Adenovirus-Mediated Heme Oxygenase-1 Gene Transfer Inhibits the Development of Atherosclerosis in Apolipoprotein E–Deficient Mice

Juan, Shu Hui; Lee, Tzong‐Shyuan; Tseng, Kuang-Wen; Liou, Jun‐Yang; Shyue, Song Kun; Wu, Kenneth K.; Chau, Lee‐Young

doi:10.1161/hc3801.095663

Cited by 298 publications

(212 citation statements)

References 29 publications

(32 reference statements)

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“…Induction of HO-1 by chemical inducers results in the reduction of atherosclerotic lesions in LDL-receptor knockout mice and prevents transplant arteriosclerosis in mouse cardiac allografts (Hancock et al, 1998;Ishikawa et al, 2001). Similarly, adenovirus-mediated transfer of HO-1 to arteries significantly attenuates the development of atherosclerosis in apoE null mice and graft arteriosclerosis in a rat model of chronic allogeneic aorta rejection (Juan et al, 2001;Bouche et al, 2002). In addition, upregulation of HO-1 by heme analogues or by retroviral gene delivery lowers blood pressure in spontaneously hypertensive rats (Levere et al, 1990;Johnson et al, 1995;Sabaawy et al, 2001) while the targeted overexpression of HO-1 in lungs protects against pulmonary vessel wall hypertrophy induced by hypoxia (Minamino et al, 2001).…”

Section: Ho-1 As a Therapeutic Target In Vascular Diseasementioning

confidence: 98%

Heme oxygenase‐1 in growth control and its clinical application to vascular disease

Durante

2003

Journal Cellular Physiology

143

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Heme oxygenase-1 (HO-1) catalyzes the degradation of heme to carbon monoxide (CO), iron, and biliverdin. Biliverdin is subsequently metabolized to bilirubin by the enzyme biliverdin reductase. Although interest in HO-1 originally centered on its heme-degrading function, recent findings indicate that HO-1 exerts other biologically important actions. Emerging evidence suggests that HO-1 plays a critical role in growth regulation. Deletion of the HO-1 gene or inhibition of HO-1 activity results in growth retardation and impaired fetal development, whereas HO-1 overexpression increases body size. Although the mechanisms responsible for the growth promoting properties of HO-1 are not well established, HO-1 can indirectly influence growth by regulating the synthesis of growth factors and by modulating the delivery of oxygen or nutrients to specific target tissues. In addition, HO-1 exerts important effects on critical determinants of tissue size, including cell proliferation, apoptosis, and hypertrophy. However, the actions of HO-1 are highly variable and may reflect a role for HO-1 in maintaining tissue homeostasis. Considerable evidence supports a crucial role for HO-1 in blocking the growth of vascular smooth muscle cells (SMCs). This antiproliferative effect of HO-1 is mediated primarily via the release of CO, which inhibits vascular SMC growth via multiple pathways. Pharmacologic or genetic approaches targeting HO-1 or CO to the blood vessel wall may represent a promising, novel therapeutic approach in treating vascular proliferative disorders.

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Section: Ho-1 As a Therapeutic Target In Vascular Diseasementioning

confidence: 98%

Heme oxygenase‐1 in growth control and its clinical application to vascular disease

Durante

2003

Journal Cellular Physiology

143

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“…Recombinant adenovirus containing human HO-1 (Adv-HO-1) gene was prepared as described previously [4].…”

Section: Preparation Of Recombinant Adenovirusmentioning

confidence: 99%

“…Fifty lg of proteins was electrophoresed on 10% SDS-polyacrylamide gel and the transblotted onto the Immobilon TM -P membrane (Millipore). Western blot analysis was carried out as describe previously [4].…”

Section: Western Blot Analysismentioning

confidence: 99%

“…Over the past few years, numerous studies have supported the vital role of HO-1 in protecting vascular functions. Overexpression of HO-1 in arterial walls has been shown to reduce lesion formation and intimal hyperplasia subsequent to vascular injury in animals [2][3][4][5]. Several mechanisms were considered to participate in the vasoprotection conferred by HO-1.…”

