CrossTalk opposing view: The mouse SuHx model is not a good model of pulmonary arterial hypertension

Vitali, Sally H.

doi:10.1113/jp275865

Cited by 5 publications

(5 citation statements)

References 26 publications

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“…However, the extent of fibrosis in the hypoxia + Veh group was not as severe as expected because hypoxia-induced PH progressed more slowly, and thus, only pulmonary changes appeared for the time being. [22][23][24] Oxidative stress and inflammation are mutually reinforcing; therefore, the expressions of inflammatory factors in lung tissue and serum were first detected to preliminarily examine the effect of HCA on oxidative stress. It was found that the expression of inflammatory factors in PH induced by MCT or hypoxia increased, indicating that inflammation is an essential part of the pathogenesis of PH.…”

Section: Discussionmentioning

confidence: 99%

Hydroxycitric Acid Tripotassium Hydrate Attenuates Monocrotaline and Hypoxia-Induced Pulmonary Hypertension in Rats

Wang,

Li,

Liu

et al. 2024

Int. Heart J.

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This study investigated the effects of hydroxycitric acid tripotassium hydrate on right ventricular function, myocardial and pulmonary vascular remodeling in rats with pulmonary hypertension, and possible mechanisms. Methods: Pulmonary hypertension was induced in male Sprague-Dawley rats by a single subcutaneous injection of monocrotaline or hypoxic chamber. In vivo, inflammatory cytokine (including TNF-α, IL-1β, IL-6, and TGFβ, the level of SOD) expression, superoxide dismutase and hydrogen peroxide levels, and p-IκBα and p65 expressions were detected. In vitro, pulmonary artery smooth muscle cell proliferation and migration, ROS production, and hypoxia-inducible factor-1 expression were also studied. Results: Hydroxycitric acid tripotassium hydrate decreased right ventricular systolic pressure and reduced right ventricular fibrosis and pulmonary vascular remodeling in rats with two kinds of pulmonary hypertension. Moreover, the expression of both inflammatory and oxidative stress factors was effectively reduced, and the p65 signaling pathway was found to be inhibited in this study. Additionally, hydroxycitric acid tripotassium hydrate inhibited human pulmonary artery smooth cell proliferation and migration in vitro. Conclusions: This study shows that hydroxycitric acid tripotassium hydrate can alleviate pulmonary hypertension caused by hypoxia and monocycloline in rats, improve remodeling of the right ventricle and pulmonary artery, and inhibit pulmonary artery smooth muscle cell proliferation and migration. The protective effects may be achieved by regulating inflammation and oxidative stress through the p65 signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Hydroxycitric Acid Tripotassium Hydrate Attenuates Monocrotaline and Hypoxia-Induced Pulmonary Hypertension in Rats

Wang,

Li,

Liu

et al. 2024

Int. Heart J.

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“…Here we report the development of an FCG model in laboratory rats (Rattus norvegicus) as a second species in which sex chromosome effects can be studied with relative ease. Rats have many advantages as a model species because of the vast literature on rat sex differences, their greater utility in some models of human disease, and their larger size [19][20][21][22]. Transgenesis is used increasingly in rats, and rat genomic and epigenomic resources are being rapidly developed [23][24][25][26][27][28].…”

Section: Introductionmentioning

confidence: 99%

A “Four Core Genotypes” rat model to distinguish mechanisms underlying sex-biased phenotypes and diseases

Arnold¹,

Chen²,

Grzybowski³

et al. 2023

Preprint

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Background: We have generated a rat model similar to the Four Core Genotypes mouse model, allowing comparison of XX and XY rats with the same type of gonad. The model detects novel sex chromosome effects (XX vs. XY) that contribute to sex differences in any rat phenotype. Methods: XY rats were produced with an autosomal transgene of Sry, the testis-determining factor gene, which were fathers of XX and XY progeny with testes. In other rats, CRISPR-Cas9 technology was used to remove Y chromosome factors that initiate testis differentiation, producing fertile XY gonadal females that have XX and XY progeny with ovaries. These groups can be compared to detect sex differences caused by sex chromosome complement (XX vs. XY) and/or by gonadal hormones (rats with testes vs. ovaries). Results: We have measured numerous phenotypes to characterize this model, including gonadal histology, breeding performance, anogenital distance, levels of reproductive hormones, body and organ weights, and central nervous system sexual dimorphisms. Serum testosterone levels were comparable in adult XX and XY gonadal males. Numerous phenotypes previously found to be sexually differentiated by the action of gonadal hormones were found to be similar in XX and XY rats with the same type of gonad, suggesting that XX and XY rats with the same type of gonad have comparable levels of gonadal hormones at various stages of development. Conclusion: The results establish a powerful new model to discriminate sex chromosome and gonadal hormone effects that cause sexual differences in rat physiology and disease.

