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Dipeptidyl peptidase IV (DPP-4) inhibition alleviates pulmonary arterial remodeling in experimental pulmonary hypertension

Dipeptidyl peptidase IV (DPP-4) is well known for its role in glucose homeostasis, and DPP-4 inhibitor (DPP-4i) exhibits multiple actions in cardiovascular diseases. However, the effect of DPP-4i on pulmonary hypertension (PH) remains unclear. Therefore, this study aims to investigate the effect of DPP-4i on pulmonary arterial remodeling in rats with PH and the potential underlying mechanisms. Our results show that DPP-4 was expressed in epithelial cells, endothelial cells, smooth muscle cells, and inflammatory cells in lung. DPP-4i (Sitagliptin) attenuated right ventricular systolic pressure (RVSP), right ventricle remodeling, hypertrophy of pulmonary arterial medial layer, inflammatory cell infiltration, and endothelial–mesenchymal transition (EndMT) in monocrotaline (MCT)-induced PH rats. Similarly, DPP-4i also alleviated bleomycin- and chronic hypoxia-induced PH in rats. In cultured human pulmonary arterial smooth muscle cells (PASMCs), DPP-4i inhibited platelet derived growth factor (PDGF)-BB-induced proliferation and migration, which was abolished by phosphatase and tensin homolog deleted on chromosome ten (PTEN) knockout. These results demonstrate that DPP-4 inhibition alleviates pulmonary arterial remodeling in experimental PH by inhibiting proliferation and migration of PASMCs.

Autoren:   Jian Xu; Jingjing Wang; Mengyu He; Honghao Han; Weiping Xie; Hong Wang; Hui Kong
Journal:   Laboratory Investigation
Jahrgang:   2018
Seiten:   1
DOI:   10.1038/s41374-018-0080-1
Erscheinungsdatum:   22.05.2018
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