Lessons Learned From RAG-1-Deficient Mice in Hypertension

Montezano, Augusto C; Touyz, Rhian M.

doi:10.1161/hypertensionaha.119.14406

Cited by 6 publications

(2 citation statements)

References 14 publications

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“…There is no doubt that lymphocytes play a role in hypertension. The negative data illustrate that there are important, but still unidentified confounders (Madhur et al, 2020;Rios et al, 2020).…”

Section: Immune Cells In Cardiovascular Diseasementioning

confidence: 99%

The role of the mineralocorticoid receptor in immune cells in cardiovascular disease

Heijden

Bode

Riksen

et al. 2022

British J Pharmacology

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Chronic low-grade inflammation and immune cell activation are important mechanisms in the pathophysiology of cardiovascular disease (CVD). Therefore, targeted immunosuppression is a promising novel therapy to reduce cardiovascular risk. In this review, we identify the mineralocorticoid receptor (MR) on immune cells as a potential target to modulate inflammation. The MR is present in almost all cells of the cardiovascular system, including immune cells. Activation of the MRs in innate and adaptive immune cells induces inflammation which can contribute to CVD, by inducing endothelial dysfunction and hypertension. Moreover, it accelerates atherosclerotic plaque formation and destabilization and impairs tissue regeneration after ischaemic events. Identifying the molecular targets for these non-renal actions of the MR provides promising novel cardiovascular drug targets for mineralocorticoid receptor antagonists (MRAs), which are currently mainly applied in hypertension and heart failure.

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Section: Immune Cells In Cardiovascular Diseasementioning

confidence: 99%

The role of the mineralocorticoid receptor in immune cells in cardiovascular disease

Heijden

Bode

Riksen

et al. 2022

British J Pharmacology

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show abstract

“…While it is clear that lymphocytes play a critical role in hypertension, the negative data illustrate that there are important but unidentified confounders. Possible confounders range from the loss of phenotype due to compensatory mechanisms in the immune system over generations of laboratory breeding to undiscovered environmental factors, which might change over time and between different laboratories, such as regular chow and/or alterations in the microbiota [ 63 , 66 , 67 ]. Under the hypothesis of compensatory mechanisms, one could even consider on the possibly of even greater importance of the immune system in BP regulation since it seems to be able to regain its effect on BP after initial knockout.…”

Section: The Immune System and Hypertensionmentioning

confidence: 99%

Mosaic theory revised: inflammation and salt play central roles in arterial hypertension

2022

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The mosaic theory of hypertension was advocated by Irvine Page ~80 years ago and suggested that hypertension resulted from the close interactions of different causes. Increasing evidence indicates that hypertension and hypertensive end-organ damage are not only mediated by the proposed mechanisms that result in hemodynamic injury. Inflammation plays an important role in the pathophysiology and contributes to the deleterious consequences of arterial hypertension. Sodium intake is indispensable for normal body function but can be detrimental when it exceeds dietary requirements. Recent data show that sodium levels also modulate the function of monocytes/macrophages, dendritic cells, and different T-cell subsets. Some of these effects are mediated by changes in the microbiome and metabolome due to high-salt intake. The purpose of this review is to propose a revised and extended version of the mosaic theory by summarizing and integrating recent advances in salt, immunity, and hypertension research. Salt and inflammation are placed in the middle of the mosaic because both factors influence each of the remaining pieces.

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Monitoring mouse papillomavirus-associated cancer development using longitudinal Pap smear screening

Atkins,

Uslu,

et al. 2024

mBio

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A substantial percentage of the population remains at risk for cervical cancer due to pre-existing human papillomavirus (HPV) infections, despite prophylactic vaccines. Early diagnosis and treatment are crucial for better disease outcomes. The development of new treatments heavily relies on suitable preclinical model systems. Recently, we established a mouse papillomavirus (MmuPV1) model that is relevant to HPV genital pathogenesis. In the current study, we validated the use of Papanicolaou (Pap) smears, a valuable early diagnostic tool for detecting HPV cervical cancer, to monitor disease progression in the MmuPV1 mouse model. Biweekly cervicovaginal swabs were collected from the MmuPV1-infected mice for viral DNA quantitation and cytology assessment. The Pap smear slides were evaluated for signs of epithelial cell abnormalities using the 2014 Bethesda system criteria. Tissues from the infected mice were harvested at various times post-viral infection for additional histological and virological assays. Over time, increased viral replication was consistent with higher levels of viral DNA, and it coincided with an uptick in epithelial cell abnormalities with higher severity scores noted as early as 10 weeks after viral infection. The cytological results also correlated with the histological evaluation of tissues harvested simultaneously. Both immunocompromised and immunocompetent mice with squamous cell carcinoma (SCC) cytology also developed vaginal SCCs. Notably, samples from the MmuPV1-infected mice exhibited similar cellular abnormalities compared to the corresponding human samples at similar disease stages. Hence, Pap smear screening proves to be an effective tool for the longitudinal monitoring of disease progression in the MmuPV1 mouse model. IMPORTANCE Papanicolaou (Pap) smear has saved millions of women's lives as a valuable early screening tool for detecting human papillomavirus (HPV) cervical precancers and cancer. However, more than 200,000 women in the United States alone remain at risk for cervical cancer due to pre-existing HPV infection-induced precancers, as there are currently no effective treatments for HPV-associated precancers and cancers other than invasive procedures including a loop electrosurgical excision procedure (LEEP) to remove abnormal tissues. In the current study, we validated the use of Pap smears to monitor disease progression in our recently established mouse papillomavirus model. To the best of our knowledge, this is the first study that provides compelling evidence of applying Pap smears from cervicovaginal swabs to monitor disease progression in mice. This HPV-relevant cytology assay will enable us to develop and test novel antiviral and anti-tumor therapies using this model to eliminate HPV-associated diseases and cancers.

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Lessons Learned From RAG-1-Deficient Mice in Hypertension

Cited by 6 publications

References 14 publications

The role of the mineralocorticoid receptor in immune cells in cardiovascular disease

The role of the mineralocorticoid receptor in immune cells in cardiovascular disease

Mosaic theory revised: inflammation and salt play central roles in arterial hypertension

Monitoring mouse papillomavirus-associated cancer development using longitudinal Pap smear screening

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