scholarly journals Inducible Depletion of Calpain-2 Mitigates Abdominal Aortic Aneurysm in Mice

2021 ◽  
Author(s):  
Latha Muniappan ◽  
Michihiro Okuyama ◽  
Aida Javidan ◽  
Devi Thiagarajan ◽  
Weihua Jiang ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Smooth Muscle ◽  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Structural Integrity ◽  
Mesenchymal Cell ◽  
Ang Ii ◽  
Structural Protein ◽  
Abdominal Aortic ◽  
Calpain 2

Objective: Cytoskeletal structural proteins maintain cell structural integrity by bridging extracellular matrix with contractile filaments. During abdominal aortic aneurysm (AAA) development, (1) aortic medial degeneration is associated with loss of smooth muscle cell integrity and (2) fibrogenic mesenchymal cells mediate extracellular matrix remodeling. Calpains cleave cytoskeletal proteins that maintain cell structural integrity. Pharmacological inhibition of calpains exert beneficial effects on Ang II (angiotensin II)–induced AAAs in LDLR −/− (low-density receptor deficient) mice. Here, we evaluated the functional contribution of fibrogenic mesenchymal cells-derived calpain-2 on (1) cytoskeletal structural protein and extracellular matrix alterations and (2) AAA progression. Approach and Results: Calpain-2 protein and cytoskeletal protein (filamin and talin) fragmentation are significantly elevated in human and Ang II–induced AAAs in mice. To examine the relative contribution of calpain-2 in AAA development, calpain-2 floxed mice in an LDLr −/− background were bred to mice with a tamoxifen-inducible form of Cre under control of either the ubiquitous promoter, chicken β-actin, or fibrogenic mesenchymal cell-specific promoter, Col1α2. Ubiquitous or fibrogenic mesenchymal cell-specific depletion of calpain-2 in mice suppressed Ang II–induced AAAs, filamin/talin fragmentation, while promoting extracellular matrix protein, collagen in the aortas. Calpain-2 silencing in aortic smooth muscle cells or fibroblasts reduced Ang II–induced filamin fragmentation. In addition, silencing of filamin in aortic SMCs significantly reduced collagen protein. Furthermore, calpain-2 deficiency suppressed rupture of established Ang II–induced AAAs in mice. Conclusions: Our studies implicate that calpain-2 deficiency prevents (1) Ang II–induced cytoskeletal structural protein fragmentation and AAA development and (2) stabilize and suppress rupture of established AAAs in mice.

Abstract 25: Inducible Depletion of Calpain-2 Attenuates Angiotensin II-induced Cytoskeletal Structural Protein Destruction During Abdominal Aortic Aneurysm Development in Mice

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Latha Muniappan ◽  
Aida Javidan ◽  
Weihua Jiang ◽  
Jessica J Moorleghen ◽  
Anju Balakrishnan ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Angiotensin Ii ◽  
Aortic Aneurysm ◽  
Structural Integrity ◽  
Critical Role ◽  
Cysteine Proteases ◽  
Filamin A ◽  
Structural Protein ◽  
Abdominal Aortic ◽  
Calpain 2

