Dehydroabietic Acid Isolated from Commiphora opobalsamum Causes Endothelium-Dependent Relaxation of Pulmonary Artery via PI3K/Akt-eNOS Signaling Pathway

Gao, Wenyan; Dong, Xiaoyan; Xie, Nan; Zhou, Chunlan; Fan, Yuhua; Chen, Guoyou; Wang, Yanming; Wei, Taiming; Zhu, Daling

doi:10.3390/molecules19068503

Cited by 13 publications

(7 citation statements)

References 30 publications

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“…22,23 Inhibition of the PI3K/Akt/eNOS pathway was also an important instigator in pulmonary artery endothelial dysfunction. [24][25][26] Besides, several very recent studies have showed that the PI3K/Akt pathway negatively regulated MMP-2 secretion in several types of cells, including vascular smooth muscle cells, hepatocellular carcinoma cells, and glioblastoma cells. [27][28][29] The activation of the PI3K/Akt pathway caused upregulation of Forkhead Box O3 (FoxO3a), a famous tumor suppressor, and suppressed MMP-2 expression to inhibit the migration vascular smooth muscle cells.…”

Section: Discussionmentioning

confidence: 99%

CTRP9 Ameliorates Pulmonary Arterial Hypertension Through Attenuating Inflammation and Improving Endothelial Cell Survival and Function

Xu²,

Wang³

et al. 2016

Journal of Cardiovascular Pharmacology

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Endothelial dysfunction and inflammation are believed to be 2 primary instigators of pulmonary arterial hypertension (PH). C1q/TNF-related protein 9 (CTRP9) plays important roles in anti-inflammation and improvement of epithelial function. However, the role of CTRP9 in the progression of PH remains still unclear. In this study, the role and mechanism of CTRP9 in the PH progression were explored. First, serum CTRP9 contents and CTRP9 mRNA expression in the pulmonary artery epithelial cells from patients with PH were detected. Our data on enzyme-linked immunosorbent assay and real-time quantitative Polymerase Chain Reaction showed that CTRP9 mRNA and protein content were markedly downregulated in the patients with PH. Then the pcDNA-CTRP9 expression vector or CTRP9 siRNA was transfected into the primary pulmonary artery epithelial cells from the patients with PH in vitro. CTRP9 overexpression significantly improved endothelial NOS protein expression and reduced the secretion of endothelin-1 (ET-1) and matrix metalloproteinase-2 (MMP-2), whereas knockdown of CTRP9 sharply reduced eNOS protein expression and promoted the secretion of ET-1 and MMP-2 in the cultured human epithelial cells. Moreover, the levels of phosphatidylinositol 3-kinase (PI3K) and pAkt were reduced in the epithelial cells and CTRP9 overexpression activated the PI3K/Akt pathway. CTRP9 could inhibit cell apoptosis and eNOS expression reduction in the cells pretreated with the PI3K/Akt inhibitor LY294002 and resist LY294002-induced ET-1 and MMP-2 secretion. Finally, to verify the role of CTRP9 in the progression of PH in vivo, the pcDNA-CTRP9 expression vector or CTRP9 siRNA was intravenously injected into rats with PH. Pulmonary arterial pressures of the rats were notably reduced by the pcDNA-CTRP9 injection and elevated by the CTRP9 siRNA injection. In conclusion, CTRP9 ameliorated PH by attenuating inflammation and improving endothelial cell survival and function.

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Section: Discussionmentioning

confidence: 99%

CTRP9 Ameliorates Pulmonary Arterial Hypertension Through Attenuating Inflammation and Improving Endothelial Cell Survival and Function

Xu²,

Wang³

et al. 2016

Journal of Cardiovascular Pharmacology

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“…), opened the thoraxes and quickly detached the lungs, which were further processed for immunocytochemistry. At the end of the 9-day exposure period, we anesthetized and dissected each rat as previously described [ 20 ].…”

Section: Methodsmentioning

confidence: 99%

Key Role of ROS in the Process of 15-Lipoxygenase/15-Hydroxyeicosatetraenoiccid-Induced Pulmonary Vascular Remodeling in Hypoxia Pulmonary Hypertension

