Development of Angiotensin II-induced Abdominal Aortic Aneurysms Is Independent of Catalase in Mice

Uchida, Haruhito A.; Sugiyama, Hiroshi; Takiue, Keiichi; Kobayashi, Yôko; Inoué, Takao; Makino, Hírofumi

doi:10.1097/fjc.0b013e3182317196

Cited by 9 publications

(7 citation statements)

References 46 publications

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“…23 On the other hand, Uchida et al showed that catalase deficiency had no effect on angiotensin II-induced aortic aneurysms in mice. 24 In the present work, using the CaCl 2 model, we show that catalase expression and activity was substantially decreased early after vascular injury. Reconstitution of catalase activity either via pharmacologic administration or genetic tissue-specific over-expression in the VSMC had a profound protective effect against vascular wall damage and AAA formation.…”

Section: Discussionsupporting

confidence: 56%

“…Reconstitution of catalase activity either via pharmacologic administration or genetic tissue-specific over-expression in the VSMC had a profound protective effect against vascular wall damage and AAA formation. Of note, as opposed to angiotensin II infusion, which raised catalase activity, 24 vascular injury with CaCl 2 decreased aortic catalase activity. The differential response highlights the inherent differences in the mechanism of aneurysm induction between the 2 models.…”

Section: Discussionmentioning

confidence: 88%

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Overexpression of Catalase in Vascular Smooth Muscle Cells Prevents the Formation of Abdominal Aortic Aneurysms

Parastatidis

Weiss

Joseph

et al. 2013

ATVB

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Objective Elevated levels of oxidative stress have been reported in abdominal aortic aneurysms (AAA), but which reactive oxygen species (ROS) promotes the development of AAA remains unclear. Here we investigate the effect of the hydrogen peroxide (H2O2) degrading enzyme catalase on the formation of AAA. Approach and Results AAA were induced with the application of calcium chloride (CaCl2) on mouse infrarenal aortas. The administration of PEG-catalase, but not saline, attenuated the loss of tunica media and protected against AAA formation (0.91±0.1 mm vs. 0.76±0.09 mm). Similarly, in a transgenic mouse model, catalase over-expression in the vascular smooth muscle cells (VSMC) preserved the thickness of tunica media and inhibited aortic dilatation by 50% (0.85±0.14 mm vs. 0.57±0.08 mm). Further studies showed that injury with CaCl2 decreased catalase expression and activity in the aortic wall. Pharmacologic administration or genetic over-expression of catalase restored catalase activity and subsequently decreased matrix metalloproteinase activity. In addition, a profound reduction in inflammatory markers and VSMC apoptosis was evident in aortas of catalase over-expressing mice. Interestingly, as opposed to infusion of PEG-catalase, chronic over-expression of catalase in VSMC did not alter the total aortic H2O2 levels. Conclusions The data suggest that a reduction in aortic wall catalase activity can predispose to AAA formation. Restoration of catalase activity in the vascular wall enhances aortic VSMC survival and prevents AAA formation primarily through modulation of matrix metalloproteinase activity.

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Section: Discussionsupporting

confidence: 56%

Section: Discussionmentioning

confidence: 88%

Overexpression of Catalase in Vascular Smooth Muscle Cells Prevents the Formation of Abdominal Aortic Aneurysms

Parastatidis

Weiss

Joseph

et al. 2013

ATVB

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“…The catalase activity in each kidney was determined by an ELISA using a catalase assay kit [21]. All procedures were performed according to the manufacturer's instructions.…”

Section: Methodsmentioning

confidence: 99%

Acatalasemic mice are mildly susceptible to adriamycin nephropathy and exhibit increased albuminuria and glomerulosclerosis