Background and Objective: In abdominal aortic aneurysm (AAA) patients, structural integrity of the aortic wall is disrupted due to the dissociation of cytoskeletal structural proteins that bridge SMC contractile filaments with extracellular matrix by proteases. However, identity of functional proteases which target cytoskeletal structural linker proteins remain unknown. Recently, using the angiotensin II (AngII)-induced AAA model, we demonstrated that AngII significantly increased fragmentation of cytoskeletal structural protein, Filamin A, in AAAs. Further, using a pharmacological inhibitor and genetic deficient mice, we identified that calpain-2 (a class of calcium-activated, intracellular cysteine proteases) plays a critical role in AngII-induced AAA formation in mice. The purpose of this study was to determine the functional contribution of calpain-2 in AngII-induced cytoskeletal structural protein destruction during AAA development. Methods and Results: Calpain-2 floxed mice that were hemizygous for Cre-ERT2 in an LDLr -/- background were produced by breeding male Cre-ERT2 to female calpain-2 floxed mice. At 8 weeks of age, male Calp-2 x Cre-ERT2 (Cre+) and non-Cre littermates (Cre-) mice were injected with tamoxifen (25 mg/kg, i.p.) daily for 5 consecutive days. After 2 weeks, Western blot analyses showed a complete depletion of calpain-2 protein in the aorta from Cre+ mice compared to Cre- littermates. Male Cre+ and Cre- (N=12 each) mice were fed a Western diet and infused with saline or AngII (1,000 ng/kg/min) by osmotic minipumps for 2 weeks. AngII infusion significantly (P<0.05 vs saline) increased c-terminal fragmentation of cytoskeletal structural protein, talin and kinases such as integrin linked kinase-1 (ILK-1), and focal adhesion kinase in addition to filamin A. Inducible depletion of calpain-2 significantly (P<0.05; Cre+ vs Cre-) blunted AngII-induced fragmentation of talin, filamin A and ILK-1. Further siRNA mediated silencing of calpain-2 in aortic SMCs and fibroblasts significantly reduced AngII-induced fragmentation of filamin A and talin. Conclusion: These findings suggest that calpain-2 plays a critical role in AngII-induced cytoskeletal structural protein fragmentation during AAA development in mice.

scholarly journals LncRNA SENCR suppresses abdominal aortic aneurysm formation by inhibiting smooth muscle cells apoptosis and extracellular matrix degradation

2020 ◽  
Author(s):  
Zhou Cai ◽  
Jianhua Huang ◽  
Junxiao Yang ◽  
Baihong Pan ◽  
Wei Wang ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Smooth Muscle ◽  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Smooth Muscle Cells ◽  
Cell Apoptosis ◽  
Ang Ii ◽  
Matrix Degradation ◽  
Extracellular Matrix Degradation ◽  
Abdominal Aortic

Abdominal aortic aneurysm (AAA) is a progressive chronic dilatation of the abdominal aorta without effective medical treatment. This study aims to clarify the potential of long non-coding RNA SENCR as a treatment target in AAA. Angiotensin II (Ang-II) was used to establish AAA mouse model as well as a cell model based on the mouse aortic vascular smooth muscle cells (VSMCs). Reverse transcription quantitative PCR and western blot were performed to measure the expression of SENCR and proteins, respectively. Apoptotic rate in VSMCs was determined using Annexin V-FITC/PI double staining, and cell apoptosis in aortic tissues was determined by TUNEL staining. Hematoxylin and eosin and Elastica van Gieson staining were used for histological analysis of aortic tissues. SENCR was downregulated in AAA tissues and Ang-II-stimulated VSMCs. Overexpression of SENCR inhibited Ang-II-induced VSMC apoptosis, while inhibition of SENCR facilitated VSMC apoptosis. Moreover, overexpression of SENCR suppressed matrix metalloproteinase (MMP)-2 and MMP-9 expression and promoted tissue inhibitor of metalloproteinases 1 (TIMP-1) expression in Ang-II-induced VSMCs, while inhibition of SENCR expression led to the opposite results. In vivo, overexpressed SENCR improved the pathological change in aortic tissues and the damage in arterial wall elastic fibres induced by Ang-II, as well as it suppressed Ang-II-induced cell apoptosis and extracellular matrix degradation in aortic tissues. Overall, overexpression of SENCR inhibited AAA formation via suppressing VSMC apoptosis and extracellular matrix degradation. We provided a reliable evidence for SENCR acting as a potential target for AAA treatment.

scholarly journals Excessive EP4 Signaling in Smooth Muscle Cells Induces Abdominal Aortic Aneurysm by Amplifying Inflammation

2020 ◽  
Vol 40 (6) ◽  
pp. 1559-1573
Author(s):  
Taro Hiromi ◽  
Utako Yokoyama ◽  
Daisuke Kurotaki ◽  
Al Mamun ◽  
Ryo Ishiwata ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Macrophage Infiltration ◽  
Prostaglandin E ◽  
Ang Ii ◽  
Inflammatory Monocyte ◽  
Abdominal Aortic

