Transgelin as a potential target in the reversibility of pulmonary arterial hypertension secondary to congenital heart disease.

BACKGROUND

The reversibility of pulmonary arterial hypertension (PAH) in congenital heart disease (CHD) is of great importance for the operability of CHD. Proteomics analysis found that transgelin was significantly up-regulated in the lung tissue of CHD-PAH patients, especially in the irreversible group. However, how exactly it participated in CHD-PAH development is unknown.

METHODS

Immunohistochemical staining and Western blot were performed for further qualitative and quantitative analysis of transgelin in the lung tissues of CHD-PAH patients. The mechanism of transgelin in CHD-PAH development was explored in vitro. Primary human pulmonary arterial smooth muscle cells (hPASMCs) were cultured and infected with TAGLN siRNA or TAGLN lentiviral vector. Cell morphologic change (Coomassie Brilliant Blue staining), proliferation (cell count and EdU assay), apoptosis (terminal deoxyribonucleotidyl transferase mediated dUTP nick end labeling assay and Annexin-V flow cytometry) and migration (transwell) were evaluated following the cell treatment. The mRNA and protein expression levels were detected in real-time PCR and Western blot.

RESULTS

In line with the proteomic findings, transgelin was obviously expressed in PASMC of the middle pulmonary arterioles, especially in the irreversible PAH group. Also, transgelin expression showed positive relation with pathological grading. Experiment in vitro demonstrated that transgelin overexpression promoted PASMC proliferation and migration, strengthened cytoskeleton and was accompanied by increased expression of synthetic phenotype markers (osteopontin, proliferating cell nuclear antigen) and anti-apoptotic protein (bcl-2). On the other hand, suppression of transgelin expression activated PASMC apoptosis, reducing cell proliferation and migration.

CONCLUSIONS

Transgelin may be a potential target in the development of irreversible CHD-PAH through inducing PASMC phenotype change, proliferation, migration and reducing cell apoptosis.