Osteopontin lung gene expression is a marker of disease severity in pulmonary arterial hypertension

Abstract

Background and objective: Osteopontin (OPN) is a pleiotropic cytokine involved in the proliferation of pulmonary artery smooth muscle cells (PA-SMC). OPN is upregulated in the lungs of patients with pulmonary hypertension (PH) associated with pulmonary fibrosis, suggesting that the lung is a source of OPN. We hypothesized that OPN lung expression is elevated in Group I pulmonary arterial hypertension (PAH) and is correlated to haemodynamics. Methods: Microarray analysis (Affymetrix) was performed after RNA was extracted from explanted lungs in 15 patients with Group I PAH who underwent lung transplantation (LTx) and 11 normal controls. PA pressure levels were recorded intraoperatively, immediately before starting LTx. Serum OPN levels were measured in subjects with PAH, Group II PH and normal controls on the day of right heart catheterization. Results: OPN was among the top five upregulated genes in PAH compared to normal controls, which was confirmed by reverse transcription polymerase chain reaction (RT-PCR). OPN expression was similar and equally elevated in different subtypes of PAH. A strong significant correlation was observed between mean pulmonary arterial pressure and OPN gene expression. Ingenuity pathway analysis showed the involvement of OPN in functions and networks relevant to angiogenesis, cell death and proliferation of PA-SMC. OPN serum levels did not differ in subjects with Group I PAH and Group II PH. Conclusion: In the lungs of patients with severe PAH, OPN is highly expressed and the level of expression is significantly correlated to disease severity. OPN may play an important role in the vascular remodelling process of PAH. SUMMARY AT A GLANCEOsteopontin (OPN), a pleiotropic cytokine, was identified among the top five upregulated genes in the lung explants from patients with Group I pulmonary arterial hypertension, compared to normal controls. Its expression correlated strongly to haemodynamic severity. Ingenuity pathway analysis showed the involvement of OPN in functions and networks relevant to vascular remodelling.

Cannabidiol Attenuates Pulmonary Arterial Hypertension by Normalizing the Mitochondrial Function in Vascular Smooth Muscle Cells

“…We found that CBD treatment reduced the hypoxia-increased glycolysis in human PASMCs (Figure S5E-F). To verify our findings of the glycolysis in vitro and in vivo, we downloaded and re-analyzed the gene expression data of patients with PAH from the public database (No.GSE113439) [37], we obtained the increased expression of pyruvate dehydrogenase lipoamide kinase isozyme 1 ( PDK1 , a key enzyme in glycolysis) in the lung from 15 PAH patients (Figure 6C). Additionally, we observed that CBD significantly reduced the expression level of PDK1 , which was elevated in hypoxia-induced human PASMCs (Figure 6D).…”

Screening of Hub Genes Associated with Pulmonary Arterial Hypertension by Integrated Bioinformatic Analysis

“…It has been reported that SPP1 plays a role in PAH via enhancing pulmonary vascular smooth muscle cell (PVSMC) proliferation [50,51]. The expression level of SPP1 was related to the severity of PAH [52,53]. These results suggest that SPP1 may be a prognostic indicator and therapeutic target for PAH.…”

Transcriptomic analysis identifies Toll‐like and Nod‐like pathways and necroptosis in pulmonary arterial hypertension

“…Interestingly, Rela has been demonstrated to be the specific member of the NF‐kB family linked to pulmonary vascular remodelling 29 . Of this inflammatory and immune profiling, it is noteworthy that several inflammatory factors including CCL2, 30 SELP, 31 SPP1, 32 IL17, 33 IL1B, 2 IL12A, 2 ADA 34 and PF4 35 have already been demonstrated to be associated with pulmonary vascular remodelling/pulmonary hypertension.…”