Tirofiban induces vasorelaxation of the coronary artery via an endothelium-dependent NO-cGMP signaling by activating the PI3K/Akt/eNOS pathway

Xia, Tianyang; Guan, Weiwei; Fu, Jinjuan; Zou, Xingxing; Han, Yu; Chen, Caiyu; Zhou, Lin; Zeng, Chunyu; Wang, Wei Eric

doi:10.1016/j.bbrc.2016.03.110

Cited by 18 publications

(10 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, miR-138 was reported to contribute to endothelial cell dysfunction when induced by pro-inflammatory cytokines [3]. Additionally, the biological activities of endothelial cells, such as HCAECs, are associated with the phosphatidylinositol 3-kinase/protein kinase B/endothelial NO synthase (PI3K/Akt/eNOS) signalling pathway [11][12][13]. Ou et al [14] reported that the PI3K/Akt/ eNOS/NO pathway plays a role in OX-LDL-induced endothelial apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Overexpression of microRNA‐138 alleviates human coronary artery endothelial cell injury and inflammatory response by inhibiting the PI3K/Akt/eNOS pathway

Wang

Yao

et al. 2017

J Cellular Molecular Medi

View full text Add to dashboard Cite

This study aimed to investigate the role of miR‐138 in human coronary artery endothelial cell (HCAEC) injury and inflammatory response and the involvement of the PI3K/Akt/eNOS signalling pathway. Oxidized low‐density lipoprotein (OX‐LDL)‐induced HCAEC injury models were established and assigned to blank, miR‐138 mimic, miR‐138 inhibitor, LY294002 (an inhibitor of the PI3K/Akt/eNOS pathway), miR‐138 inhibitor + LY294002 and negative control (NC) groups. qRT‐PCR and Western blotting were performed to detect the miR‐138, PI3K, Akt and eNOS levels and the protein expressions of PI3K, Akt, eNOS, p‐Akt, p‐eNOS, Bcl‐2, Bax and caspase‐3. ELISAs were employed to measure the expressions of TNF‐α, IL‐4, IL‐6, IL‐8, IL‐10 and nitric oxide (NO) and the activities of lactate dehydrogenase (LDH) and eNOS. MTT and flow cytometry were performed to assess the proliferation and apoptosis of HCAECs. Compared to the blank group, PI3K, Akt and eNOS were down‐regulated in the miR‐138 mimic and LY294002 groups but were up‐regulated in the miR‐138 inhibitor group. The miR‐138 mimic and LY294002 groups showed decreased concentrations of TNF‐α, IL‐6, IL‐8 and NO and reduced activities of LDH and eNOS, while opposite trends were observed in the miR‐138 inhibitor group. The concentrations of IL‐4 and IL‐10 increased in the miR‐138 mimic and LY294002 groups but decreased in the miR‐138 inhibitor group. The miR‐138 mimic and LY294002 groups had significantly decreased cell proliferation and increased cell apoptosis compared to the blank group. These findings indicate that up‐regulation of miR‐138 alleviates HCAEC injury and inflammatory response by inhibiting the PI3K/Akt/eNOS signalling pathway.

show abstract

Section: Introductionmentioning

confidence: 99%

Overexpression of microRNA‐138 alleviates human coronary artery endothelial cell injury and inflammatory response by inhibiting the PI3K/Akt/eNOS pathway

Wang

Yao

et al. 2017

J Cellular Molecular Medi

View full text Add to dashboard Cite

show abstract

“…NO synthesis, which is regulated by eNOS in endothelial cells, is closely connected to vasodilation related to blood pressure [44]. It has been reported that NO released by HUVECs activates sGC, which is a NO receptor in SMC, thereby converting GTP to cGMP, and this activation can lead to vascular relaxation [24, 45]. To elucidate the effect of LA on the phosphorylation of eNOS, which is a protein involved in NO production, HUVECs were treated with LA (15 μM) and L-NAME (25 μM).…”

Section: Discussionmentioning

confidence: 99%

“…Synthesized NO stimulates soluble guanylyl cyclase (sGC), which is a receptor for NO in smooth muscle cells (SMC), thereby converting guanosine triphosphate (GTP) to cyclic guanosine monophosphate (cGMP) [23]. Activation of sGC leads to vascular relaxation via NO-cGMP signaling [24]. These endothelial functional effects of saponin from ginseng, such as ginsenoside-Rg1, on NO production via the PI3K/Akt/eNOS signaling pathway in HUVECs are well known [25, 26].…”

Section: Introductionmentioning

confidence: 99%

Lancemaside A, a major triterpene saponin of Codonopsis lanceolata enhances regulation of nitric oxide synthesis via eNOS activation

