Wu Min, Wu Yijin, Huang Jinsong, Wu Yueheng, Wu Hongmei, Jiang Benyuan, Zhuang Jian
Department of Cardiac Surgery, Guangdong Provincial People's Hospital, Guangzhou City, Guangdong Province, China.
PeerJ. 2020 Jan 31;8:e8153. doi: 10.7717/peerj.8153. eCollection 2020.
Pulmonary hypertension occurs in approximately 1% of the global population, and the prognosis for such patients may be poor. However, the mechanisms underlying the development of this disease remain unclear. Thus, understanding the development of pulmonary hypertension and finding new therapeutic targets and approaches are important for improved clinical outcomes.
Lung tissue specimens were collected from six patients with atrial septal defect and pulmonary hypertension (all women, with a mean age of 46.5 ± 4.7 years, and their condition could not be corrected with an internal medical occlusion device) and from nine control patients with lung cancer who underwent lobectomy (six men and three women, with a mean age of 56.7 ± 1.7 years). Isobaric tags for relative and absolute quantitation and liquid chromatography tandem mass spectrometry analyses were used to detect protein expression levels.
We found 74 significantly upregulated and 88 significantly downregulated differentially expressed proteins between control and pulmonary hypertensive lung tissue specimens. Gene ontology analyses identified the top 20 terms in all three categories, that is, biological process, cellular component, and molecular function. Kyoto Encyclopedia of Genes and Genomes and protein-protein interaction analyses determined the top 10 signaling pathways and found that the six hub proteins associated with the differentially expressed upregulated proteins (PRKAA1, DHPR, ACTB, desmin, ACTG1, and ITGA1) were all involved in hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, and dilated cardiomyopathy.
Our results identified protein expression profile changes in lung tissue derived from patients with pulmonary hypertension, providing potential new biomarkers for clinical diagnosis and prognosis for patients with pulmonary hypertension and offering candidate protein targets for future therapeutic drug development.
肺动脉高压在全球约1%的人口中出现，这类患者的预后可能较差。然而，该疾病发生发展的机制仍不清楚。因此，了解肺动脉高压的发展并找到新的治疗靶点和方法对于改善临床结局很重要。
从6例患有房间隔缺损和肺动脉高压的患者（均为女性，平均年龄46.5±4.7岁，且内科封堵装置无法纠正其病情）以及9例接受肺叶切除术的肺癌对照患者（6例男性和3例女性，平均年龄56.7±1.7岁）中收集肺组织标本。使用相对和绝对定量的等压标签以及液相色谱串联质谱分析来检测蛋白质表达水平。
我们发现对照和肺动脉高压肺组织标本之间有74种显著上调和88种显著下调的差异表达蛋白。基因本体分析确定了所有三个类别（即生物学过程、细胞成分和分子功能）中的前20个术语。京都基因与基因组百科全书和蛋白质-蛋白质相互作用分析确定了前10条信号通路，并发现与差异表达上调蛋白相关的6个枢纽蛋白（PRKAA1、DHPR、ACTB、结蛋白、ACTG1和ITGA1）均参与肥厚型心肌病、致心律失常性右室心肌病和扩张型心肌病。
我们的结果确定了肺动脉高压患者肺组织中的蛋白质表达谱变化，为肺动脉高压患者的临床诊断和预后提供了潜在的新生物标志物，并为未来治疗药物开发提供了候选蛋白质靶点。
