Zoledronate attenuates angiotensin II-induced abdominal aortic aneurysm through inactivation of Rho/ROCK-dependent JNK and NF-κB pathway

Tsai, Shih‐Hung; Huang, Po‐Hsun; Peng, Yi‐Jen; Chang, Wei‐Chou; Tsai, Hung-Chin; Leu, Hsin‐Bang; Chen, Jaw-Wen; Lin, Shing‐Jong

doi:10.1093/cvr/cvt230

Cited by 57 publications

(46 citation statements)

References 42 publications

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“…A recent study showed that inhibitor of nuclear factor kappa-B kinase epsilon (IKKe) is related to vascular inflammation, which accounts for its important role in the atherosclerosis, and it also has a potential relationship with the hypertension [13]. The role of IKKe in the development of atherosclerosis was further verified in our previous investigation, and recent studies have confirmed that atherosclerosis is a risk factor for AA [1,6,13].…”

Section: Introductionsupporting

confidence: 66%

“…The role of IKKe in the development of atherosclerosis was further verified in our previous investigation, and recent studies have confirmed that atherosclerosis is a risk factor for AA [1,6,13]. Matrix metalloproteinase-2 (MMP-2), a downstream of IKKe, is widespread and responsible for extracellular collagen degradation and remodelling [8].…”

Section: Introductionsupporting

confidence: 63%

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The expression of inhibitor of nuclear factor kappa-B kinase epsilon (IKKe) in human aortic aneurysm

Zhang

Wang²,

Chen³

et al. 2017

Folia Morphol

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Section: Introductionsupporting

confidence: 66%

Section: Introductionsupporting

confidence: 63%

The expression of inhibitor of nuclear factor kappa-B kinase epsilon (IKKe) in human aortic aneurysm

Zhang

Wang²,

Chen³

et al. 2017

Folia Morphol

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“…However, in contrast to Tsai et al, we found no suppression of AAA ( Figure XX in the online-only Data Supplement). 4,33,34 These differing results may be because of the amount of ZA binding to CaPO 4 . We also speculate that the absence of a bisphosphonate effect is related to the lack of overt arterial calcification in aneurysms in this model.…”

Section: Discussionmentioning

confidence: 99%

“…Nistala et al also reported negative results for bisphosphonate on aneurysm progression in Marfan syndrome using Fbn1 (mgR/ mgR) mice. 33,35 Because Fbn1 mice more closely mimic connective tissue disorders, such as Marfan syndrome, we think that the underlying mechanism in this model differs from the pathophysiology of the traditional AAA model.…”

Section: Discussionmentioning

confidence: 99%

Osteoclastogenic Differentiation of Macrophages in the Development of Abdominal Aortic Aneurysms

Takei

Tanaka

Kent

et al. 2016

ATVB

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Objective-Arterial calcification is common and contributes to the pathogenesis of occlusive vascular disease. Similar to the dynamics of bone, it is a tightly controlled process that maintains a balance between osteogenesis and osteolysis. However, whether calcium homeostasis plays a role in the development of aneurysms has not been explored. We hypothesized that macrophages differentiate into osteoclasts in aneurysmal arteries and that protease byproducts contribute to aneurysm pathophysiology. Approach and Results-We performed histological and immunohistochemical analyses and showed that macrophages positive for several osteoclast markers, including tartrate acid phosphatase, occur in great numbers in the human aneurysmal aorta, but very few occur in the human stenotic aorta and none in the nondiseased human aorta. Moreover, in situ zymography showed elevated protease activity in these cells compared with undifferentiated macrophages. Tumor necrosis factor-α and calcium phosphate stimulated this osteoclastogenic differentiation process through nuclear factor-κB, mitogen-activated protein kinases, and intracellular calcium signaling but not the receptor activator of the nuclear factor-κB ligand. Inhibition of osteoclastogenic differentiation by bisphosphonate inhibits aneurysm development in a mouse model. Conclusions-These