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“…Due to the current trend of using polypharmacological approaches in PH treatment, together with the proven beneficial effects of CBD in various PH models as a consequence of its antioxidant and anti-inflammatory properties, the aim of the study was to evaluate the effect of CBD on the selected parameters of oxidative stress and inflammation in the lungs of rats with MCT-induced PH. Although previous studies suggest that CBD may have anti-inflammatory potential in the mouse model of Sugen-hypoxia-induced PH [ 16 ], it has been recently reported that the Sugen-hypoxia model is not preferable in mice, since they display very modest vascular remodeling compared to rats [ 17 , 18 , 19 ]. In this respect, both pulmonary vascular remodeling and PH are reversible, and no characteristic perivascular infiltration of monocytes/macrophages is observed [ 17 , 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

“…Although previous studies suggest that CBD may have anti-inflammatory potential in the mouse model of Sugen-hypoxia-induced PH [ 16 ], it has been recently reported that the Sugen-hypoxia model is not preferable in mice, since they display very modest vascular remodeling compared to rats [ 17 , 18 , 19 ]. In this respect, both pulmonary vascular remodeling and PH are reversible, and no characteristic perivascular infiltration of monocytes/macrophages is observed [ 17 , 18 , 19 ]. The MCT-induced PH model in rats is more recommended because it particularly shows the role of inflammation in the development of PH, and allows the development of damage to pulmonary vessel endothelia with the characteristic perivasculitis [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Cannabidiol Improves Antioxidant Capacity and Reduces Inflammation in the Lungs of Rats with Monocrotaline-Induced Pulmonary Hypertension

et al. 2022

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Cannabidiol (CBD) is a plant-derived compound with antioxidant and anti-inflammatory properties. Pulmonary hypertension (PH) is still an incurable disease. CBD has been suggested to ameliorate monocrotaline (MCT)-induced PH, including reduction in right ventricular systolic pressure (RVSP), a vasorelaxant effect on pulmonary arteries and a decrease in the white blood cell count. The aim of our study was to investigate the effect of chronic administration of CBD (10 mg/kg daily for 21 days) on the parameters of oxidative stress and inflammation in the lungs of rats with MCT-induced PH. In MCT-induced PH, we found a decrease in total antioxidant capacity (TAC) and glutathione level (GSH), an increase in inflammatory parameters, e.g., tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), nuclear factor kappa B (NF-κB), monocyte chemoattractant protein-1 (MCP-1), and cluster of differentiation 68 (CD68), and the overexpression of cannabinoid receptors type 1 and 2 (CB1-Rs, CB2-Rs). Administration of CBD increased TAC and GSH concentrations, glutathione reductase (GSR) activity, and decreased CB1-Rs expression and levels of inflammatory mediators such as TNF-α, IL -1β, NF-κB, MCP-1 and CD68. In conclusion, CBD has antioxidant and anti-inflammatory effects in MCT-induced PH. CBD may act as an adjuvant therapy for PH, but further detailed preclinical and clinical studies are recommended to confirm our promising results.

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CrossTalk opposing view: The mouse SuHx model is not a good model of pulmonary arterial hypertension

Cited by 5 publications

References 26 publications

Hydroxycitric Acid Tripotassium Hydrate Attenuates Monocrotaline and Hypoxia-Induced Pulmonary Hypertension in Rats

Hydroxycitric Acid Tripotassium Hydrate Attenuates Monocrotaline and Hypoxia-Induced Pulmonary Hypertension in Rats

A “Four Core Genotypes” rat model to distinguish mechanisms underlying sex-biased phenotypes and diseases

Cannabidiol Improves Antioxidant Capacity and Reduces Inflammation in the Lungs of Rats with Monocrotaline-Induced Pulmonary Hypertension

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