Dataset Information

Ablation of Immunoproteasome ?5i Subunit Suppresses Hypertensive Retinopathy by Blocking ATRAP Degradation in Mice.

ABSTRACT: Inflammation is associated with retinal diseases. Our recent data demonstrate that immunoproteasome catalytic subunit ?2i contributes to angiotensin II (Ang II)-induced retinopathy in mice. Here, we investigated the role of another catalytic subunit ?5i in regulating retinopathy and its underlying mechanisms. We induced a murine model of retinopathy by infusing Ang II (3,000 ng/kg/min) for 3 weeks into wild-type (WT) mice, ?5i-knockout (KO) mice, or WT mice injected with either adenovirus-expressing ?5i (Ad-?5i) or angiotensin II type 1 receptor (AT1R)-associated protein (Ad-ATRAP), which inhibits AT1R. The ?5i expression and chymotrypsin-like activity were most significantly elevated in Ang II-infused retinas and serum from patients with hypertensive retinopathy. Moreover, Ang II infusion-induced retinopathy was markedly attenuated in ?5i-KO mice but aggravated in Ad-?5i-injected mice. Accordingly, ?5i KO markedly restored Ang II-induced downregulation of ATRAP and activation of AT1R downstream mediators, which was further enhanced in Ad-?5i-injected mice. Interestingly, overexpression of ATRAP significantly abrogated Ang II-induced retinopathy in Ad-?5i-injected mice. This study found that ?5i promoted Ang II-induced retinopathy by promoting ATRAP degradation and activation of AT1R-mediated signals.

SUBMITTER: Wang S

PROVIDER: S-EPMC6953897 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Ablation of Immunoproteasome β5i Subunit Suppresses Hypertensive Retinopathy by Blocking ATRAP Degradation in Mice.

Wang Shuai S Li Jing J Wang Tong T Bai Jie J Zhang Yun-Long YL Lin Qiu-Yue QY Li Jing-Min JM Zhao Qi Q Guo Shu-Bin SB Li Hui-Hua HH

Molecular therapy : the journal of the American Society of Gene Therapy 20191005 1

Inflammation is associated with retinal diseases. Our recent data demonstrate that immunoproteasome catalytic subunit β2i contributes to angiotensin II (Ang II)-induced retinopathy in mice. Here, we investigated the role of another catalytic subunit β5i in regulating retinopathy and its underlying mechanisms. We induced a murine model of retinopathy by infusing Ang II (3,000 ng/kg/min) for 3 weeks into wild-type (WT) mice, β5i-knockout (KO) mice, or WT mice injected with either adenovirus-expres ...[more]

PMID: 31636038

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Project description:PurposeWe investigated the association between albuminuria and hypertensive retinopathy (HR) in hypertensive adults.MethodsThis was a cross-sectional subgroup analysis of data from the China Stroke Primary Prevention Trial. We enrolled 2,964 hypertensive adults in this study. Keith-Wagener-Barker stages was used to assess HR. The urinary albumin to creatinine ratio (UACR) was calculated to evaluate albuminuria.ResultsHR was found in 76.6% (n = 2, 271) of the participants, albuminuria was found in 11.1% (n = 330). The UACR levels were significantly higher in subjects with HR than in those without HR (grade 1, β = 1.42, 95% confidence intervals [CI]: -0.12, 2.95, p = 0.070; grade 2, β = 2.62, 95% CI: 0.56, 4.67, p = 0.013; grade 3, β = 5.17, 95% CI: 1.13, 9.20, p = 0.012). In the subgroup analyses, the association between HR and UACR was stronger in current smokers (p for interaction = 0.014). The correlation between HR grades 1 and 2 and UACR was stronger in subjects with higher triglyceride levels (≥ 1.7 mmol/L), but for grade 3 HR, this correlation was stronger in subjects with lower triglycerides levels (< 1.7 mmol/L, p for interaction = 0.023). The odds of albuminuria were significantly higher in subjects with HR than in those without HR (grade 1, odds ratio [OR] = 1.57, 95% CI: 1.08, 2.29, p = 0.019; grade 2, OR = 2.02, 95% CI: 1.28, 3.18, p = 0.002; grade 3, OR = 2.12, 95% CI: 0.99, 4.55, p = 0.053). In the subgroup analyses, the association between HR grades 1 and 2 and albuminuria was stronger in subjects with higher triglycerides levels (≥ 1.7 mmol/L), but for grade 3 HR, this correlation was stronger in subjects with lower triglyceride levels (< 1.7 mmol/L, p for interaction = 0.014).ConclusionHR was positively correlated with albuminuria in hypertensive Chinese adults. This correlation was more remarkable when the population was stratified by triglycerides levels and smoking status. HR can be used as an indicator of early renal injury.

Dataset Information

Ablation of Immunoproteasome ?5i Subunit Suppresses Hypertensive Retinopathy by Blocking ATRAP Degradation in Mice.

Publications

Ablation of Immunoproteasome β5i Subunit Suppresses Hypertensive Retinopathy by Blocking ATRAP Degradation in Mice.

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