Objective: Excessive prostaglandin E 2 production is a hallmark of abdominal aortic aneurysm (AAA). Enhanced expression of prostaglandin E 2 receptor EP4 (prostaglandin E receptor 4) in vascular smooth muscle cells (VSMCs) has been demonstrated in human AAAs. Although moderate expression of EP4 contributes to vascular homeostasis, the roles of excessive EP4 in vascular pathology remain uncertain. We aimed to investigate whether EP4 overexpression in VSMCs exacerbates AAAs. Approach and Results: We constructed mice with EP4 overexpressed selectively in VSMCs under an SM22α promoter (EP4-Tg). Most EP4-Tg mice died within 2 weeks of Ang II (angiotensin II) infusion due to AAA, while nontransgenic mice given Ang II displayed no overt phenotype. EP4-Tg developed much larger AAAs than nontransgenic mice after periaortic CaCl 2 application. In contrast, EP4 fl/+ ;SM22-Cre;ApoE −/ − and EP4 fl/+ ;SM22-Cre mice, which are EP4 heterozygous knockout in VSMCs, rarely exhibited AAA after Ang II or CaCl 2 treatment, respectively. In Ang II–infused EP4-Tg aorta, Ly6C hi inflammatory monocyte/macrophage infiltration and MMP-9 (matrix metalloprotease-9) activation were enhanced. An unbiased analysis revealed that EP4 stimulation positively regulated the genes binding cytokine receptors in VSMCs, in which IL (interleukin)-6 was the most strongly upregulated. In VSMCs of EP4-Tg and human AAAs, EP4 stimulation caused marked IL-6 production via TAK1 (transforming growth factor-β–activated kinase 1), NF-κB (nuclear factor-kappa B), JNK (c-Jun N-terminal kinase), and p38. Inhibition of IL-6 prevented Ang II–induced AAA formation in EP4-Tg. In addition, EP4 stimulation decreased elastin/collagen cross-linking protein LOX (lysyl oxidase) in both human and mouse VSMCs. Conclusions: Dysregulated EP4 overexpression in VSMCs promotes inflammatory monocyte/macrophage infiltration and attenuates elastin/collagen fiber formation, leading to AAA exacerbation.

scholarly journals Up-regulated MCPIP1 in abdominal aortic aneurysm is associated with vascular smooth muscle cell apoptosis and MMPs production

2019 ◽  
Vol 39 (11) ◽  
Author(s):  
Ming Xue ◽  
Gang Li ◽  
Dan Li ◽  
Zhu Wang ◽  
Lei Mi ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Vascular Smooth Muscle ◽  
Interleukin 1 ◽  
Ang Ii ◽  
Monocyte Chemotactic Protein ◽  
Abdominal Aortic ◽  
Chemotactic Protein ◽  
Proliferation And Apoptosis

Abstract Abdominal aortic aneurysm (AAA) is often clinically silent before rupture characterized by extensive vascular inflammation and degenerative elasticity of aortic wall. Monocyte chemotactic protein-induced protein-1 (MCPIP1) exhibits anti-infllammatory and pro-apoptotic effects involved in atherogenesis. However, little is known about the expression and the contribution of MCPIP1 in AAA. In the present study, we collected clinical AAA specimens and constructed AAA mice model through Ang-II infusion, and found apparently increased MCPIP1 expression and severe inflammatory infiltration in AAA aortic membrane as evidenced by elevated levels of monocyte chemotactic protein 1 (MCP-1), interleukin 1 β (IL-1β) and NF-κB, as well as HE staining. The elasticity of aortic tunica media was impaired along with multiple apoptosis of vascular smooth muscle cells (VSMCs) in Ang-II-induced aneurysmal mouse. In vitro Ang-II administration of VSMCs induced MCPIP1 expression, accompanied by up-regulation of matrix metalloproteinase (MMP) 2 (MMP-2) and MMP-9, as well as enhancement of VSMCs proliferation and apoptosis, which may cause damage of intima–media elasticity. Silencing MCPIP1 reversed above effects to further restore the balance of proliferation and apoptosis in VSMCs. Overall, our data indicated that up-regulation of MCPIP1 may become a promising candidate for the diagnosis of AAA, and specific knockdown of MCPIP1 in VSMCs could inhibit VSMCs apoptosis and down-regulate MMPs to maintain vascular wall elasticity. Therefore, knockdown of MCPIP1 may serve as a potential target for gene therapy of AAA.

