Glucagon-like peptide-1 (GLP-1) mediates the protective effects of dipeptidyl peptidase IV inhibition on pulmonary hypertension.
J Biomed Sci
; 26(1): 6, 2019 Jan 12.
Article
em En
| MEDLINE
| ID: mdl-30634956
ABSTRACT
BACKGROUND:
Pulmonary hypertension (PH) is a progressive disease leading to death ultimately. Our recently published data demonstrated that inhibiting dipeptidyl peptidase IV (DPP-4) alleviated pulmonary vascular remodeling in experimental PH. However, whether glucagon-like peptide-1 (GLP-1) mediated the protective effect of DPP-4 inhibition (DPP-4i) on PH is unclear.RESULTS:
In the present study, GLP-1 receptor antagonist (exendin-3) abolished the protective effects of DPP-4 inhibitor (sitagliptin) on right ventricular systolic pressure (RVSP) and pulmonary vascular remodeling (PVR) in monocrotaline (MCT, 60 mg/kg)-induced PH in rat. Notably, activation of GLP-1 receptor by GLP-1 analogue liraglutide directly attenuated RVSP and PVR in MCT-induced PH, as well as bleomycin- and chronic hypoxia-induced PH. Moreover, liraglutide potently inhibited MCT-induced inflammation and suppressed MCT-induced down-regulation of vascular endothelial marker (VE-cadherin and vWF) in lung. In vitro studies showed liraglutide reversed TGF-ß1 (5 ng/ml) combining IL-1ß (5 ng/ml) induced endothelial-mesenchymal transition (EndMT) in human umbilical vein endothelial cells (HUVECs), which could be abolished by GLP-1 receptor antagonist (exendin-3). Furtermore, liraglutide suppressed TGF-ß1-IL-1ß-induced phosphorylation of both Smad3 and ERK1/2.CONCLUSIONS:
Our data suggest that GLP-1 mediated the protective effects of DPP-4i on pulmonary vascular and RV remodeling in experimental PH, which may be attributed to the inhibitory effect on EndMT.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
6_ODS3_enfermedades_notrasmisibles
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
/
Substâncias Protetoras
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Inibidores da Dipeptidil Peptidase IV
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Incretinas
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Fosfato de Sitagliptina
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Liraglutida
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Hipertensão Pulmonar
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
J Biomed Sci
Ano de publicação:
2019
Tipo de documento:
Article