Our primary findings were as follows: (1) We identified 2953 proteins, including 74 significantly upregulated DEPs and 88 significantly downregulated DEPs, between control and pulmonary hypertensive lung tissues; (2) GO analysis elucidated the top 20 terms associated with categories of biological process, cellular component, and molecular function; (3) KEGG and PPI analyses identified the top 10 signaling pathways and six hub proteins, including PRKAA1, DHPR, ACTB, desmin, ACTG1 and ITGA1. Here, ACTG1 is linked to pulmonary hypertension.