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Updated: Dec 23, 2025
The Left Pneumonectomy Combined with Monocrotaline or Sugen as a Model of Pulmonary Hypertension in Rats
Published on: March 8, 2019
Icotinib Attenuates Monocrotaline-Induced Pulmonary Hypertension by Preventing Pulmonary Arterial Smooth Muscle Cell
Li-Yao Peng1, Min Yu1, Ming-Xia Yang2
1Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, P.R. China.
Background:
Aberrant activation of epidermal growth factor receptor (EGFR) signaling pathway is associated with the pathogenesis of pulmonary hypertension (PH). However, the effect of icotinib, a first generation of EGFR tyrosine kinase inhibitor (EGFR-TKI), on PH remains to be elucidated.
Methods:
PH rat model was established by a single intraperitoneal injection of monocrotaline (MCT, 60 mg/kg). Icotinib (15, 30, and 60 mg/kg/day) was administered by oral gavage from the day of MCT injection. After 4 weeks, hemodynamic parameters and histological changes of the pulmonary arterial vessels were assessed, and the phenotypic switching of pulmonary arterial smooth muscle cells (PASMCs) was determined in vivo. Moreover, the effects of icotinib (10 µM) on epidermal growth factor (EGF, 50 ng/ml)-stimulated proliferation, migration, and phenotypic switching of human PASMCs were explored in vitro.
Results:
Icotinib significantly reduced the right ventricular systolic pressure and right ventricle hypertrophy index in rats with MCT-induced PH. Moreover, icotinib improved MCT-induced pulmonary vascular remodeling. The expression of contractile marker (smooth muscle 22 alpha (SM22α)) and synthetic markers (osteopontin (OPN) and vimentin) in pulmonary artery was restored by icotinib treatment. In vitro, icotinib suppressed EGF-induced PASMCs proliferation and migration. Meanwhile, icotinib inhibited EGF-induced downregulation of α-smooth muscle actin and SM22α and upregulation of OPN and Collagen I in PASMCs, suggesting that icotinib could inhibit EGF-induced phenotypic switching of PASMCs. Mechanistically, these effects of icotinib were associated with the inhibition of EGFR-Akt/ERK signaling pathway.
Conclusions:
Icotinib can attenuate MCT-induced pulmonary vascular remodeling and improve PH. This effect of icotinib might be attributed to preventing PASMC dysfunction by inhibiting EGFR-Akt/ERK signaling pathway.
Insights
Icotinib, an EGFR inhibitor, reduces pulmonary hypertension (PH) and vascular remodeling in rats by preventing pulmonary arterial smooth muscle cell (PASMC) dysfunction. This study highlights icotinib
Area of Science:
- Cardiovascular Research
- Pharmacology
- Cell Biology
Background:
- Aberrant epidermal growth factor receptor (EGFR) signaling drives pulmonary hypertension (PH) pathogenesis.
- The therapeutic potential of icotinib, an EGFR tyrosine kinase inhibitor (EGFR-TKI), in PH is not well understood.
Purpose of the Study:
- To investigate the efficacy of icotinib in a rat model of monocrotaline (MCT)-induced PH.
- To explore the in vitro effects of icotinib on human pulmonary arterial smooth muscle cells (PASMCs) stimulated by epidermal growth factor (EGF).
Main Methods:
- Established a rat model of PH using a single intraperitoneal injection of MCT.
- Administered icotinib orally to rats and assessed hemodynamic and histological parameters.
- Investigated the effects of icotinib on EGF-stimulated human PASMC proliferation, migration, and phenotypic switching in vitro.
Main Results:
- Icotinib significantly reduced right ventricular systolic pressure and hypertrophy in MCT-induced PH rats.
- Icotinib treatment improved pulmonary vascular remodeling and restored smooth muscle cell marker expression.
- In vitro, icotinib inhibited EGF-induced PASMC proliferation, migration, and phenotypic switching via the EGFR-Akt/ERK pathway.
Conclusions:
- Icotinib attenuates MCT-induced pulmonary vascular remodeling and ameliorates PH in rats.
- Icotinib's protective effects are linked to the inhibition of the EGFR-Akt/ERK signaling pathway, preventing PASMC dysfunction.
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