Adiponectin Deficiency Increases Allergic Airway Inflammation and Pulmonary Vascular Remodeling

Medoff, Benjamin D.; Okamoto, Yoshihisa; Leyton, Patricio; Weng, Meiqian; Sandall, Barry P.; Raher, Michael J.; Kihara, Shinji; Bloch, Kenneth D.; Libby, Peter; Luster, Andrew D.

doi:10.1165/rcmb.2008-0415oc

Cited by 184 publications

(170 citation statements)

References 88 publications

(122 reference statements)

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“…Hemodynamic Measurements in Anesthetized Closed-Chest Mice RV systolic pressure (RVSP) was measured as previously described (17). Additional information is available in the online supplement.…”

Section: Transthoracic Echocardiographymentioning

confidence: 99%

Pulmonary Hypertension after Prolonged Hypoxic Exposure in Mice with a Congenital Deficiency of Cyp2j

Beloiartsev

Rodrigues‐Machado

Zhou

et al. 2015

Am J Respir Cell Mol Biol

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Cytochrome P450 epoxygenase-derived epoxyeicosatrienoic acids contribute to the regulation of pulmonary vascular tone and hypoxic pulmonary vasoconstriction. We investigated whether the attenuated acute vasoconstrictor response to hypoxic exposure of Cyp2j 2/2 mice would protect these mice against the pulmonary vascular remodeling and hypertension associated with prolonged exposure to hypoxia. Cyp2j 2/2 and Cyp2j 1/1 male and female mice continuously breathed an inspired oxygen fraction of 0.21 (normoxia) or 0.10 (hypoxia) in a normobaric chamber for 6 weeks. We assessed hemoglobin (Hb) concentrations, right ventricular (RV) systolic pressure (RVSP), and transthoracic echocardiographic parameters (pulmonary acceleration time [PAT] and RV wall thickness). Pulmonary Cyp2c29, Cyp2c38, and sEH mRNA levels were measured in Cyp2j 2/2 and Cyp2j 1/1 male mice. At baseline, Cyp2j 2/2 and Cyp2j 1/1 mice had similar Hb levels and RVSP while breathing air. After 6 weeks of hypoxia, circulating Hb concentrations increased but did not differ between Cyp2j 2/2 and Cyp2j 1/1 mice. Chronic hypoxia increased RVSP in Cyp2j 2/2 and Cyp2j 1/1 mice of either gender. Exposure to chronic hypoxia decreased PAT and increased RV wall thickness in both genotypes and genders to a similar extent. Prolonged exposure to hypoxia produced similar levels of RV hypertrophy in both genotypes of either gender. Pulmonary Cyp2c29, Cyp2c38, and sEH mRNA levels did not differ between Cyp2j 2/2 and Cyp2j 1/1 male mice after breathing at normoxia or hypoxia for 6 weeks. These results suggest that murine Cyp2j deficiency does not attenuate the development of murine pulmonary vascular remodeling and hypertension associated with prolonged exposure to hypoxia in mice of both genders.Keywords: hypoxia; cytochrome P450 epoxygenases; pulmonary vascular remodeling; right ventricular hypertrophy Pulmonary hypertension (PH) due to increased vascular tone in lung vessels is important in many acute and chronic lung diseases, such as pulmonary embolism and idiopathic pulmonary arterial hypertension. Although progress has been made with therapeutic approaches to reduce vascular tone, all of the pathways influencing lung vascular tone have not been fully explored.

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Section: Transthoracic Echocardiographymentioning

confidence: 99%

Pulmonary Hypertension after Prolonged Hypoxic Exposure in Mice with a Congenital Deficiency of Cyp2j

Beloiartsev

Rodrigues‐Machado

Zhou

et al. 2015

Am J Respir Cell Mol Biol

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“…Explanations based solely on mechanistic effects of excessive body weight seem insufficient, as other aspects of the metabolic syndrome are also associated with impaired lung function (2). Obesity-related inflammatory markers or adipose derived hormones may influence bronchial hyperresponsiveness (BHR) as well as airway inflammation and associated tissue remodeling, as demonstrated in mouse models (3,4). But in human asthma studies, the data in favor of an effect of these circulating molecules on asthma risk remain inconclusive (5,6).…”

Section: Introductionmentioning

confidence: 99%

The Association of a Variant in the Cell Cycle Control GeneCCND1and Obesity on the Development of Asthma in the Swiss SAPALDIA Study