Section: Introductionmentioning

confidence: 99%

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Carbon Monoxide-Induced Early Thrombolysis Contributes to Heme Oxygenase-1-Mediated Inhibition of Neointimal Growth after Vascular Injury in Hypercholesterolemic Mice

et al. 2006

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Arterial thrombosis is a critical event in the pathogenesis of lesion development. In this study, we evaluated the effect of heme oxygenase-1 (HO-1), a stress-inducible enzyme with vasoprotective functions, on arterial thrombosis following vascular mechanical injury. The carotid arteries of apoE-deficient mice were subjected to angioplasty with a modified beaded-needle. Arterial thrombosis occurred at 12 h after injury. Treatment of the injured vessels with an adenovirus bearing HO-1 gene (Adv-HO-1) (1Â 10 8 pfu), but not saline or empty adenovirus (Adv), immediately after angioplasty resulted in earlier thrombolysis and restoration of blood flow detected at 24 h. Immunohistochemistry revealed that the arterial plasminogen activator inhibitor-1 (PAI-1) expression was markedly reduced in Adv-HO-1-treated injured arteries as compared to control counterparts. The thrombolytic effect was also observed by exposing animals with existing arterial thrombosis to carbon monoxide (CO) (250 ppm, 2 h), a byproduct derived from heme degradation by HO-1. In parallel with less fibrin(ogen) deposition, the macrophage infiltration, monocyte chemoattractant protein-1 expression and neointimal formation assessed at 2 weeks after angioplasty were substantially reduced in injured arteries treated with Adv-HO-1. These results support a role of early thrombolysis induced by CO in HO-1-mediated protection against intimal hyperplasia after vascular injury.

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“…In the progress of atherosclerosis, under certain circumstances when some of the critical antioxidant enzymes including glutathione and superoxide dismutase (SOD) were reduced and the production of NO in endothelial cells was diminished, the activation of HO/CO pathway will build up an alternative important defense against oxidative insult. Recently, Juan et al [34] reported that adenovirus-mediated HO-1 gene transfer could inhibit the development of atherosclerosis in apoE-deficient mice. We here found that the over-expression of hHO-1 in the transfected VSMC could directly and significantly inhibit VSMC proliferation.…”

Section: Increase Of Cellular Cgmp and Decrease Of Mapk Phosphorylationmentioning

confidence: 99%

Overexpression of heme oxygenase-1 protects smooth muscle cells against oxidative injury and inhibits cell proliferation

Zhang

Chen

et al. 2002

Cell Res

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To investigate whether the expression of exogenous heme oxygenase-1 (HO-1) gene within vascular smooth muscle cells (VSMC) could protect the cells from free radical attack and inhibit cell proliferation, we established an in vitro transfection of human HO-1 gene into rat VSMC mediated by a retroviral vector. The results showed that the profound expression of HO-1 protein as well as HO activity was 1.8-and 2.0-fold increased respectively in the transfected cells compared to the non-transfected ones. The treatment of VSMC with different concentrations of H 2 O 2 led to the remarkable cell damage as indicated by survival rate and LDH leakage. However, the resistance of the HO-1 transfected VSMC against H 2 O 2 was significantly raised. This protective effect was dramatically diminished when the transfected VSMC were pretreated with ZnPP-IX, a specific inhibitor of HO, for 24 h. In addition, we found that the growth potential of the transfected cells was significantly inhibited directly by increased activity of HO-1, and this effect might be related to decreased phosphorylation of MAPK. These results suggest that the overexpression of introduced hHO-1 is potentially able to reduce the risk factors of atherosclerosis, partially due to its cellular protection against oxidative injury and to its inhibitory effect on cellular proliferation.

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Adenovirus-Mediated Heme Oxygenase-1 Gene Transfer Inhibits the Development of Atherosclerosis in Apolipoprotein E–Deficient Mice

Cited by 298 publications

References 29 publications

Heme oxygenase‐1 in growth control and its clinical application to vascular disease

Heme oxygenase‐1 in growth control and its clinical application to vascular disease

Carbon Monoxide-Induced Early Thrombolysis Contributes to Heme Oxygenase-1-Mediated Inhibition of Neointimal Growth after Vascular Injury in Hypercholesterolemic Mice

Overexpression of heme oxygenase-1 protects smooth muscle cells against oxidative injury and inhibits cell proliferation

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