The C57Bl/6J mouse strain is more susceptible to angiotensin II-induced aortic aneurysm formation than C57Bl/6N

Wortmann, Markus; Arshad, Muhammad; Peters, Andreas S.; Hakimi, Maani; Böckler, Dittmar; Dihlmann, Susanne

doi:10.1016/j.atherosclerosis.2020.11.032

Cited by 16 publications

(25 citation statements)

References 6 publications

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“…Elastin fragments could induce NFkB activation and IL-1β upregulation-a prime condition for inflammasome activation [105]. Moreover, mitochondrial derived oxidative stress that was found to induce an inflammsome response in macrophages [50] and VSMC [54] of mouse aneurysms, is expexted to increase during aging, thereby creating an adverse feed forward (vicious) cycle of inflammation and oxida-tive stress [106]. Similarly, AGEs react with their receptor RAGE to activate NF-κB-driven inflammation and oxidative stress in vascular cells, which further increases production of AGEs [107].…”

Section: Discussionmentioning

confidence: 99%

“…Similar to the observation in macrophages, oxidative stress in mitochondria of VSMC is associated with the induction of inflammasome proteins in AAA tissue. By using two wildtype strains, differing in the function of the mitochondrial gene nicotinamide-nucleotidetranshydrogenase (Nnt), we found increased protein expression of Nlrp3, Aim2, Asc and Caspase-1 in VSMC of the Nnt-deficient mouse strain, along with higher levels of oxidative DNA damage and an increased incidence of AngII-induced aortic aneurysm [54].…”

Section: Pre-clinical and Functional Studies Suggest A Causal Role Of Inflammasome Signaling In The Development Of Aortic Aneurysmmentioning

confidence: 99%

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Inflammasomes in the Pathophysiology of Aortic Disease

Wortmann

Peters

Erhart

et al. 2021

Cells

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Aortic diseases comprise aneurysms, dissections, and several other pathologies. In general, aging is associated with a slow but progressive dilation of the aorta, along with increased stiffness and pulse pressure. The progression of aortic disease is characterized by subclinical development or acute presentation. Recent evidence suggests that inflammation participates causally in different clinical manifestations of aortic diseases. As of yet, diagnostic imaging and surveillance is mainly based on ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI). Little medical therapy is available so far to prevent or treat the majority of aortic diseases. Endovascular therapy by the introduction of covered stentgrafts provides the main treatment option, although open surgery and implantation of synthetic grafts remain necessary in many situations. Because of the risks associated with surgery, there is a need for identification of pharmaceutical targets interfering with the pathophysiology of aortic remodeling. The participation of innate immunity and inflammasome activation in different cell types is common in aortic diseases. This review will thus focus on inflammasome activities in vascular cells of different chronic and acute aortic diseases and discuss their role in development and progression. We will also identify research gaps and suggest promising therapeutic targets, which may be used for future medical interventions.

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Section: Discussionmentioning

confidence: 99%

Section: Pre-clinical and Functional Studies Suggest A Causal Role Of Inflammasome Signaling In The Development Of Aortic Aneurysmmentioning

confidence: 99%

Inflammasomes in the Pathophysiology of Aortic Disease

Wortmann

Peters

Erhart

et al. 2021

Cells

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“…The C57BL/6J and C57BL/6N substrains have well-defined differences, including the recently demonstrated diversity in the development of aortopathies. 67 , 68 It is also important to consider different mouse strains when designing an experiment because the strains have different susceptibilities to BAPN-induced AAD. Male FVB mice had a lower incidence of AAD compared with age-matched male C57BL/6 mice (substrain not reported): a 25% incidence of AAD and no aortic rupture in FVB mice vs an 87% incidence of AAD and a 37% incidence of aortic rupture in C57BL/6 mice.…”

Section: Development Of Bapn-induced Aad In Micementioning

confidence: 99%

β-Aminopropionitrile-induced aortic aneurysm and dissection in mice

Sawada

Beckner

Ito

et al. 2022

JVS-Vascular Science

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The mechanistic basis for the formation of aortic aneurysms and dissection needs to be elucidated to facilitate the development of effective medications. β-Aminopropionitrile administration in mice has been used frequently to study the pathologic features and mechanisms of aortic aneurysm and dissection. This mouse model mimics several facets of the pathology of human aortic aneurysms and dissection, although many variables exist in the experimental design and protocols that must be resolved to determine its application to the human disease. In the present brief review, we have introduced the development of this mouse model and provided insights into understanding its pathologic features.

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“…Based on studies between the B6J and B6N mice, NNT expression has been linked to cardiomyopathy, hypertension, atherosclerosis and diabetes [ 7 , 19 , 20 , 21 , 22 ]. Furthermore, groups have found differences in cardiac remodelling between these substrains in response to stressors such as exercise, aortic banding and angiotensin, although there are conflicting data for the latter [ 21 , 23 , 24 ]. Nnt has often been posited as the causative gene for these phenotypes, as it is by far the best known and best studied genomic difference between the two strains.…”

Section: Introductionmentioning

confidence: 99%

Loss of Nnt Increases Expression of Oxidative Phosphorylation Complexes in C57BL/6J Hearts

Williams

Hall

Meimaridou

et al. 2021

IJMS

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Nicotinamide nucleotide transhydrogenase (NNT) is a proton pump in the inner mitochondrial membrane that generates reducing equivalents in the form of NAPDH, which can be used for anabolic pathways or to remove reactive oxygen species (ROS). A number of studies have linked NNT dysfunction to cardiomyopathies and increased risk of atherosclerosis; however, biallelic mutations in humans commonly cause a phenotype of adrenal insufficiency, with rare occurrences of cardiac dysfunction and testicular tumours. Here, we compare the transcriptomes of the hearts, adrenals and testes from three mouse models: the C57BL/6N, which expresses NNT; the C57BL/6J, which lacks NNT; and a third mouse, expressing the wild-type NNT sequence on the C57BL/6J background. We saw enrichment of oxidative phosphorylation genes in the C57BL/B6J in the heart and adrenal, possibly indicative of an evolved response in this substrain to loss of Nnt. However, differential gene expression was mainly driven by mouse background with some changes seen in all three tissues, perhaps reflecting underlying genetic differences between the C57BL/B6J and -6N substrains.

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The C57Bl/6J mouse strain is more susceptible to angiotensin II-induced aortic aneurysm formation than C57Bl/6N

Cited by 16 publications

References 6 publications

Inflammasomes in the Pathophysiology of Aortic Disease

Inflammasomes in the Pathophysiology of Aortic Disease

β-Aminopropionitrile-induced aortic aneurysm and dissection in mice

Loss of Nnt Increases Expression of Oxidative Phosphorylation Complexes in C57BL/6J Hearts

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