Angiotensin II–accelerated atherosclerosis and aneurysm formation is attenuated in osteopontin-deficient mice

Bruemmer, Dennis; Collins, Alan R.; Noh, Grace; Wang, Wei; Territo, Mary; Arias-Magallona, Sarah; Fishbein, Michael C.; Blaschke, Florian; Kintscher, Ulrich; Graf, Kristof; Law, Ronald E.; Hsueh, Willa A.

doi:10.1172/jci18141

Cited by 171 publications

(167 citation statements)

References 59 publications

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“…These findings promoted us that the similar mechanism may exist in the development of aortic aneurysm. Bruemmer et al discovered that the development of AAA in the rats which had been knocked out gene of OPN was suppressed [15] . The findings of Nakashima et al revealed that treatment with NF-κB inhibitors could lead to the similar results [16] .…”

Section: Discussionmentioning

confidence: 99%

The elevated expression of osteopontin and NF-κB in human aortic aneurysms and its implication

Nie

Zhang

et al. 2011

J. Huazhong Univ. Sci. Technol. [Med. Sci.]

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The expression and significance of osteopontin (OPN) and NF-κB in patients with thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA) were investigated. Thirteen TAA specimens, 20 AAA specimens and 6 normal aortic specimens were collected. The expression of OPN, nuclear factor-κB P65 (NF-κB P65), urokinase plasminogen activator (uPA), matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) were detected by using immunohistochemistry and Western blotting was employed to determine the expression of OPN and NF-κB P65. Immunohistochemical results showed that the expression of OPN, NF-κB P65, uPA, MMP-2 and MMP-9 was positive in all TAA and AAA specimens and negative in normal specimens, with the difference being statistically significant (P<0.05). There was no difference in the expression between TAA and AAA specimens (P>0.05). Correlation analysis revealed that there existed a positive correlation between the expression of OPN and that of NF-κB P65, uPA, MMP-2 and MMP-9 and between the expression of NF-κB P65 and that of uPA, MMP-2, MMP-9 (P<0.05). Western blotting demonstrated that OPN and NF-κB P65 were positive in AAA and TAA specimens, and negative in normal specimens with the differences being statistically significant (P<0.05). There were no statistically significant differences in the expression of OPN and NF-κB P65 between AAA and TAA specimens (P>0.05). It was concluded that OPN and NF-κB P65 were involved in the pathogenesis of TAA and AAA. OPN can up-regulate the expression of MMP and uPA via NF-κB signaling pathway thereby accelerating the degradation of extracellular matrix and playing an important role in the pathogenesis and development of TAA and AAA.

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Section: Discussionmentioning

confidence: 99%

The elevated expression of osteopontin and NF-κB in human aortic aneurysms and its implication

Nie

Zhang

et al. 2011

J. Huazhong Univ. Sci. Technol. [Med. Sci.]

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“…193 Key mechanisms include VSMC senescence, 194 oxidative stress, 12,195 increased local production of proinflammatory cytokines, and increased MMPs activities that degrade the extracellular matrix. 196 Chronic AngII infusion into apolipoprotein E knockout mice promotes aortic aneurysm formation. 197,198 In animal models of aortic aneurysm, genetic and pharmacological inhibition of ROS production 199,200 and MMPs 201,202 suppressed the development of aneurysm.…”

Section: Rho-kinase In Vascular Diseasesmentioning

confidence: 99%

RhoA/Rho-Kinase in the Cardiovascular System

Shimokawa

Sunamura

Satoh

2016

Circulation Research

369

235

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Twenty years ago, Rho-kinase was identified as an important downstream effector of the small GTP-binding protein, RhoA. Thereafter, a series of studies demonstrated the important roles of Rho-kinase in the cardiovascular system. The RhoA/Rho-kinase pathway is now widely known to play important roles in many cellular functions, including contraction, motility, proliferation, and apoptosis, and its excessive activity induces oxidative stress and promotes the development of cardiovascular diseases. Furthermore, the important role of Rho-kinase has been demonstrated in the pathogenesis of vasospasm, arteriosclerosis, ischemia/reperfusion injury, hypertension, pulmonary hypertension, and heart failure. Cyclophilin A is secreted by vascular smooth muscle cells and inflammatory cells and activated platelets in a Rho-kinase–dependent manner, playing important roles in a wide range of cardiovascular diseases. Thus, the RhoA/Rho-kinase pathway plays crucial roles under both physiological and pathological conditions and is an important therapeutic target in cardiovascular medicine. Recently, functional differences between ROCK1 and ROCK2 have been reported in vitro. ROCK1 is specifically cleaved by caspase-3, whereas granzyme B cleaves ROCK2. However, limited information is available on the functional differences and interactions between ROCK1 and ROCK2 in the cardiovascular system in vivo. Herein, we will review the recent advances about the importance of RhoA/Rho-kinase in the cardiovascular system.

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“…Recently, it was reported that deficiency of osteopontin decreased Ang II-induced AAA formation in apolipoprotein E -/-mice [25]. Osteopontin was originally identified as a molecule that mediates osteoclast adhesion to mineralized matrix.…”

Section: Modes Of Inhibiting Angiotensin Ii-induced Abdominal Aortic mentioning

confidence: 99%

Angiotensin II and abdominal aortic aneurysms

Daugherty

Cassis

2004

Current Science Inc

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Abdominal aortic aneurysms (AAAs) have devastating effects on the morbidity and mortality of a large portion of the elderly population. Current therapeutic options for AAAs are limited to surgical approaches, because there are no proven pharmacologic treatments. Recently, there is evolving evidence that angiotensin II (Ang II) participates in the initiation and propagation of AAAs. Animal studies have consistently demonstrated the ability of Ang II to promote the formation of AAAs, although the mechanisms of this effect have not been defined. Further definition of the role of the renin-angiotensin system in AAA formation and progression will identify potential therapeutic strategies for treatment of this disease.

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Angiotensin II–accelerated atherosclerosis and aneurysm formation is attenuated in osteopontin-deficient mice

Cited by 171 publications

References 59 publications

The elevated expression of osteopontin and NF-κB in human aortic aneurysms and its implication

The elevated expression of osteopontin and NF-κB in human aortic aneurysms and its implication

RhoA/Rho-Kinase in the Cardiovascular System

Angiotensin II and abdominal aortic aneurysms

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