| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 4260534 | Transplantation Proceedings | 2006 | 4 Pages |
Chronic rejection in transplanted hearts or cardiac allograft vasculopathy (CAV) is the leading cause of late death among heart transplant recipients. We hypothesized that induction of HO-1 by D4-F, an apoA-I mimetic peptide with potent antiinflammatory/antioxidant properties, attenuated CAV.We utilized a previously characterized murine model of CAV. B6.C-H2bml2 hearts were heterotopically transplanted into C57BL/6 mice. In the control group, recipient mice were treated with 20 μg of saline daily. In experimental group I, mice were treated daily with 20 μg of D4-F. In experimental group II, mice were treated daily with 20 μg of D4-F daily, plus CuPP, which does not have any effect on HO-1 activity. In experimental group III, recipient mice were treated with 20 μg of D4-F daily, plus SnPP, which is a competitive inhibitor of HO-1. Donor hearts were harvested on day 24 after transplantation.The donor hearts in the control group developed severe intimal lesions. In experimental group I, treatment with D4-F was associated with upregulation of HO-1 and a marked reduction in intimal lesions, which was consistent in experimental group II. In experimental group III, inhibition of HO-1 was associated with partial restoration of intimal lesions.Induction of HO-1 by an apoA-1 mimetic peptide was effective to control CAV. This class of antiinflammatory peptides, which show an ability to induce HO-1, provides a novel strategy for the treatment of CAV.