Mao

Qiu

et al. 2016

PLoS ONE

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We previously reported that 15-lipoxygenase (15-LO) and its metabolite 15-hydroxyeicosatetraenoic acid (15-HETE) were up-regulated in pulmonary arterial cells from both pulmonary artery hypertension patients and hypoxic rats and that these factors mediated the progression of pulmonary hypertension (PH) by affecting the proliferation and apoptosis of pulmonary arterial (PA) cells. However, the underlying mechanisms of the remodeling induced by 15-HETE have remained unclear. As reactive oxygen species (ROS) and 15-LO are both induced by hypoxia, it is possible that ROS are involved in the events of hypoxia-induced 15-LO expression that lead to PH. We employed immunohistochemistry, tube formation assays, bromodeoxyuridine (BrdU) incorporation assays, and cell cycle analyses to explore the role of ROS in the process of 15-HETE-mediated hypoxic pulmonary hypertension (HPH). We found that exogenous 15-HETE facilitated the generation of ROS and that this effect was mainly localized to mitochondria. In particular, the mitochondrial electron transport chain and nicotinamide-adenine dinucleotide phosphate oxidase 4 (Nox4) were responsible for the significant 15-HETE-stimulated increase in ROS production. Moreover, ROS induced by 15-HETE stimulated endothelial cell (EC) migration and promoted pulmonary artery smooth muscle cell (PASMC) proliferation under hypoxia via the p38 MAPK pathway. These results indicated that 15-HETE-regulated ROS mediated hypoxia-induced pulmonary vascular remodeling (PVR) via the p38 MAPK pathway.

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“…The first possibility we considered was contribution from nitric oxide (NO) signaling pathway. It is well known that NO mainly from the endothelium in vascular systems, and plays critical roles in vascular relaxation [21] [22]. Damage of vascular endothelium or NO pathways may cause disability of vascular functions, particularly vasodilation [23]- [26].…”

Section: Discussionmentioning

confidence: 99%

Shengmai Suppressed Vascular Tension in Umbilical Arteries and Veins of Human and Sheep

Yin¹,

Gu²,

He³

et al. 2015

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Objective-The umbilical cord is a critical pathway between mothers and fetuses, and regulations of umbilical vessel tension are important for fetal growth. Shengmai is an herbal medicine being used in treatments of cardiovascular diseases. However, effects of Shengmai on human blood vessels and related pharmacological mechanisms are unclear. Methods-This study investigated the effects of related mechanisms of Shengmai and its key compounds on human and sheep umbilical arteries and veins using organ bath systems. Key Findings-Shengmai significantly suppressed phenylephrine-stimulated vasoconstriction in umbilical arteries and veins. NG-Nitro-L-arginine Methyl Estercould not change the Shengmai-suppressed vasoconstriction in human and sheep umbilical vessels. Among four key compounds of Shengmai, Ginsenoside Re, Ginsenoside Rb1, Ginsenoside Rg1, and Schisandrin, only Ginsenoside Re showed the significant effect similar to Shengmai's in the umbilical vessels. In Ca 2+-free solution, Ginsenoside Re did not affect vasoconstriction. In addition, caffeine-or phenylephrine-stimulated vasoconstriction were not changed by Ginsenoside Re. Either charybdotoxin or glibenclamide could inhibit Ginsenoside Re-caused inhibition of the stimulated vasoconstriction in both human and sheep umbilical vessels, where 4-aminopyridine did not show the similar inhibitory effect. Conclusion-The results provide new information on Shengmai's effects and underlying mechanisms in umbilical vessels. Importantly, the information gained offers interesting potential for developing new drugs acting on umbilical cords for fetal medicine.

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Dehydroabietic Acid Isolated from Commiphora opobalsamum Causes Endothelium-Dependent Relaxation of Pulmonary Artery via PI3K/Akt-eNOS Signaling Pathway

Cited by 13 publications

References 30 publications

CTRP9 Ameliorates Pulmonary Arterial Hypertension Through Attenuating Inflammation and Improving Endothelial Cell Survival and Function

CTRP9 Ameliorates Pulmonary Arterial Hypertension Through Attenuating Inflammation and Improving Endothelial Cell Survival and Function

Key Role of ROS in the Process of 15-Lipoxygenase/15-Hydroxyeicosatetraenoiccid-Induced Pulmonary Vascular Remodeling in Hypoxia Pulmonary Hypertension

Shengmai Suppressed Vascular Tension in Umbilical Arteries and Veins of Human and Sheep

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