An integrated proteomic and transcriptomic signature of the failing right ventricle in monocrotaline induced pulmonary arterial hypertension in male rats.
An integrated proteomic and transcriptomic signature of the failing right ventricle in monocrotaline induced pulmonary arterial hypertension in male rats.
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DOI：
10.3389/fphys.2022.966454
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发表时间：
2022
影响因子：
4
通讯作者：
中科院分区：
文献类型：
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目的：肺动脉高压(PAH)是一种可导致右心衰竭(RVF)死亡的阻塞性肺血管病变。目前对RVF在PAH中的分子机制了解有限。方法：在成年雄性大鼠注射野百合碱(MCT；60 mg/kg)建立的PAH-RVF模型上，用质谱仪鉴定PAH诱导的RVF后RV内蛋白质的变化。生物信息学分析被用来整合我们之前发表的来自PAH大鼠独立队列的RNA测序数据。结果：与对照组相比，我们在MCT大鼠的RV中鉴定出1,277个差异调节蛋白。整合MCT、RV转录组和蛋白质组数据集确定了410个在mRNA和蛋白质水平上受到一致调控的靶点。对这些数据的功能分析显示了丰富的功能，包括线粒体代谢、细胞呼吸和嘌呤代谢。我们还优先选择了15个高度浓缩的蛋白质：转录本对，并确认了它们作为RVF贡献者的生物学合理性。我们使用多种PAH模型，包括雄性SU5416-缺氧模型和几个雄性大鼠品系，证明了这些差异表达对与独立研究人员发表的数据重叠。结论：多组整合为研究PAH中RVF的分子表型提供了一个新的视角，该表型包括涉及嘌呤代谢、线粒体功能、炎症和纤维化的通路的失调。
Aim: Pulmonary arterial hypertension (PAH) is an obstructive pulmonary vasculopathy that results in death from right ventricular failure (RVF). There is limited understanding of the molecular mechanisms of RVF in PAH. Methods: In a PAH-RVF model induced by injection of adult male rats with monocrotaline (MCT; 60 mg/kg), we performed mass spectrometry to identify proteins that change in the RV as a consequence of PAH induced RVF. Bioinformatic analysis was used to integrate our previously published RNA sequencing data from an independent cohort of PAH rats. Results: We identified 1,277 differentially regulated proteins in the RV of MCT rats compared to controls. Integration of MCT RV transcriptome and proteome data sets identified 410 targets that are concordantly regulated at the mRNA and protein levels. Functional analysis of these data revealed enriched functions, including mitochondrial metabolism, cellular respiration, and purine metabolism. We also prioritized 15 highly enriched protein:transcript pairs and confirmed their biological plausibility as contributors to RVF. We demonstrated an overlap of these differentially expressed pairs with data published by independent investigators using multiple PAH models, including the male SU5416-hypoxia model and several male rat strains. Conclusion: Multiomic integration provides a novel view of the molecular phenotype of RVF in PAH which includes dysregulation of pathways involving purine metabolism, mitochondrial function, inflammation, and fibrosis.
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影响因子：
5
作者：
Gabrielsen, Anders;Lawler, Patrick R.;Hansson, Goran K.
通讯作者：
Hansson, Goran K.
DOI：
10.1073/pnas.78.11.6858
发表时间：
1981-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
AMES, BN;CATHCART, R;HOCHSTEIN, P
通讯作者：
HOCHSTEIN, P
影响因子：
3.7
作者：
Allwood, Melissa A.;Kinobe, Robert T.;Simpson, Jeremy A.
通讯作者：
Simpson, Jeremy A.
影响因子：
9.6
作者：
Chemla, D;Castelain, V;Hervé, P
通讯作者：
Hervé, P
影响因子：
3.7
作者：
Charif M;Roubertie A;Salime S;Mamouni S;Goizet C;Hamel CP;Lenaers G
通讯作者：
Lenaers G