Novel insights into the molecular mechanisms underlying the beneficial effects of exercise training on pulmonary arterial hypertension.

Abstract

Recent animal and clinical studies report that exercise training exerts positive influences in pulmonary arterial hypertension (PAH); however, the underlying mechanisms are largely unknown. To give insight into the molecular mechanisms of the improvement effects, we performed gene expression analysis. Three Gene Expression Omnibus (GEO) datasets were analyzed, including peripheral blood mononuclear (PBMC) gene expression profiles of exercise training in men and patients with PAH. Differentially expressed genes (DEGs) in each dataset were identified, and then, the common DEGs positively regulated by PAH and negatively regulated by exercise training, or the opposite, were further identified. Subsequently, biological processes and pathways were analyzed. A total of 7229 DEGs with logFC>0.3 and P<0.05 were identified in exercise, whereas 749 and 2207 DEGs were identified in PAH from the two datasets. After overlapping the whole DEGs from all three datasets, total 16 common DEGs were identified, including BCLAF1, SATB1 and ZFP36L2. Seven of them were up-regulated in exercise training and down-regulated in PAH, and the others were opposite. In addition, these common DEGs were mainly enriched in negative regulation of cellular process, negative regulation of biological process and negative regulation of cellular macromolecule biosynthetic process. Some genes have been implicated in the improvement of pulmonary vascular remodeling and PAH. These findings could not only improve the knowledge about the molecular mechanisms underlying the beneficial effects of exercise training on PAH, but also provide clues for further clinical and animal studies.