Related Experiment Video
Updated: Jun 17, 2026
Implantation of Human-Sized Coronary Stents into Rat Abdominal Aorta Using a Trans-Femoral Access
Published on: November 19, 2020
Hemin prevents in-stent stenosis in rat and rabbit models by inducing heme-oxygenase-1
Jean-Marc Hyvelin1, Blandine Maurel, Rustem Uzbekov
1Laboratoire de Physiopathologie de la Paroi Artérielle, EA3852, IFR135, Faculté de Médecine, Université François Rabelais Tours, France. hyvelin.jean-marc@neuf.fr
Insights
Hemin treatment, a heme oxygenase-1 inducer, reduced in-stent stenosis after stenting without affecting re-endothelialization. This suggests HO-1 is a therapeutic target for preventing restenosis.
Area of Science:
- Cardiovascular Research
- Biomedical Engineering
- Pharmacology
Background:
- Drug-eluting stents (DES) improve percutaneous coronary intervention but raise concerns about late stent thrombosis.
- Heme oxygenase-1 (HO-1) offers cytoprotective effects and limits smooth muscle cell proliferation.
- Research is exploring therapeutics to enhance vascular healing post-stenting.
Purpose of the Study:
- To evaluate hemin, a potent HO-1 inducer, for reducing in-stent stenosis.
- To determine if hemin treatment compromises re-endothelialization after stenting.
- To investigate the role of HO-1 in preventing post-stent restenosis.
Main Methods:
- Hemin or vehicle treatment in stented rat aorta and rabbit iliac arteries.
- Histologic, electron microscopy, and protein analysis at 7-28 days post-stenting.
- Assessment of HO-1 induction, cellular proliferation, and re-endothelialization.
Main Results:
- Hemin treatment significantly reduced neointima growth in both rat and rabbit models.
- HO-1 expression was increased by hemin, limiting inflammatory and proliferative cellular events.
- Beneficial effects were blocked by an HO inhibitor but mimicked by a carbon monoxide donor.
Conclusions:
- Heme oxygenase-1 plays a crucial role in limiting in-stent stenosis.
- Hemin demonstrates therapeutic potential for preventing post-stent restenosis.
- HO-1 represents a promising new therapeutic target in cardiovascular interventions.
Objective:
The introduction of drug-eluting stents (DES) has largely added benefit to the percutaneous coronary intervention. Questions about the long-term safety of DES have been raised, however, particularly with respect to late stent thrombosis. Research efforts are now being directed toward therapeutics that can impede smooth muscle proliferation and promote vascular healing. Emerging data suggest that heme oxygenase-1 (HO-1), an inducible oxidoreductase enzyme system, can exert cytoprotective effects on endothelial cells and limit smooth muscle cell proliferation. We assessed the ability of hemin, a potent HO-1 inducer, to reduce in-stent stenosis without compromising re-endothelialization.
Methods:
Rat aorta and rabbit iliac arteries were stented. Animals received ongoing treated with intraperitoneal hemin (50 mg/kg) or vehicle. At 7 to 28 days after surgery, stented arterial segments were collected and processed for histologic, electron microscopy, or protein analysis.
Results:
In both models, treatment with hemin reduced neointima growth without compromising re-endothelialization of the stented arteries. In the rat aorta, analysis of protein expression at 7 and 28 days after stenting revealed that hemin increased HO-1 expression and limited the early inflammatory, apoptotic, and proliferative cellular events that are common to in-stent stenosis. Hemin treatment decreased the expression of the Ki-67 protein and the activity of key regulators of smooth muscle cell proliferation, including p42/44, RhoA, and up-regulated the expression of cyclin-dependent kinase inhibitors. The beneficial effects of hemin were abolished in the presence of tin-protoporphyrin IX, an HO inhibitor. Finally, treatment with tricarbonylchloro(glycinato)ruthenium(II), a carbon monoxide donor, reduced in-stent stenosis in the rat aorta, suggesting that carbon monoxide, a by-product of heme degradation, might contribute to the protective effect of hemin.
Conclusion:
These results suggest that HO-1 is important in limiting in-stent stenosis and can be regarded as a new therapeutic target.
