Dihydroartemisinin Attenuates Pulmonary Hypertension Through Inhibition of Pulmonary Vascular Remodeling in Rats
| Autor: | Yongpeng Zhao, Haibin Li, Jiwang Chen, Ming Tang, Ailing Li, Qian Dong, Wei Huang, Wanshi Chen, Ruiyu Wang, Panpan Feng |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty medicine.medical_treatment Myocytes Smooth Muscle Dihydroartemisinin Pulmonary Artery Vascular Remodeling 030204 cardiovascular system & hematology Muscle Smooth Vascular Rats Sprague-Dawley Neovascularization 03 medical and health sciences 0302 clinical medicine Cell Movement Fibrosis GSK-3 Internal medicine medicine.artery AXIN2 Animals Medicine Myocyte Arterial Pressure Wnt Signaling Pathway Antihypertensive Agents Cells Cultured beta Catenin Adaptor Proteins Signal Transducing Cell Proliferation Pharmacology Pulmonary Arterial Hypertension Glycogen Synthase Kinase 3 beta Monocrotaline business.industry medicine.disease Pulmonary hypertension Artemisinins Disease Models Animal 030104 developmental biology Endocrinology Pulmonary artery medicine.symptom Carrier Proteins Cardiology and Cardiovascular Medicine business |
| Zdroj: | Journal of Cardiovascular Pharmacology. 76:337-348 |
| ISSN: | 0160-2446 |
| Popis: | Pulmonary arterial hypertension (PAH) is a malignant disease characterized by pulmonary arterial remodeling because of the abnormal proliferation and migration of pulmonary arterial smooth muscle cells. Dihydroartemisinin (DHA), an artemisinin derivative used to treat malaria, is able to inhibit fibrosis, neovascularization, and tumor proliferation. In this study, we hypothesized that DHA can be beneficial in treating PAH. To test this hypothesis, a rat model of pulmonary hypertension induced with monocrotaline (MCT) was used. Compared with MCT treatment alone, treatment with 50 or 100 mg/kg DHA significantly reduced the mean pulmonary arterial pressure (30.11 ± 2.48 mm Hg vs. 21.35 ± 3.04 mm Hg and 19.18 ± 1.98 mm Hg, respectively, both P < 0.01), right ventricular transverse diameter (4.36 ± 0.41 mm vs. 3.72 ± 0.24 mm and 3.67 ± 0.27 mm, respectively, both P < 0.01), pulmonary artery medial wall thickness (57.93 ± 11.14% vs. 34.45 ± 4.39% and 25.01 ± 6.66%, respectively, both P < 0.01), and increased tricuspid annular plane systolic excursion (1.34 ± 0.17 mm vs. 1.62 ± 0.3 mm and 1.62 ± 0.16 mm, respectively, both P < 0.05). We also found that DHA inhibited platelet-derived growth factor-BB-mediated pulmonary arterial smooth muscle cells proliferation and migration in a dose-dependent manner. Moreover, DHA downregulated β-catenin levels while upregulating the levels of axis inhibition protein 2 (Axin2) and glycogen synthase kinase 3β (GSK-3β). Our findings suggest that DHA, which may be a potential candidate for PAH therapy, attenuates experimental pulmonary hypertension possibly by inhibiting pulmonary vascular remodeling. |
| Databáze: | OpenAIRE |
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