Whole genome expression analysis within the angiotensin II-apolipoprotein E deficient mouse model of abdominal aortic aneurysm

Rush, Catherine M.; Nyara, Moses; Moxon, Joseph V.; Trollope, Alexandra F.; Cullen, Bradford; Golledge, Jonathan

doi:10.1186/1471-2164-10-298

Cited by 92 publications

(104 citation statements)

References 37 publications

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“…Various studies in humans and animals have shown the implication of UCNs in different cardiovascular disorders, such as atherosclerosis, myocardial infarct and heart failure [97,99,100]; however, its role on AAA has only been reported very recently [101,102]. The first evidence associating the UCNs to AAA was documented by Rush et al [102].…”

Section: Urocortinmentioning

confidence: 95%

“…Using the Ang II-infused ApoE-/-mouse AAA model, they investigated genes that were differentially expressed in the aneurysm prone segment of aorta. Interestingly, UCN3 gene expression was downregulated in the suprarenal region of the aorta (susceptive to aneurysm formation in mice) compared to the infrarenal region (resistant to aneurysm formation in mice) [102], raising the speculation that UCNs have a protective function against AAA. In another study, the same group reported that UCN2 and CRFR2 gene expression were significantly higher in the most dilated part of the human AAA compared to the non-dilated proximal neck of the AAA [101].…”

Section: Urocortinmentioning

confidence: 99%

“…The first evidence associating the UCNs to AAA was documented by Rush et al [102]. Using the Ang II-infused ApoE-/-mouse AAA model, they investigated genes that were differentially expressed in the aneurysm prone segment of aorta.…”

Section: Urocortinmentioning

confidence: 99%

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Emerging Pharmacological Treatments to Prevent Abdominal Aortic Aneurysm Growth and Rupture

Fraga‐Silva

Trachet²,

Stergiopulos³

2015

CPD

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Abdominal aortic aneurysm (AAA) is a local expansion of the abdominal aorta wall caused by a complex multifactorial maladaptive vascular remodeling. Despite recent advances in the management of cardiovascular diseases, there currently is no established drug therapy for AAA. Since the probability of death from a ruptured AAA still remains high, preventive elective repair of AAAs larger than 5.5 cm in luminal diameter is considered the best treatment option. However, perioperative complications are problematic as elective AAA repair comes with numerous intrinsic risks. Impelled by the need of improving AAA therapy, significant efforts have been made to identify pharmacological tools that would slow down AAA enlargement and lower the risk of rupture, thereby reducing the necessity of surgical intervention. In this review, we discuss recent findings addressing molecular targets that could potentially treat AAA, particularly addressing: statins, classical renin angiotensin system (RAS) blockers, the protective arm of RAS, renin inhibitors, tetracyclines, interleukin-1β inhibition, anti-angiogenic agents and urocortins.

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Section: Urocortinmentioning

confidence: 95%

Section: Urocortinmentioning

confidence: 99%

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Emerging Pharmacological Treatments to Prevent Abdominal Aortic Aneurysm Growth and Rupture

Fraga‐Silva

Trachet²,

Stergiopulos³

2015

CPD

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“…The evidence published to date relates to the aorta. In an angiotensin IIeinduced mouse model of abdominal aortic aneurysm, the aneurysm-prone segment showed increased Tgf-b expression, 31 and systemic neutralization of the Tgf-b activity markedly accelerated the progression of the aneurysm and its complications. 32 In a mouse model of aortic stenosis and heart failure induced by aortic banding, there was increased Tgf-b signaling, and treatment with SM16ddespite reducing myocardial fibrosis and ameliorating functiondeventually accelerated the death of the mice by causing aortic rupture at the banded site.…”

Section: Discussionmentioning

confidence: 99%

The Increased Transforming Growth Factor-β Signaling Induced by Diabetes Protects Retinal Vessels

