteries and enzyme-linked immunosorbent assay on plasma (TSP-1 WT, TSP-2 WT, and Thbs1(-/-)). Comparisons were made by analysis of variance, with P < 0.05 considered significant.
In no statin controls, WT mice had more IH than Thbs1(-/-) mice (0.46 ± 0.09 versus 0.15 ± 0.04). Fluvastatin reduced IH in the WT (0.46 ± 0.09 versus 0.23 ± 0.06), but not in Thbs1(-/-) groups (0.15 ± 0.04 versus 0.22 ± 0.07). No difference in IH existed between Thbs1(-/-) no statin controls and fluvastatin WT and Thbs1(-/-) groups. Statin dose did not affect IH. TSP-1 plasma levels were increased in fluvastatin WT. TSP-2 levels were decreased in fluvastatin WT and elevated in fluvastatin Thbs1(-/-). Fluvastatin had no effect on tissue Thbs1 or Thbs2 gene expression.
TSP-1 is necessary for robust IH after arterial injury. Because fluvastatin had no effect on IH in Thbs1(-/-), the data suggest that the statin effect on IH may be largely TSP-1 dependent. Both statins and the presence of TSP-1 affect TSP-1 and TSP-2 plasma levels.
Pharmacology, Toxicology and Pharmaceutical Science
1
14%
Unknown
3
43%
Attention Score in Context
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This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 14 October 2016.
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