Chimeric renin-angiotensin system demonstrates sustained increase in blood pressure of transgenic mice carrying both human renin and human angiotensinogen genes

Fukamizu, Akiyoshi; Sugimura, Keiichi; Takimoto, Eriko; Sugiyama, Fumihiro; Seo, Min-Seok; Takahashi, Saori; Hatae, Toshihisa; Kajiwara, Noriko; Yagami, Ken‐ichi; Murakami, Kazuo

doi:10.1016/s0021-9258(19)50246-0

Cited by 249 publications

(18 citation statements)

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“…Substantially similar results were obtained in transgenic mice receiving the rat AGT gene [96]. Transgenic mice carrying both the human renin and the human AGT genes under the control of their native promoters have high blood pressure and may be a good model for human high renin hypertension [97]. Disruption of the angiotensin converting enzyme (ACE) gene in mice reduced blood pressure by about 50% and serum ACE activity to zero [98], whereas when only one functional allele was left blood pressure remained normal, ACE activity was reduced by about 50% and renal renin mRNA increased fourfold [99].…”

Section: Ss/jr ϫ Lew Agtsupporting

confidence: 60%

“…It may carry a putative pathogenic mutation or alternatively may restore the healthy allele, so that one may test the hypothesis that a specific candidate gene causes the disease. Transgenic rats created by microinjection of the mouse renin-2 gene into non-hypertensive non-inbred Sprague-Dawley rats have fulminant hypertension, low plasma renin, enhanced corticosteroids secretion and several other developmental and regulatory abnormalities [97]. Mice carrying from 0 to 4 functional copies of the murine wild-type angiotensinogen (AGT) gene at its normal chromosomal location have a significant and almost linear increase in blood pressure and serum AGT concentration per gene copy, although the normal compensatory mechanisms are intact [95].…”

Section: Ss/jr ϫ Lew Agtmentioning

confidence: 99%

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A primer on the genetics of hypertension

Cusi

Bianchi

1998

Kidney International

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Section: Ss/jr ϫ Lew Agtsupporting

confidence: 60%

Section: Ss/jr ϫ Lew Agtmentioning

confidence: 99%

A primer on the genetics of hypertension

Cusi

Bianchi

1998

Kidney International

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“…Further modifications resulted in female mice overexpressing both renin and angiotensinogen, being hypertensive before pregnancy, making them a more suitable model to represent women who enter pregnancy hypertensive (mean blood pressure increased~34 mmHg) and later develop preeclampsia (25,30,32). These pregnant mice developed proteinuria by late pregnancy with no sign of changes to renal pathology, increased necrosis of the placenta, smaller pup weights, increased placental mRNA expression of sFlt-1, and increased circulating levels of sFlt-1.…”

Section: Animal Models Of Preeclampsiamentioning

confidence: 99%

Animal models of preeclampsia: translational failings and why

Marshall

Hannan

Jelinic

et al. 2018

American Journal of Physiology-Regulatory, Integrative and Comp

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Preeclampsia affects up to 8% of pregnancies worldwide and is a leading cause of both maternal and fetal morbidity and mortality. Our current understanding of the cause(s) of preeclampsia is far from complete, and the lack of a single reliable animal model that recapitulates all aspects of the disease further confounds our understanding. This is partially due to the heterogeneous nature of the disease, coupled with our evolving understanding of its etiology. Nevertheless, animal models are still highly relevant and useful tools that help us better understand the pathophysiology of specific aspects of preeclampsia. This review summarizes the various types and characteristics of animal models used to study preeclampsia, highlighting particular features of these models relevant to clinical translation. This review points out the strengths and limitations of these models to illustrate the importance of using the appropriate model depending on the research question.

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“…Blood pressure and heart rate were measured under conscious and unrestrained conditions using a programmable sphygmomanometer (BP-98A; Softron, Tokyo, Japan) and the tail cuff method [ 19 ]. Unanesthetized mice were introduced into a small holder mounted on a thermostatically controlled warming plate and maintained at 37 °C during the measurements.…”

Section: Methodsmentioning

confidence: 99%

Maternal High-Fat Diet Promotes Abdominal Aortic Aneurysm Expansion in Adult Offspring by Epigenetic Regulation of IRF8-Mediated Osteoclast-like Macrophage Differentiation

Saburi

Yamada

Wada

et al. 2021

Cells

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Maternal high-fat diet (HFD) modulates vascular remodeling in adult offspring. Here, we investigated the impact of maternal HFD on abdominal aortic aneurysm (AAA) development. Female wild-type mice were fed an HFD or normal diet (ND). AAA was induced in eight-week-old pups using calcium chloride. Male offspring of HFD-fed dams (O-HFD) showed a significant enlargement in AAA compared with the offspring of ND-fed dams (O-ND). Positive-staining cells for tartrate-resistant acid phosphate (TRAP) and matrix metalloproteinase (MMP) activity were significantly increased in O-HFD. The pharmacological inhibition of osteoclastogenesis abolished the exaggerated AAA development in O-HFD. The in vitro tumor necrosis factor-α-induced osteoclast-like differentiation of bone marrow-derived macrophages showed a higher number of TRAP-positive cells and osteoclast-specific gene expressions in O-HFD. Consistent with an increased expression of nuclear factor of activated T cells 1 (NFATc1) in O-HFD, the nuclear protein expression of interferon regulatory factor 8 (IRF8), a transcriptional repressor, were much lower, with significantly increased H3K27me3 marks at the promoter region. The enhancer of zeste homolog 2 inhibitor treatment restored IRF8 expression, resulting in no difference in NFATc1 and TRAP expressions between the two groups. Our findings demonstrate that maternal HFD augments AAA expansion, accompanied by exaggerated osteoclast-like macrophage accumulation, suggesting the possibility of macrophage skewing via epigenetic reprogramming.

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Chimeric renin-angiotensin system demonstrates sustained increase in blood pressure of transgenic mice carrying both human renin and human angiotensinogen genes

Cited by 249 publications

References 0 publications

A primer on the genetics of hypertension

A primer on the genetics of hypertension

Animal models of preeclampsia: translational failings and why

Maternal High-Fat Diet Promotes Abdominal Aortic Aneurysm Expansion in Adult Offspring by Epigenetic Regulation of IRF8-Mediated Osteoclast-like Macrophage Differentiation

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