Dagher

Gerhardinger

Vaz

et al. 2017

The American Journal of Pathology

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The roles of transforming growth factor (TGF)-b in extracellular matrix production and vascular remodeling, coupled with increased TGF-b expression and signaling in diabetes, suggest TGF-b as an important contributor to the microangiopathy of diabetic retinopathy and nephropathy. To investigate whether increased TGF-b signaling could be a therapeutic target for preventing retinopathy, we used a pharmacologic approach (SM16, a selective inhibitor of the type 1 TGF-b receptor activin receptorelike kinase 5, orally active) to inhibit the increased, but not the basal, Tgf-b signaling in retinal vessels of diabetic rats. At the level of vascular gene expression, 3.5 months' diabetes induced minimal changes. Diabetes þ SM16 for 3 weeks caused widespread changes in gene expression poised to enhance vascular inflammation, thrombosis, leakage, and wall instability; these changes were not observed in control rats given SM16. The synergy of diabetes and SM16 in altering gene expression was not observed in the lung. At the level of vascular network morphology, 7 months' diabetes induced no detectable changes. Diabetes þ SM16 for 3 weeks caused instead distorted morphology and decreased density. Thus, in diabetes, retinal vessels become dependent on a small increase in TGF-b signaling via activin receptorelike kinase 5 to maintain early integrity. The increased TGF-b signaling may protect against rapid retinopathy progression and should not be a target of inhibitory interventions. (Am J Pathol 2017, 187: 627e638; http://dx

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“…46 Microarrays and real time PCR will be used to assess circulating cell markers as previously described. 47 Ultrasound measurements will be undertaken at entry and 24 weeks by experienced sonographers within the vascular laboratories at each study centre. The sonographers will measure the maximum diameters of the infrarenal aorta perpendicular to blood flow while the participant is in supine and lateral decubitus position.…”

mentioning

confidence: 99%

Fenofibrate in the management of AbdoMinal aortic aneurysm (FAME)-2: the study protocol for a multi-centre, randomised, placebo-controlled trial

Rowbotham

Bourke

et al. 2016

Int J Clin Trials

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INTRODUCTIONAn abdominal aortic aneurysm (AAA) is a permanent dilatation of the infrarenal aorta that can lead to death as a result of aortic rupture.1,2 AAAs are present in ~5% of men and ~1% of women aged over 65 years, but have no known medical therapy. [3][4][5][6][7] Current guidelines comprise regular ultrasound imaging until a diameter threshold is reached (typically 55 mm), at which point surgical intervention is considered. 8 Patients with symptomatic or rapidly expanding AAAs (>10 mm/year) should also be ABSTRACT Background: Abdominal aortic aneurysms (AAAs) are a leading cause of mortality worldwide but have no recognised medical therapy. Pre-clinical studies indicate that osteopontin plays an important role in the pathogenesis of AAA via a number of mechanisms. This trial aims to assess the potential of fenofibrate to favourably alter biomarkers associated with AAA pathology. Methods: Fenofibrate in the management of AbdoMinal aortic anEurysm (FAME)-2 is a multi-centre, prospective, randomised, double-blind, placebo-controlled clinical trial to assess the effect of 24 weeks of oral therapy with 145 mg of fenofibrate on key pathological markers of AAA. A total of 140 participants with an AAA measuring between 35-49 mm will be randomly assigned to either 145 mg of fenofibrate once per day or identical placebo for a period of 24 weeks. Primary outcome measures will be serum concentrations of osteopontin and kallistatin. Secondary outcome measures will include serum levels of resistin, lipids, matrix metalloproteinases and pro-inflammatory cytokines, circulating concentrations of AAA biomarkers, and AAA diameter as assessed by ultrasound. Conclusions: This study represents the next step in the assessment of a potential novel medical therapy for AAA.

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Whole genome expression analysis within the angiotensin II-apolipoprotein E deficient mouse model of abdominal aortic aneurysm

Cited by 92 publications

References 37 publications

Emerging Pharmacological Treatments to Prevent Abdominal Aortic Aneurysm Growth and Rupture

Emerging Pharmacological Treatments to Prevent Abdominal Aortic Aneurysm Growth and Rupture

The Increased Transforming Growth Factor-β Signaling Induced by Diabetes Protects Retinal Vessels

Fenofibrate in the management of AbdoMinal aortic aneurysm (FAME)-2: the study protocol for a multi-centre, randomised, placebo-controlled trial

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