Magnesium lithospermate B ameliorates hypobaric hypoxia-induced pulmonary arterial hypertension by inhibiting endothelial-to-mesenchymal transition and its potential targets
Pulmonary arterial hypertension (PAH) is a progressive disease characterized by vascular remodeling leading to elevation of pulmonary artery pressure, right ventricular hypertrophy, and death. Currently, there are no cure exists for PAH. Magnesium lithospermate B (MLB) is the major component of Salv...
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doaj-6a61967f21394358a3cc25168b7aa1932021-05-20T07:43:18ZengElsevierBiomedicine & Pharmacotherapy0753-33222020-10-01130110560Magnesium lithospermate B ameliorates hypobaric hypoxia-induced pulmonary arterial hypertension by inhibiting endothelial-to-mesenchymal transition and its potential targetsYafeng Wang0Delong Duo1Yingjun Yan2Rongyue He3Xinan Wu4The First Hospital of Lanzhou University, Lanzhou 730000, China; Qinghai Provincial People's Hospital,Xining 810007,China; Corresponding authors at: The First Hospital of Lanzhou University, Lanzhou 730000, China.Qinghai Provincial People's Hospital,Xining 810007,ChinaQinghai Provincial People's Hospital,Xining 810007,ChinaQinghai Provincial People's Hospital,Xining 810007,ChinaThe First Hospital of Lanzhou University, Lanzhou 730000, China; Corresponding authors at: The First Hospital of Lanzhou University, Lanzhou 730000, China.Pulmonary arterial hypertension (PAH) is a progressive disease characterized by vascular remodeling leading to elevation of pulmonary artery pressure, right ventricular hypertrophy, and death. Currently, there are no cure exists for PAH. Magnesium lithospermate B (MLB) is the major component of Salvia przewalskii water extracts with treating angina and cardiovascular damage, anti-inflammation, anti-oxidation and anti-apoptosis. However, the effects of MLB on PAH still unclear. This study we investigated the efficacy of MLB in the hypobaric hypoxia-induced rat model of PAH. The results showed that MLB relieved mean pulmonary arterial pressure (mPAP) and right ventricular hypertrophy index (RVHI). Meanwhile, MLB significantly reduced pulmonary vascular remodeling. Additionally, MLB inhibited hypobaric hypoxia-induced α-smooth muscle actin (α-SMA) expression, cell apoptosis, and α-SMA and von Willebrand factor (vWF) co-expression in lung, suggesting that MLB could inhibit hypobaric hypoxia-induced endothelial-to-mesenchymal transition (EndMT). Furthermore, after treatment with MLB, the expression of hypoxia inducible factor-1α (HIF-1α), nuclear factor-kappa B (NF-κB), monocyte chemoattractant protein-1 (MCP-1), proliferating cell nuclear antigen (PCNA), cyclin-dependent kinase 4 (CDK4), CyclinD1, RhoA, rho-associated protein kinase 1 (ROCK1) and ROCK2 was decreased. Further, CHK1, PIM1, STK6, LKHA4, PDE5A, BRAF1, PLK1, AKT1, PAK6, PAK7 and ELNE may be the potential targets of MLB. Taken together, our findings suggest that MLB ameliorates hypobaric hypoxia-induced PAH by inhibiting EndMT in rats, and has potential value in the preventment and treatment of PAH.http://www.sciencedirect.com/science/article/pii/S0753332220307538Magnesium lithospermate BPulmonary arterial hypertensionEndothelial-to-mesenchymal transitionPotential targetsHypoxia |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yafeng Wang Delong Duo Yingjun Yan Rongyue He Xinan Wu |
spellingShingle |
Yafeng Wang Delong Duo Yingjun Yan Rongyue He Xinan Wu Magnesium lithospermate B ameliorates hypobaric hypoxia-induced pulmonary arterial hypertension by inhibiting endothelial-to-mesenchymal transition and its potential targets Biomedicine & Pharmacotherapy Magnesium lithospermate B Pulmonary arterial hypertension Endothelial-to-mesenchymal transition Potential targets Hypoxia |
author_facet |
Yafeng Wang Delong Duo Yingjun Yan Rongyue He Xinan Wu |
author_sort |
Yafeng Wang |
title |
Magnesium lithospermate B ameliorates hypobaric hypoxia-induced pulmonary arterial hypertension by inhibiting endothelial-to-mesenchymal transition and its potential targets |
title_short |
Magnesium lithospermate B ameliorates hypobaric hypoxia-induced pulmonary arterial hypertension by inhibiting endothelial-to-mesenchymal transition and its potential targets |
title_full |
Magnesium lithospermate B ameliorates hypobaric hypoxia-induced pulmonary arterial hypertension by inhibiting endothelial-to-mesenchymal transition and its potential targets |
title_fullStr |
Magnesium lithospermate B ameliorates hypobaric hypoxia-induced pulmonary arterial hypertension by inhibiting endothelial-to-mesenchymal transition and its potential targets |
title_full_unstemmed |
Magnesium lithospermate B ameliorates hypobaric hypoxia-induced pulmonary arterial hypertension by inhibiting endothelial-to-mesenchymal transition and its potential targets |
title_sort |
magnesium lithospermate b ameliorates hypobaric hypoxia-induced pulmonary arterial hypertension by inhibiting endothelial-to-mesenchymal transition and its potential targets |
publisher |
Elsevier |
series |
Biomedicine & Pharmacotherapy |
issn |
0753-3322 |
publishDate |
2020-10-01 |
description |
Pulmonary arterial hypertension (PAH) is a progressive disease characterized by vascular remodeling leading to elevation of pulmonary artery pressure, right ventricular hypertrophy, and death. Currently, there are no cure exists for PAH. Magnesium lithospermate B (MLB) is the major component of Salvia przewalskii water extracts with treating angina and cardiovascular damage, anti-inflammation, anti-oxidation and anti-apoptosis. However, the effects of MLB on PAH still unclear. This study we investigated the efficacy of MLB in the hypobaric hypoxia-induced rat model of PAH. The results showed that MLB relieved mean pulmonary arterial pressure (mPAP) and right ventricular hypertrophy index (RVHI). Meanwhile, MLB significantly reduced pulmonary vascular remodeling. Additionally, MLB inhibited hypobaric hypoxia-induced α-smooth muscle actin (α-SMA) expression, cell apoptosis, and α-SMA and von Willebrand factor (vWF) co-expression in lung, suggesting that MLB could inhibit hypobaric hypoxia-induced endothelial-to-mesenchymal transition (EndMT). Furthermore, after treatment with MLB, the expression of hypoxia inducible factor-1α (HIF-1α), nuclear factor-kappa B (NF-κB), monocyte chemoattractant protein-1 (MCP-1), proliferating cell nuclear antigen (PCNA), cyclin-dependent kinase 4 (CDK4), CyclinD1, RhoA, rho-associated protein kinase 1 (ROCK1) and ROCK2 was decreased. Further, CHK1, PIM1, STK6, LKHA4, PDE5A, BRAF1, PLK1, AKT1, PAK6, PAK7 and ELNE may be the potential targets of MLB. Taken together, our findings suggest that MLB ameliorates hypobaric hypoxia-induced PAH by inhibiting EndMT in rats, and has potential value in the preventment and treatment of PAH. |
topic |
Magnesium lithospermate B Pulmonary arterial hypertension Endothelial-to-mesenchymal transition Potential targets Hypoxia |
url |
http://www.sciencedirect.com/science/article/pii/S0753332220307538 |
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