Abstract 47: Caveolin-1 is Critical for Abdominal Aortic Aneurysm Induced by Angiotensin II

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Takashi Obama ◽  
Takehiko Takayanagi ◽  
Kevin J Crawford ◽  
Tomonori Kobayashi ◽  
Victor Rizzo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Smooth Muscle ◽  
Abdominal Aortic Aneurysm ◽  
Angiotensin Ii ◽  
Aortic Aneurysm ◽  
Vascular Smooth Muscle Cells ◽  
Critical Role ◽  
Ang Ii ◽  
Caveolin 1 ◽  
Abdominal Aortic

Abdominal aortic aneurysm (AAA) is a significant cause of mortality for adults aged >60 years. Accumulating evidence suggests a role of angiotensin II (Ang II) in abdominal aortic aneurysm (AAA) formation. However, the Ang II-sensitive proximal signaling events primarily responsible for AAA formation remain unclear. We recently reported that caveolin-1 (Cav1) enriched membrane microdomains in vascular smooth muscle cells (VSMC) mediate a metalloprotease ADAM17-dependent EGF receptor (EGFR) transactivation, which is linked to vascular remodeling induced by Ang II. Given that ADAM17 expression is one of the key features in AAA, we have tested our hypothesis that Cav1, a major structural protein of caveolae, plays a critical role for development of AAA by Ang II via regulation of ADAM17. 8 week old male Cav1-/- and the control C57Bl/6 wild-type mice (WT) were co-infused with Ang II (1 μg/kg/min) and β-aminopropionitrile (BAPN: 150mg/kg/day) for 4 weeks to induce AAA. In WT with the co-infusion, 58% (14/24) were dead due to aortic rupture/dissection. All surviving WT with co-infusion had AAA with max diameter (mm) of 2.6±0.18 vs 0.93±0.09 with saline infusion (p<0.01). In contrast, we found that Cav1-/- with co-infusion did not die or develop AAA. The max diameter (mm) of AAA in Cav1-/- with co-infusion was 1.0±0.04 vs 1.1±0.06 with saline infusion (n=7). In contrast, both WT and Cav1-/- with the co-infusion developed hypertension assessed by telemetry (MAP mmHg: 151±5 vs 161±7). We found an increased expression of ADAM17 by IHC and qPCR, and enhanced phosphorylation of EGFR by IHC in WT abdominal aortae with aneurysms. These events were markedly attenuated in Cav1-/- aorta with co-infusion (ADAM17/18S mRNAx10,000 = 3.08±0.71 vs 0.97±0.42 p<0.05, n=4). Furthermore, Cav1-/- aortae showed less ER and oxidative stress compared to WT aortae assessed by IHC. In addition, Cav1 silencing induced by adenovirus encoding Cav1 targeting siRNA embedded miRNA in cultured vascular smooth muscle cells prevented Ang II-induced ADAM17 induction and activation. In conclusion, Cav1 and presumably vascular caveolae microdomains appear to play a critical role in the formation of AAA by Ang II via regulation of the ADAM17/EGFR signaling and subsequent ER/oxidative stress.

scholarly journals Circular RNA RBM33 contributes to extracellular matrix degradation via miR-4268/EPHB2 axis in abdominal aortic aneurysm

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12232
Author(s):  
Shizhi Wang ◽  
Qingwen Yuan ◽  
Wenpeng Zhao ◽  
Weimin Zhou
Keyword(s):  
Extracellular Matrix ◽  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Matrix Metalloproteinase 2 ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Ang Ii ◽  
Abdominal Aortic ◽  
Gene Assay ◽  
Ecm Degradation

