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Updated: Jun 2, 2026
The Left Pneumonectomy Combined with Monocrotaline or Sugen as a Model of Pulmonary Hypertension in Rats
Published on: March 8, 2019
Involvement of mast cells in monocrotaline-induced pulmonary hypertension in rats
Bhola K Dahal1, Djuro Kosanovic, Christina Kaulen
1University of Giessen Lung Centre, Giessen, Germany.
Background:
Mast cells (MCs) are implicated in inflammation and tissue remodeling. Accumulation of lung MCs is described in pulmonary hypertension (PH); however, whether MC degranulation and c-kit, a tyrosine kinase receptor critically involved in MC biology, contribute to the pathogenesis and progression of PH has not been fully explored.
Methods:
Pulmonary MCs of idiopathic pulmonary arterial hypertension (IPAH) patients and monocrotaline-injected rats (MCT-rats) were examined by histochemistry and morphometry. Effects of the specific c-kit inhibitor PLX and MC stabilizer cromolyn sodium salt (CSS) were investigated in MCT-rats both by the preventive and therapeutic approaches. Hemodynamic and right ventricular hypertrophy measurements, pulmonary vascular morphometry and analysis of pulmonary MC localization/counts/activation were performed in animal model studies.
Results:
There was a prevalence of pulmonary MCs in IPAH patients and MCT-rats as compared to the donors and healthy rats, respectively. Notably, the perivascular MCs were increased and a majority of them were degranulated in lungs of IPAH patients and MCT-rats (p < 0.05 versus donor and control, respectively). In MCT-rats, the pharmacological inhibitions of MC degranulation and c-kit with CSS and PLX, respectively by a preventive approach (treatment from day 1 to 21 of MCT-injection) significantly attenuated right ventricular systolic pressure (RVSP) and right ventricular hypertrophy (RVH). Moreover, vascular remodeling, as evident from the significantly decreased muscularization and medial wall thickness of distal pulmonary vessels, was improved. However, treatments with CSS and PLX by a therapeutic approach (from day 21 to 35 of MCT-injection) neither improved hemodynamics and RVH nor vascular remodeling.
Conclusions:
The accumulation and activation of perivascular MCs in the lungs are the histopathological features present in clinical (IPAH patients) and experimental (MCT-rats) PH. Moreover, the accumulation and activation of MCs in the lungs contribute to the development of PH in MCT-rats. Our findings reveal an important pathophysiological insight into the role of MCs in the pathogenesis of PH in MCT-rats.
Insights
Mast cells (MCs) accumulate and activate in pulmonary hypertension (PH). Inhibiting MCs early in PH development in rats improved lung function and vascular remodeling, but not when treatment started later.
Area of Science:
- Pulmonary Medicine
- Immunology
- Pathophysiology
Background:
- Mast cells (MCs) are involved in inflammation and tissue remodeling.
- Increased lung MCs are observed in pulmonary hypertension (PH).
- The role of MC degranulation and c-kit in PH pathogenesis is under-explored.
Purpose of the Study:
- To investigate the contribution of MC degranulation and c-kit to PH pathogenesis.
- To evaluate the therapeutic potential of targeting MCs in PH.
Main Methods:
- Examined pulmonary MCs in idiopathic pulmonary arterial hypertension (IPAH) patients and monocrotaline-induced PH rats (MCT-rats).
- Assessed the effects of c-kit inhibitor (PLX) and MC stabilizer (CSS) in MCT-rats using preventive and therapeutic treatment strategies.
- Measured hemodynamic parameters, right ventricular hypertrophy, and pulmonary vascular remodeling.
Main Results:
- Pulmonary MCs, particularly perivascular ones, were increased and degranulated in IPAH patients and MCT-rats.
- Preventive treatment with CSS and PLX significantly reduced right ventricular systolic pressure, hypertrophy, and vascular remodeling in MCT-rats.
- Therapeutic treatment with CSS and PLX did not improve hemodynamics, hypertrophy, or vascular remodeling in later stages of PH in MCT-rats.
Conclusions:
- Perivascular MC accumulation and activation are key features in PH.
- Early intervention targeting MCs and c-kit can ameliorate PH development in a rat model.
- The timing of MC-targeted therapy is crucial for efficacy in PH treatment.
