Background:
Pathobiology of pulmonary arterial hypertension (PAH) is complex. Patology and molecular biology signature during its progression is interesting to study.
Aim:
This study will describe PAH progression from first until fourth week in a model focussing on endothelin-1 (ET-1), tumor necrosis factor α (TNF-α), extracellular signal regulated kinase 1/2 (ERK1/2), intima media thickness (IMT), and proliferation of pulmonary arterial smooth muscle cells (PASMCs) and fibroblast.
Methods:
Six male Wistar rats aged 4 months old with range bodyweight of 180-230 gram were used in this experiment. Rats were injected with Monocrotaline (MCT) 60mg/kg of bodyweight (BW) subcutaneously to induce PAH. Rats were anesthesized with Ketamin 50mg/kg BW and Xylazin 5mg/kg BW intramuscularly before cathetherization. Right heart cathetherization was performed at day 1st, 2nd, 4th, 9th, 16th, and 23rd after MCT injection. After completion of cathetherization, intracardiac exsanguination was performed and blood serum was analysed by ELISA for ET-1, TNF-α, and ERK1/2. Lungs were harvested and parafinated block before analysed for IMT and proliferation of PASMCs and fibroblast.
Results:
At first until second week after MCT injection, mPAP was fluctuated. However, after 3rd until 4th week after MCT injection, its value become established over 40 mmHg. This also followed by level of ET-1 over 78 pg/mL, level of TNF-α over 223 ng/L, level of ER1/2 over 47 ng/mL, IMT over 42 µm, ratio of PASMCs over 65%, and ratio of fibroblast 30-35%.
Conclusion:
Pulmonary hypertension was established at week 3rd-4th after MCT injection in a model.
Key words: Pulmonary hypertension, Progression, Model
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