Background Abdominal aortic aneurysm (AAA) is a complex vascular disease involving expansion of the abdominal aorta. Extracellular matrix (ECM) degradation is crucial to AAA pathogenesis, however, the specific molecular mechanism remains unclear. This study aimed to investigate differentially expressed circular RNAs (DEcircRNAs) involved in ECM degradation of AAA. Methods Transcriptome sequencing was used to analyze the DEcircRNAs between the AAA tissues and normal tissues. The expression of circRNAs in tissues and cells was validated using quantitative reverse transcription PCR (RT-qPCR). Overexpression of circRNAs in vascular smooth muscle cells (VSMCs) treated with angiotensin II (Ang II) was employed to explore its effect on ECM degradation of AAA. Bioinformatic technology, luciferase reporter gene assay, RT-qPCR, and rescue experiment were employed to evaluate the regulatory mechanism of circRNA. Results We identified 65 DEcircRNAs in AAA tissues compared with normal abdominal aortic tissues, including 30 up-regulated and 35 down-regulated circRNAs, which were mainly involved in inflammation and ECM-related functions and pathways. Moreover, circRBM33 was significantly increased in AAA tissues and Ang II-induced VSMCs compared with control samples. Overexpression of circRBM33 increased the expression of ECM-related molecule matrix metalloproteinase-2 and reduced the tissue inhibitor of matrix metalloproteinases-1 expression. Mechanistically, miR-4268 targeted binding to circRBM33 and inhibited the luciferase activity of circRBM33. Overexpression of circRBM33 induced the expression of EPH receptor B2 (EPHB2), and this effect was countered by miR-4268 mimics. Conclusions Overall, our data suggest that circRBM33 might be involved in AAA progression by regulating ECM degradation via the miR-4268/EPHB2 axis.

scholarly journals Knockdown of long noncoding RNA GAS5 reduces vascular smooth muscle cell apoptosis by inactivating EZH2-mediated RIG-I signaling pathway in abdominal aortic aneurysm

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Tianming Le ◽  
Xin He ◽  
Jianhua Huang ◽  
Shuai Liu ◽  
Yang Bai ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Rna Binding ◽  
Ectopic Expression ◽  
Tunel Staining ◽  
Ang Ii ◽  
Abdominal Aortic

Abstract Background Abdominal aortic aneurysm (AAA), an irreversible cardiovascular disease prevalent in the artery, causes the increase of the aneurysm diameter over time, and is a fatal phenomenon inducing sidewall rupture. Long noncoding RNAs (lncRNAs) serve as promising biomarkers for AAA. In the present study, we sought to define the role of lncRNA growth-arrest-specific transcript 5 (GAS5) in growth of smooth muscle cells (SMC) and progression of AAA. Methods Initially, we established angiotensin II (Ang II)-induced AAA mouse models and Ang II-treated vascular SMC model. RT-qPCR and Western blot analysis were adopted to determine expression of GAS5 and zeste homolog 2 (EZH2). After ectopic expression and depletion experiments in Ang II-treated mice and vascular SMCs, cell apoptosis was detected in SMCs using flow cytometry and in mice using TUNEL staining. The binding of GAS5 and EZH2 was evaluated using RNA binding protein immunoprecipitation (RIP) and Co-IP assays. Results Increased GAS5 and RIG-I but decreased EZH2 were found in aortic tissues of AAA mice. EZH2 overexpression inhibited AAA formation and suppressed SMC apoptosis. Functionally, EZH2 blocked the RIG-I signaling pathway and consequently inhibited SMC apoptosis. GAS5 regulated EZH2 transcription in a negative manner in SMCs. Knockdown of GAS5 attenuated SMC apoptosis, which was reversed by EZH2 inhibition or RIG-I overexpression. Conclusions The current study demonstrated that GAS5 induced SMC apoptosis and subsequent AAA onset by activating EZH2-mediated RIG-I signaling pathway, highlighting GAS5 as a novel biomarker for AAA.

