Pulmonary hypertension(PH) is a common complication of chronic obstructive pulmonary disease(COPD) which can worsen the prognosis and increase the mortality of COPD patients. However, the underlying mechanisms of PH in COPD(COPD-PH) remain to be elucidated. This study is the first to explore the expression profile of circRNAs in human lung tissues with definite diagnosis of COPD-PH and validate the differentially expressed circRNAs(DECs) utilizing human serum, pulmonary arterial endothelial cells(HPAECs) and pulmonary arterial smooth muscle cells(HPASMCs). A total of 136 circRNAs(39 up-regulated and 97 down-regulated) were differentially expressed between the COPD-PH group and the control group. Following quantitative real-time polymerase chain reaction(qRT-PCR) validation, two circRNAs (hsa_circ_0007608 and hsa_circ_0064656) were believed to be involved in the pathogenesis. GO and KEGG pathway analysis suggested these two DECs were mainly related to the celluar proliferation, migration and EndoMT. PPI network revealed 11 pairs of key mRNAs. VCAM1, VCAN and THBS1, three hub mRNAs with the highest reliability among all, were validated and proven to be up-regulated in COPD-PH. We innovatively found that VCAN may be involved in COPD-PH. These identified genes show high potential to be diagnostic markers and therapeutic targets of COPD-PH, and may provide new insights into the underlying mechanisms of COPD-PH patients.

The authors have declared no competing interest.

This work was supported by the Natural Science Foundations of China (82173472), the Top Talent Support Program for young and middle-aged people of Wuxi Health Committee (BJ2020006) and General Program of Wuxi Health Committee(M202032).

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the ethical review board of Wuxi People’s Hospital Affiliated to Nanjing Medical University

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