Thun¹,

Imboden²,

Berger³

et al. 2013

Journal of Asthma

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OBJECTIVE: The molecular mechanisms underlying the association between obesity (BMI 30 kg/m(2)) and asthma are poorly understood. Since shifts in the fate of bronchial cells due to lowgrade systemic inflammation may provide a possible explanation, we investigated whether two of the best documented functional variants in cell cycle control genes modify the obesity-asthma association. METHODS: We genotyped 5930 SAPALDIA cohort participants for the single-nucleotide polymorphisms (SNPs) rs9344 in the cyclin D1 gene (CCND1) and rs1042522 in the gene encoding tumor protein 53 (TP53). We assessed the independent association of these SNPs and obesity with asthma prevalence and incidence. RESULTS: The CCND1 SNP modified the association between obesity and asthma prevalence (p(interaction )= 0.03). The odds ratios (ORs) and 95% confidence intervals (CIs) for reporting a physician diagnosis of asthma at baseline, comparing obese with non-obese participants, were 1.09 (0.51-2.33), 1.64 (0.94-2.88), and 3.51 (1.63-7.53) for GG, GA, and AA genotypes, respectively. We found comparable genotype differences for incident asthma within the 11 years of follow-up. As for the TP53 SNP, the interactions with obesity status with respect to asthma were not statistically significant. CONCLUSIONS: Our results suggest that obesity may contribute to asthma and associated tissue remodeling by modifying the processes related to the CCND1 gene activity. Objective. The molecular mechanisms underlying the association between obesity (BMI 30 kg/m 2 ) and asthma are poorly understood. Since shifts in the fate of bronchial cells due to low-grade systemic inflammation may provide a possible explanation, we investigated whether two of the best documented functional variants in cell cycle control genes modify the obesity-asthma association. Methods. We genotyped 5930 SAPALDIA cohort participants for the single-nucleotide polymorphisms (SNPs) rs9344 in the cyclin D1 gene (CCND1) and rs1042522 in the gene encoding tumor protein 53 (TP53). We assessed the independent association of these SNPs and obesity with asthma prevalence and incidence. Results. The CCND1 SNP modified the association between obesity and asthma prevalence (p interaction ¼ 0.03). The odds ratios (ORs) and 95% confidence intervals (CIs) for reporting a physician diagnosis of asthma at baseline, comparing obese with non-obese participants, were 1.09 (0.51-2.33), 1.64 (0.94-2.88), and 3.51 (1.63-7.53) for GG, GA, and AA genotypes, respectively. We found comparable genotype differences for incident asthma within the 11 years of follow-up. As for the TP53 SNP, the interactions with obesity status with respect to asthma were not statistically significant. Conclusions. Our results suggest that obesity may contribute to asthma and associated tissue remodeling by modifying the processes related to the CCND1 gene activity.of Asthma, 2013; 50(2): 147-154 Copyright © 2013 Informa Healthcare USA, Inc. ISSN: 0277-0903 print/1532-4303

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“…This proinflammatory role of adiponectin in a mouse model of COPD-E contrasts with the well-established anti-inflammatory role of adiponectin in diabetes and atherosclerosis (6,17,19). Studies using adiponectin-deficient mice in a mouse model of ovalbumin-induced asthma have also demonstrated that such mice have increased levels of BAL eosinophils, monocytes, chemokines, and remodeling, suggesting an anti-inflammatory role for adiponectin (11). In contrast, studies in rheumatoid arthritis (5) like our studies in COPD-E suggest a proinflammatory role for adiponectin.…”

Section: Discussionmentioning

confidence: 91%

Adiponectin-deficient mice are protected against tobacco-induced inflammation and increased emphysema

Miller

Pham

Cho

et al. 2010

American Journal of Physiology-Lung Cellular and Molecular Phys

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Adiponectin Deficiency Increases Allergic Airway Inflammation and Pulmonary Vascular Remodeling

Cited by 184 publications

References 88 publications

Pulmonary Hypertension after Prolonged Hypoxic Exposure in Mice with a Congenital Deficiency of Cyp2j

Pulmonary Hypertension after Prolonged Hypoxic Exposure in Mice with a Congenital Deficiency of Cyp2j

The Association of a Variant in the Cell Cycle Control GeneCCND1and Obesity on the Development of Asthma in the Swiss SAPALDIA Study

Adiponectin-deficient mice are protected against tobacco-induced inflammation and increased emphysema

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