Lee

Kim

et al. 2019

BMC Complement Altern Med

View full text Add to dashboard Cite

Background Many studies on the effect of saponin-rich Codonopsis lanceolata as a bioactive source for improving physical health have been performed. C. lanceolata contains triterpenoid saponins, including lancemasides. These saponins are known to be particularly involved in the regulation of blood pressure or hypertension. This study investigated whether lancemaside A (LA), a major triterpenoid saponin from C. lanceolata , regulates nitric oxide (NO) production via the activation of endothelial NO synthase (eNOS) in human umbilical vein endothelial cells. Methods Upon separation with petroleum ether, ethyl acetate, and n -butanol, LA was found to be abundant in the n -butanol-soluble portion. For further purification of LA, HPLC was performed to collect fraction, and LA was identified using analysis of LC/MSMS and 13 C-NMR values. In in vitro, the effects of LA on NO release mechanism in HUVECs were investigated by Griess assay, quantitative real-time reverse-transcription PCR, and Western blotting. Results Our results showed that NO production was efficiently improved by treatment with LA in a dose-dependent manner. In addition, the LA treatment resulted in extensive recovery of the NO production suppressed by the eNOS inhibitor, L-NAME, compared with that in the control group. Additionally, the level of eNOS mRNA was increased by this treatment in a dose-dependent manner. These results suggested that LA is an inducer of NO synthesis via eNOS mRNA expression. Also, the study indicated that LA is involved in activating the PI3K/Akt/eNOS signaling pathway. Conclusion These results suggested that LA is an inducer of NO synthesis via eNOS mRNA expression. Also, the study indicated that LA is involved in activating the PI3K/Akt/eNOS signaling pathway. These findings suggest the value of using LA as a component of functional foods and natural pharmaceuticals. Electronic supplementary material The online version of this article (10.1186/s12906-019-2516-6) contains supplementary material, which is available to authorized users.

show abstract

“…The functional removed endothelium was also incubated with AGIV (10 -6 -10 -1 mM). The contractile responses of the segments were measured by the AcqKnowledge v4.1 software system (BIOPAC USA) [21,31]. The animals in our research received humane care in compliance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals.…”

Section: Preparation Of Aortic Rings and Vasodilatation Studymentioning

confidence: 99%

Astragaloside IV Improves Vasodilatation Function by Regulating the PI3K/Akt/eNOS Signaling Pathway in Rat Aorta Endothelial Cells

et al. 2018

View full text Add to dashboard Cite

Coronary heart disease (CHD) remains a major public health burden. Endothelial-dependent coronary artery vasoreactivity is a significant indicator of vascular function. Endothelial dysfunction is characterized by decreased nitric oxide (NO) bioavailability and predicts late cardiovascular events. Astragaloside IV (AGIV) is the main active component of the herb Astragalus membranaceus. Although it shows a significant protective effect against vascular endothelial dysfunction, the mechanisms of AGIV promoting the vascular dilation have not been elucidated. This study investigated the vasodilator effect of AGIV on rat aortic rings and the underlying effect of AGIV via the PI3K/Akt/eNOS signaling pathway. We measured the relaxation of isolated RARs after different concentrations of AGIV treatment. Rat aorta endothelial cells were cultured with different doses of AGIV, dimethylsulfoxide, and NG-nitro L-arginine methyl ester. The expression of phosphorylated (p)-Akt and -endothelial nitric oxide synthase (p-eNOS) were tested by Western blot analysis. The messenger (m)RNA expression of eNOS was quantified by real-time polymerase chain reaction. AGIV exerted a vasodilator effect on the aortic rings and increased the NO content in a concentration-dependent manner. The vasorelaxation was suppressed by an eNOS inhibitor. AGIV regulated the PI3K/Akt/eNOS signaling pathway via phosphorylation of Akt at Ser⁴⁷³ and dephosphorylation of eNOS at Thr⁴⁹⁵. The mRNA expression of eNOS was remarkably upregulated by AGIV. AGIV significantly induced the dilation of the aortic rings, leading to the vasodilator response by enhancing the eNOS release via the PI3K/Akt/eNOS signaling pathway.

show abstract

Tirofiban induces vasorelaxation of the coronary artery via an endothelium-dependent NO-cGMP signaling by activating the PI3K/Akt/eNOS pathway

Cited by 18 publications

References 34 publications

Overexpression of microRNA‐138 alleviates human coronary artery endothelial cell injury and inflammatory response by inhibiting the PI3K/Akt/eNOS pathway

Overexpression of microRNA‐138 alleviates human coronary artery endothelial cell injury and inflammatory response by inhibiting the PI3K/Akt/eNOS pathway

Lancemaside A, a major triterpene saponin of Codonopsis lanceolata enhances regulation of nitric oxide synthesis via eNOS activation

Astragaloside IV Improves Vasodilatation Function by Regulating the PI3K/Akt/eNOS Signaling Pathway in Rat Aorta Endothelial Cells

Contact Info

Product

Resources

About