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Transcriptional profiling of male and female MCT-induced rats with compensated and decompensated right ventricle

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We performed molecular phenotyping of RV remodeling, using transcriptome analysis of RV tissue obtained from MCT-induced rats (of both male and female animals). The clustering approach along with precise hemodynamics assessments identified “early" and "late" subgroups of decompensated state in rat RV. Further molecular characterization of these subgroups identified distinct molecular genes and pathways within different stages of RV remodeling. This study provided a resource to comprehensively compare human RV remodeling with the current animal model of PH (MCT), and led to validation of state-specific biomarkers and potential therapeutic targets for RV dysfunction.

本研究针对右心室重构(Right Ventricular Remodeling, RV)开展分子表型分型工作,采用野百合碱(Monocrotaline, MCT)诱导的雌雄大鼠右心室组织进行转录组分析。联合精准血流动力学评估与聚类分析方法,本研究在大鼠右心室失代偿状态中鉴定出“早期”与“晚期”两个亚组。对上述两个亚组开展进一步分子特征分析后,本研究明确了右心室重构不同阶段中具有特异性的分子基因与信号通路。本研究提供了可用于全面比较人类右心室重构与当前野百合碱诱导肺动脉高压(Pulmonary Hypertension, PH)动物模型的研究资源,并验证了针对右心室功能障碍的状态特异性生物标志物与潜在治疗靶点。

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