PMID- 35705467 OWN - NLM STAT- MEDLINE DCOM- 20220617 LR - 20220628 IS - 0253-3758 (Print) IS - 0253-3758 (Linking) VI - 50 IP - 6 DP - 2022 Jun 24 TI - [Gene expression signature analysis of peripheral blood mononuclear cells from patients with for high altitude pulmonary hypertension and value for potential drug selection]. PG - 577-584 LID - 10.3760/cma.j.cn112148-20220328-00215 [doi] AB - Objective: To investigate the gene expression characteristics of peripheral blood mononuclear cells from patients with high altitude pulmonary hypertension (HAPH) in Naxi residents living in Lijiang, Yunnan, and to explore the underlying pathogenesis and value for potential drug selection. Methods: This is a case-control study. Six patients with HPAH (HPAH group) and 4 normal subjects (control group) were selected from the Naxi residents who originally lived in Lijiang, Yunnan Province. The general clinical data of the two groups were collected, and the related indexes of pulmonary artery pressure were collected. Peripheral blood mononuclear cells of the subjects were collected for RNA sequencing. The differences on gene expression, regulatory network of transcription factors and drug similarity between the two groups were compared. The results were compared with the public data of idiopathic pulmonary arterial hypertension (IPAH). Biological processes and signal pathways were analyzed and compared between HPAH and IPAH patients. Results: The age of 6 patients with HAPH was (68.1+/-8.3) years old, and there were 2 males (2/6). The age of 4 subjects in the control group was (62.3+/-10.9) years old, and there were 2 males (2/4). Tricuspid regurgitation velocity, tricuspid pressure gradient and pulmonary systolic pressure in HAPH group were significantly higher than those in control group (all P<0.05). The results of RNA sequencing showed that compared with the control group, 174 genes were significantly upregulated and 169 genes were downregulated in peripheral blood mononuclear cells of HAPH group. These differentially expressed genes were associated with 220 biological processes, 52 molecular functions and 23 cell components. A total of 21 biological processes and 2 signal pathways differed between HPAH and IPAH groups, most of which were related to inflammation and immune response. ZNF384, SP1 and STAT3 were selected as highly correlated transcription factors by transcription factor prediction analysis. Trichostatin A and vorinostat were screened out as potential drugs for the treatment of HAPH by drug similarity analysis. Conclusions: There are significant differences in gene expression in peripheral blood monocytes between HAPH patients and normal population, and inflammation and immune dysfunction are the main pathogenic factors. Trichostatin A and Vorinostat are potential drugs for the treatment of HAPH. FAU - Wu, X H AU - Wu XH AD - Department of Cardiology, First Affiliated Hospital, Dali University, Dali 671000, China. FAU - Chen, Z R AU - Chen ZR AD - Department of Cardiology, First Affiliated Hospital of Guizhou Medical University, Guiyang 550001, China. FAU - He, Z Y AU - He ZY AD - Department of Cardiology, People's Hospital of Yulong, Lijiang 674100, China. FAU - Dong, Y AU - Dong Y AD - Department of Cardiology, First Affiliated Hospital, Dali University, Dali 671000, China. FAU - Yang, Y AU - Yang Y AD - Department of Cardiology, First Affiliated Hospital, Dali University, Dali 671000, China. FAU - Zhao, Q Y AU - Zhao QY AD - Department of Cardiology, First Affiliated Hospital, Dali University, Dali 671000, China. FAU - Yang, W AU - Yang W AD - Department of Cardiology, Luohe Center Hospital, Luohe 462005, China. FAU - Wang, L Y AU - Wang LY AD - Department of Cardiology, First Affiliated Hospital, Dali University, Dali 671000, China. FAU - Fu, C J AU - Fu CJ AD - Department of Cardiology, First Affiliated Hospital, Dali University, Dali 671000, China. FAU - Yang, X D AU - Yang XD AD - Department of Cardiology, First Affiliated Hospital, Dali University, Dali 671000, China. FAU - Liu, H AU - Liu H AD - Department of Cardiology, First Affiliated Hospital, Dali University, Dali 671000, China. LA - chi GR - 81560073, 81760085, 81960085/National Natural Science Foundation of China/ PT - Journal Article PL - China TA - Zhonghua Xin Xue Guan Bing Za Zhi JT - Zhonghua xin xue guan bing za zhi JID - 7910682 RN - 0 (Hydroxamic Acids) RN - 0 (Transcription Factors) RN - 3X2S926L3Z (trichostatin A) RN - 58IFB293JI (Vorinostat) RN - Pulmonary edema of mountaineers SB - IM MH - Aged MH - Altitude MH - Altitude Sickness/genetics MH - Case-Control Studies MH - China MH - Familial Primary Pulmonary Hypertension/genetics MH - Humans MH - Hydroxamic Acids/pharmacology/therapeutic use MH - *Hypertension, Pulmonary/drug therapy/genetics MH - Inflammation MH - *Leukocytes, Mononuclear/metabolism/pathology MH - Male MH - Middle Aged MH - Transcription Factors MH - *Transcriptome/genetics MH - Vorinostat/pharmacology/therapeutic use EDAT- 2022/06/16 06:00 MHDA- 2022/06/18 06:00 CRDT- 2022/06/15 22:10 PHST- 2022/06/15 22:10 [entrez] PHST- 2022/06/16 06:00 [pubmed] PHST- 2022/06/18 06:00 [medline] AID - 10.3760/cma.j.cn112148-20220328-00215 [doi] PST - ppublish SO - Zhonghua Xin Xue Guan Bing Za Zhi. 2022 Jun 24;50(6):577-584. doi: 10.3760/cma.j.cn112148-20220328-00215.