Galectin-3 aggravates pulmonary arterial hypertension via immunomodulation in congenital heart disease.

Pulmonary arterial hypertension (PAH) is reported to contribute to right ventricular failure and death. PAH of variable degrees is often related to congenital heart disease (CHD). Galectin-3 (Gal-3) has been proven to be of great importance in PAH and CHD. Therefore, we investigated the specific mechanism of Gal-3 in CHD-PAH. Patients with CHD-PAH were enrolled to detect the changes of T-cell subsets, cytokine levels, and other related inflammatory cells in the plasma and to assess the Gal-3 levels in the serum. Next, CHD-PAH mouse models were established and treated with restored or depleted Gal-3 to evaluate the systolic pulmonary artery pressure (sPAP) and right ventricular hypertrophy index (RVHI), to determine levels of IL-4, IL-5, IL-13, AKT and p-AKT along with proliferation of pulmonary artery smooth muscle cells (PASMCs). Finally, we explored the effects of adoptive transfer of CD4+T cells on CHD-PAH in mice with Gal-3 knockdown to further investigate the role of Gal-3 in vivo. Initially, Gal-3 was up-regulated in patients with CHD-PAH. Subsequently, it was demonstrated that restored Gal-3 increased sPAP and RVHI, and promoted proliferation of PASMCs by activating the immune response with elevated levels of IL-4, IL-5, IL-13 and p-AKT. Finally, adoptive transfer of CD4+T cells promoted CD4+T cell perivascular infiltration and the progression of CHD-PAH in mice with Gal-3 knockdown. Collectively, the current study suggests a facilitating role of Gal-3 in pulmonary artery remodeling and progression of CHD-PAH via activation of Th2.