标题：Heme oxygenase-1 inhibits progression and destabilization of vulnerable plaques in a rabbit model of atherosclerosis
作者：Li Tingting; Tian Hongbo; Zhao Yuxia; An Fengshuang; Zhang Lei; Zhang Jianning; Peng Jei; Zhang Yun; Guo Yuan
作者机构：[Guo Yuan] Shandong Univ, Dept Cardiol, Chinese Minist Educ,Qilu Hosp, Key Lab Cardiovasc Remodeling & Funct Res, Jinan 250012, Shandong, Peoples R Ch 更多
通讯作者地址：[Guo, Y]Shandong Univ, Dept Cardiol, Chinese Minist Educ,Qilu Hosp, Key Lab Cardiovasc Remodeling & Funct Res, 107 Wenhua W Rd, Jinan 250012, Shandong 更多
来源：EUROPEAN JOURNAL OF PHARMACOLOGY
关键词：Vulnerable plaque; Inflammation; Apoptosis; Nitric oxide; Heme oxygenase
摘要：Although heme oxygenase-1 (HO-1) has been implicated in protection against atherogenesis, its role in vulnerable plaques remains to be fully elucidated. This study was aimed to explore the effect of HO-1 on the progression and stabilization of vulnerable plaques and the possible mechanism. We established a vulnerable plaque model by local transfection with recombinant p53 adenovirus to plaques in rabbits fed a high-cholesterol diet. HO-1 activity was modulated by intraperitoneal injection of hemin or Sn-protoporphyrin IX (SnPP). HO-1 induction by hemin inhibited the progression of atherosclerotic lesions and changed the plaque morphology and composition into a more stable phenotype. In addition, hemin treatment is associated with a reduction in matrix metalloproteinase-9, interleukin-6 and tumor necrosis factor-alpha production, an increase in interleukin-10 level, as well as a decrease of TUNEL labeled apoptosis of smooth muscle cells in lesions. Compared with the control group, aortic nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) activity decreased markedly, whereas endothelial nitric oxide synthase (eNOS) activity increased significantly in the Hemin group. In contrast, inhibition of HO-1 by SnPP induced reversed effects and augmented plaque progression and vulnerability. After pharmacological triggering, the incidence of plaque disruption in SnPP group was significantly higher than that in control group (79% vs. 33%, P<0.05), while no plaque in Hemin group developed disruption (0% vs. 33%, P<0.05). These findings suggest that HO-1 induction could delay progression and enhance stability of atherosclerotic plaques, possibly through the attenuation of plaque inflammation and apoptosis, and the suppression of iNOS/NO production. (C) 2011 Elsevier B.V. All rights reserved.