Abstract 102: Model-Dependent Influence of Prior Splenectomy on Experimental Abdominal Aortic Aneurysm Progression

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Baohui Xu ◽  
Yasunori Iida ◽  
Xiaolei Hu ◽  
Richard Yuan ◽  
Haojun Xuan ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Initial Step ◽  
Aortic Diameter ◽  
Ang Ii ◽  
Elastin Degradation ◽  
Abdominal Aortic

Objective: Abdominal aortic aneurysm (AAA) is a macrophage-driven, inflammatory vascular disease. Thus, mobilization of macrophage precursors from the bone marrow and/or splenic reservoir may represent a crucial initial step for AAA formation. Prior evidence suggests that splenic monocytes are important initial contributors to ischemic myocardial injury, their role in AAA pathogenesis remains unknown. We surgically removed the spleen prior to AAA creation to evaluate the influence of splenic monocytes on aneurysm pathophysiology. Methods: AAAs were created in either 1) male C57BL/6 mice by infrarenal intra-aortic porcine pancreatic elastase (PPE) infusion or 2) male ApoE deficient mice by continuous subdermal angiotensin II infusion (ApoE KO/Ang II model). Splenectomy was performed immediately prior to AAA creation in both models. Aortic diameter was serially monitored via ultrasonography, and aortae harvested at sacrifice for histopathology. Results: In sham splenectomy mice, PPE infusion led to significant aortic enlargement. AAA (≥50% aortic diameter increase) developed in all sham/PPE mice within 14 days (n=10). Splenectomy effectively eliminated PPE-induced aortic enlargement, with preservation of medial elastin and smooth muscle cell density and minimal inflammation compared to sham. In contrast, Ang II infusion in ApoE deficient produced similar-sized or larger AAA in splenectomized mice compared to sham, with elastin degradation, smooth muscle cell depletion undistinguishable between the groups. Conclusion: Splenectomy confers differential protection from AAA in mice, depending on the model/method employed for aneurysm formation. While this experiment underscores important limitations to mouse-based AAA modeling, the splenic monocyte reservoir may represent an important driver of AAA pathophysiology.

scholarly journals Catalase overexpression in aortic smooth muscle prevents pathological mechanical changes underlying abdominal aortic aneurysm formation

2011 ◽  
Vol 301 (2) ◽  
pp. H355-H362 ◽  
Author(s):  
Kathryn Maiellaro-Rafferty ◽  
Daiana Weiss ◽  
Giji Joseph ◽  
William Wan ◽  
Rudolph L. Gleason ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Circumferential Strain ◽  
Opening Angle ◽  
Ang Ii ◽  
Growth And Remodeling ◽  
Aortic Smooth Muscle ◽  
Abdominal Aortic ◽  
Mechanical Remodeling

The causality of the associations between cellular and mechanical mechanisms of abdominal aortic aneurysm (AAA) formation has not been completely defined. Because reactive oxygen species are established mediators of AAA growth and remodeling, our objective was to investigate oxidative stress-induced alterations in aortic biomechanics and microstructure during subclinical AAA development. We investigated the mechanisms of AAA in an angiotensin II (ANG II) infusion model of AAA in apolipoprotein E-deficient (apoE−/−) mice that overexpress catalase in vascular smooth muscle cells (apoE−/−xTgSMC-Cat). At baseline, aortas from apoE−/−xTgSMC-Cat exhibited increased stiffness and the microstructure was characterized by 50% more collagen content and less elastin fragmentation. ANG II treatment for 7 days in apoE−/− mice altered the transmural distribution of suprarenal aortic circumferential strain (quantified by opening angle, which increased from 130 ± 1° at baseline to 198 ± 8° after 7 days of ANG II treatment) without obvious changes in the aortic microstructure. No differences in aortic mechanical behavior or suprarenal opening angle were observed in apoE−/−xTgSMC-Cat after 7 days of ANG II treatment. These data suggest that at the earliest stages of AAA development H2O2 is functionally important and is involved in the control of local variations in remodeling across the vessel wall. They further suggest that reduced elastin integrity at baseline may predispose the abdominal aorta to aneurysmal mechanical remodeling.

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