et al. 2012

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BackgroundCatalase is an important antioxidant enzyme that regulates the level of intracellular hydrogen peroxide and hydroxyl radicals. The effects of catalase deficiency on albuminuria and progressive glomerulosclerosis have not yet been fully elucidated. The adriamycin (ADR) nephropathy model is considered to be an experimental model of focal segmental glomerulosclerosis. A functional catalase deficiency was hypothesized to exacerbate albuminuria and the progression of glomerulosclerosis in this model.MethodsADR was intravenously administered to both homozygous acatalasemic mutant mice (C3H/AnLCsbCsb) and control wild-type mice (C3H/AnLCsaCsa). The functional and morphological alterations of the kidneys, including albuminuria, renal function, podocytic, glomerular and tubulointerstitial injuries, and the activities of catalase were then compared between the two groups up to 8 weeks after disease induction. Moreover, the presence of a mutation of the toll-like receptor 4 (tlr4) gene, which was previously reported in the C3H/HeJ strain, was investigated in both groups.ResultsThe ADR-treated mice developed significant albuminuria and glomerulosclerosis, and the degree of these conditions in the ADR-treated acatalasemic mice was higher than that in the wild-type mice. ADR induced progressive renal fibrosis, renal atrophy and lipid peroxide accumulation only in the acatalasemic mice. In addition, the level of catalase activity was significantly lower in the kidneys of the acatalasemic mice than in the wild-type mice during the experimental period. The catalase activity increased after ADR injection in wild-type mice, but the acatalasemic mice did not have the ability to increase their catalase activity under oxidative stress. The C3H/AnL strain was found to be negative for the tlr4 gene mutation.ConclusionsThese data indicate that catalase deficiency plays an important role in the progression of renal injury in the ADR nephropathy model.

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“…Recent reports demonstrated that Ang II infusion promoted ascending aortic aneurysms and abdominal aortic aneurysms in apolipoprotein E−/− (ApoE−/−) and low-density lipoprotein receptor−/− (LDLR−/−) knockout mice [12][13][14][15]. Losartan reduced the aortic growth rate and prevented progressive aortic wall architecture deterioration in Marfan syndrome mice [16], whereas it attenuated aortic root dilation in Marfan syndrome patients [17].…”

Section: Introductionmentioning

confidence: 99%

Angiotensin II induces an increase in MMP-2 expression in idiopathic ascending aortic aneurysm via AT1 receptor and JNK pathway

Wang

Chang

Qian

et al. 2015

ABBS

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The cellular and molecular mechanisms responsible for human idiopathic ascending aortic aneurysm (IAAA) remain unknown. Matrix metalloproteinase-2 (MMP-2) is a key enzyme for the degradation of extracellular matrix in aneurysmal walls. The aim of this study was to elucidate the role of the angiotensin II (Ang II) pathway in MMP-2 induction in IAAA aortic walls. Quantitative polymerase chain reaction and western blot analysis were used to compare the MMP-2 mRNA and protein levels in ascending aortic specimens with those in IAAA patients (n = 10) and heart transplant donors (n = 5) without any aortopathy. It was found that MMP-2 expression was significantly increased, which was associated with elastic lamellae disruption in IAAA walls. Additionally, the expression levels of angiotensinogen (AGT) and Ang II in the ascending aortic tissues from individuals with and without IAAAs were detected by western blot analysis and radioimmunoassay, respectively. The results demonstrated that the expressions of AGT and Ang II protein were significantly increased in the ascending aortic tissues of IAAA patients. Furthermore, whether Ang II induces MMP-2 expression was investigated using human IAAA walls ex vivo culture. It was found that exogenous Ang II increased the MMP-2 expression in a dose-dependent manner, which was completely inhibited by the Ang II type 1 receptor (AT1R) inhibitor candesartan and was mediated by c-Jun N-terminal kinase (JNK) activation. Taken together, these results indicate that Ang II can induce an increase of MMP-2 expression via AT1R and JNK in ex vivo cultured IAAA aortic walls, and suggest that angiotensin receptor blocker (ARB) drugs and JNK inhibitors have the potential in the prevention or treatment of IAAAs.

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Development of Angiotensin II-induced Abdominal Aortic Aneurysms Is Independent of Catalase in Mice

Cited by 9 publications

References 46 publications

Overexpression of Catalase in Vascular Smooth Muscle Cells Prevents the Formation of Abdominal Aortic Aneurysms

Overexpression of Catalase in Vascular Smooth Muscle Cells Prevents the Formation of Abdominal Aortic Aneurysms

Acatalasemic mice are mildly susceptible to adriamycin nephropathy and exhibit increased albuminuria and glomerulosclerosis

Angiotensin II induces an increase in MMP-2 expression in idiopathic ascending aortic aneurysm via AT1 receptor and JNK pathway

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