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“…It is generally reported that phosphorylation of ERK and JNK is increased in AngII-induced AAA tissues, whereas p38 phosphorylation is not changed in AAA walls. 31 However, it is reported that phosphorylation of ERK and JNK vary by the region of aorta. 32 Because we used whole aortic tissues to examine protein expression, this apparent discrepancy may have occurred because of these concerns.…”

Section: Sawada Et Al Iron and Abdominal Aortic Aneurysm 1513mentioning

confidence: 99%

Aortic Iron Overload With Oxidative Stress and Inflammation in Human and Murine Abdominal Aortic Aneurysm

Sawada

Hao

Naito

et al. 2015

ATVB

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A bdominal aortic aneurysm (AAA) is a common vascular disease, which occurs in ≈4% to 8% of men aged 65 to 80 years.1 Aortic rupture is the most feared clinical consequence of AAA progression, resulting in mortality in ≈90% of cases. [2][3][4] Because AAA usually progresses without symptoms, AAA is often discovered in advanced stage. At present, surgical aortic replacement and endovascular stent graft repair are performed as standard definitive therapies for AAA. However, there is no effective medical therapy to prevent aortic rupture in AAA. Although several studies have reported the pathophysiology of AAA, the mechanisms of AAA formation are largely unknown. Therefore, it is necessary to investigate the molecular pathophysiology of AAA to find noninvasive strategies for the prevention of AAA.Iron is an essential element for maintaining physiological function. However, excess iron causes tissue damage by oxidative stress via the Fenton/Haber-Weiss reaction. 5Therefore, iron is involved in the pathophysiology of several diseases including cardiovascular diseases. In fact, we have previously shown that iron accumulation and superoxide production are observed in the renal tubules of a rat model of chronic kidney disease.6 Lee et al 7 have shown that iron accumulation is observed in the atherosclerotic lesions of apolipoprotein E knockout mice. Most recently, Martinez-Pinna et al 8 have demonstrated that iron is deposited in human AAA walls. Meanwhile, we have also reported that dietary iron restriction (IR) prevents the development of hypertension and proteinuria with inhibition of oxidative stress and inflammation in Dahl salt-sensitive hypertensive rats.9 Although oxidative stress and inflammation are well known to be involved in the development of AAA formation, it has not been investigated whether iron is associated with the pathophysiology of AAA through © 2015 American Heart Association, Inc. Objective-Although iron is an essential element for maintaining physiological function, excess iron leads to tissue damage caused by oxidative stress and inflammation. Oxidative stress and inflammation play critical roles for the development of abdominal aortic aneurysm (AAA). However, it has not been investigated whether iron plays a role in AAA formation through oxidative stress and inflammation. We, therefore, examined whether iron is involved in the pathophysiology of AAA formation using human AAA walls and murine AAA models. Approach and Results-Human aortic walls were collected from 53 patients who underwent cardiovascular surgery (non-AAA=34; AAA=19). Murine AAA was induced by infusion of angiotensin II to apolipoprotein E knockout mice. Iron was accumulated in human and murine AAA walls compared with non-AAA walls. Immunohistochemistry showed that both 8-hydroxy-2′-deoxyguanosine and CD68-positive areas were increased in AAA walls compared with non-AAA walls. The extent of iron accumulated area positively correlated with that of 8-hydroxy-2′-deoxyguanosine expression area and macrophage infiltration area in huma...

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Zoledronate attenuates angiotensin II-induced abdominal aortic aneurysm through inactivation of Rho/ROCK-dependent JNK and NF-κB pathway

Abstract: Zoledronate-attenuated Ang II induced AAA formation by suppression of MMP-2 activity and suppressed vascular inflammation and Ang II-induced Rho/ROCK activities.

Cited by 57 publications

References 42 publications

The expression of inhibitor of nuclear factor kappa-B kinase epsilon (IKKe) in human aortic aneurysm

The expression of inhibitor of nuclear factor kappa-B kinase epsilon (IKKe) in human aortic aneurysm

Osteoclastogenic Differentiation of Macrophages in the Development of Abdominal Aortic Aneurysms

Aortic Iron Overload With Oxidative Stress and Inflammation in Human and Murine Abdominal Aortic Aneurysm

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