BACKGROUND AND PURPOSE: Previous studies demonstrated that intraplaque haemorrhage increased the contents of cholesterol and oxidants in atherosclerotic plaques. The present study was aimed to test the hypothesis that enhanced expression of haem oxygenase-1 (HO-1) may stabilize vulnerable plaques. EXPERIMENTAL APPROACH: Intravascular ultrasound (IVUS) was performed to identify three similar abdominal aortic plaques in each of 58 fat-fed New Zealand rabbits after aortic balloon injury. With the guidance of IVUS, 50 microL autologous erythrocytes (RBC) or normal saline (NS) were injected from adventitia into two of the pre-selected plaques, respectively, whereas the third plaque served as a blank control. All rabbits were randomly divided into two groups, receiving intraperitoneal injection of haemin and saline respectively. KEY RESULTS: Compared with NS or control plaques, RBC plaques had more macrophage infiltration and lipid content, thinner plaque fibrous cap, and higher expression of inflammatory factors and incidence of plaque rupture. RBC plaques in the haemin group had about a 50% lower incidence of plaque rupture than those in the control group. CONCLUSIONS AND IMPLICATIONS: Haem oxygenase-1 may eliminate haem or other oxidants, exert unexpected anti-oxidative and anti-inflammatory effects and serve as a promising approach to the direct inhibition of erythrocyte-induced plaque instability.
BACKGROUND AND PURPOSE: Previous studies demonstrated that intraplaque haemorrhage increased the contents of cholesterol and oxidants in atherosclerotic plaques. The present study was aimed to test the hypothesis that enhanced expression of haem oxygenase-1 (HO-1) may stabilize vulnerable plaques. EXPERIMENTAL APPROACH: Intravascular ultrasound (IVUS) was performed to identify three similar abdominal aortic plaques in each of 58 fat-fed New Zealand rabbits after aortic balloon injury. With the guidance of IVUS, 50 microL autologous erythrocytes (RBC) or normal saline (NS) were injected from adventitia into two of the pre-selected plaques, respectively, whereas the third plaque served as a blank control. All rabbits were randomly divided into two groups, receiving intraperitoneal injection of haemin and saline respectively. KEY RESULTS: Compared with NS or control plaques, RBC plaques had more macrophage infiltration and lipid content, thinner plaque fibrous cap, and higher expression of inflammatory factors and incidence of plaque rupture. RBC plaques in the haemin group had about a 50% lower incidence of plaque rupture than those in the control group. CONCLUSIONS AND IMPLICATIONS: Haem oxygenase-1 may eliminate haem or other oxidants, exert unexpected anti-oxidative and anti-inflammatory effects and serve as a promising approach to the direct inhibition of erythrocyte-induced plaque instability.
Authors: M Torzewski; M Klouche; J Hock; M Messner; B Dorweiler; J Torzewski; H E Gabbert; S Bhakdi Journal: Arterioscler Thromb Vasc Biol Date: 1998-03 Impact factor: 8.311
Authors: Shaw-Fang Yet; Matthew D Layne; Xiaoli Liu; Yen-Hsu Chen; Bonna Ith; Nicholas E S Sibinga; Mark A Perrella Journal: FASEB J Date: 2003-07-03 Impact factor: 5.191
Authors: Gerhard Krönke; Valery N Bochkov; Joakim Huber; Florian Gruber; Stefan Blüml; Alexander Fürnkranz; Alexandra Kadl; Bernd R Binder; Norbert Leitinger Journal: J Biol Chem Date: 2003-09-30 Impact factor: 5.157