Atorvastatin attenuates transplant-associated coronary arteriosclerosis in a murine model of cardiac transplantation.
Accelerated coronary arteriosclerosis remains a major problem for the long-term survival of cardiac transplant recipients. However, the pathogenesis of transplant vasculopathy is poorly understood and there is no effective therapy. HMG-CoA reductase inhibitors, or statins, are widely prescribed to lower plasma cholesterol level. Accumulating evidence indicates that statins have various effects on vascular cells which are independent of their lipid-lowering effect. We investigated whether orally administered atorvastatin, one of the most potent statins, inhibits the development of intima hyperplasia in a mouse model of cardiac transplantation. Cardiac allografts from DBA mice were transplanted heterotopically into B10.D2 mice. Mice were administered either vehicle or atorvastatin everyday by gavage. Morphometrical analysis revealed that atorvastatin significantly reduced the development of coronary arteriosclerosis on the cardiac allografts harvested at one month. Immunohistochemical analysis revealed that atorvastatin attenuated infiltration of inflammatory cells with reduced expression of TGF-beta and adhesion molecules. These results suggest that atorvastatin may be effective in preventing transplant-associated arteriosclerosis along with other immunosuppressive agents.
Shirakawa
Ibuki
I
Department of Cardiovascular Medicine, University of Tokyo, Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Sata
Masataka
M
Saiura
Akio
A
Kaneda
Yukari
Y
Yashiro
Hisako
H
Hirata
Yasunobu
Y
Makuuchi
Masatoshi
M
Nagai
Ryozo
R
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000069059:Atorvastatin; D003324:Coronary Artery Disease / Q000209:etiology / Q000517:prevention & control*; D005786:Gene Expression Regulation; D016027:Heart Transplantation / Q000009:adverse effects*; D006538:Heptanoic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D006965:Hyperplasia / Q000517:prevention & control; D007150:Immunohistochemistry; D051379:Mice; D008811:Mice, Inbred DBA; D011758:Pyrroles / Q000494:pharmacology* / Q000627:therapeutic use; D016212:Transforming Growth Factor beta / Q000187:drug effects / Q000378:metabolism; D017539:Tunica Intima / Q000187:drug effects; D014652:Vascular Diseases / Q000209:etiology / Q000517:prevention & control*
D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D011758:Pyrroles; D016212:Transforming Growth Factor beta; D000069059:Atorvastatin