Differential effects of everolimus and cyclosporine A on intimal alpha-actin-positive cell dynamics of carotid allografts in mice.

Background: We recently demonstrated that donor medial cells are replaced by smooth muscle alpha-actin (SMA)-expressing host cells in murine carotid allografts. In this study, we investigated neointimal cell dynamics including effects of cyclosporine A (CsA) and everolimus (SDZ RAD, Certican). To obtain a functional readout, we measured the effects of these treatments on cardiac allografts.

Dynamics of medial smooth muscle changes after carotid artery transplantation in transgenic mice expressing green fluorescent protein.

Background: Recent observations have demonstrated the importance of host cells in neointima formation after transplantation. Because little is known regarding the dynamics of host-derived cells in the graft media, we investigated this question in a mouse carotid artery transplantation model.

Methods: C57BL/6 carotid arteries were orthotopically transplanted into BALB/c mice ubiquitously expressing enhanced green fluorescent protein.

Differential effect of cyclosporine A and SDZ RAD on neointima formation of carotid allografts in apolipoprotein E-deficient mice.

Background: Apolipoprotein E-deficient (apoE-/-) mice spontaneously develop hypercholesterolemia and atherosclerotic lesions. This may be an appropriate background for the development of graft vessel disease. The authors therefore investigated the effects of cyclosporine A (CsA) and SDZ RAD (RAD, everolimus, Certican) on neointima formation of carotid allografts in apoE-/- mice.

Efficacy of mycophenolate sodium as monotherapy and in combination with FTY720 in a DA-to-Lewis-rat heart-transplantation model.

Background: Mycophenolate sodium (MPS), which is in clinical development as an enteric-coated tablet (Myfortic), has not yet been characterized as a combination partner of FTY720. We therefore report here the effects of MPS and FTY720 mono and combination therapy in a rat heart allograft model.

Methods: Heterotopic heart allotransplantation was performed in the DA-to-Lewis-strain combinations.

Efficacy of SDZ RAD compared with CsA monotherapyand combined Rad/FTY720 treatment in a murine cardiac allotransplantation model.

Objective: The macrolide immunosuppressant RAD and the immunomodulator FTY720 have distinct mechanisms ofaction. We investigated the efficacy of RAD (everolimus, certican) alone or in combination with FTY720 on graft survival (GS)and histology in comparison with CsA, using mouse strains with strong MHC disparity.

Methods: Heterotopic cardiac grafting was performed using the C57B1/6 to C3H strain combination.