Inhibitory effects of cariporide on LPC-induced expression of ICAM-1 and adhesion of monocytes to smooth muscle cells in vitro

Li, Zhi; Song, Tao; Liu, Guizhen; Liu, Liying

doi:10.1111/j.1745-7254.2006.00412.x

Cited by 10 publications

(4 citation statements)

References 23 publications

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“…Lysophosphatidylcholine (LPC), as a prominent phospholipid component of OxLDL, is responsible for various biological activities of OxLDL, such as regulation of adhesion molecules, NO, cytokines, and growth factors [ 25 , 31 , 33 ]. Recently, several lines of evidence showed that eNOS expression was up-regulated by LPC [ 32 , 43 , 44 ].…”

Section: Discussionmentioning

confidence: 99%

Lysophosphatidylcholine up‐regulates human endothelial nitric oxide synthase gene transactivity by c‐Jun N‐terminal kinase signalling pathway

Xing

Liu

et al. 2009

J Cellular Molecular Medi

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Human endothelial nitric oxide synthase (eNOS) plays a pivotal role in maintaining blood pressure homeostasis and vascular integrity. It has recently been reported that mitogen-activated protein kinases (MAPKs) are intimately implicated in expression of eNOS. However detailed mechanism mediated by them remains to be clarified. In this study, eNOS gene transactivity in human umbilical vein endothelial cells was up-regulated by stimulation of lysophosphatidylcholine (LPC). The stimulation of LPC highly activated both extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK), with differences in the dynamic processes of activation between them. Unexpectedly, p38 MAPK could not be activated by the stimulation of LPC. The activation of JNK signalling pathway by overexpression of JNK or its upstream kinase active mutant up-regulated the transactivity of eNOS significantly, but the activation of p38 signalling pathway down-regulated it largely. The inhibition of either ERK1/2 or JNK signalling pathway by kinase-selective inhibitors could markedly block the induction of the transactivity by LPC. It was observed by electrophoretic mobility shift assay that LPC stimulated both SP1 and AP1 DNA binding activity to go up. Additionally using decoy oligonucleotides proved that SP1 was necessary for maintaining the basal or stimulated transactivity, whereas AP1 contributed mainly to the increase of the stimulated transactivity. These findings indicate that the up-regulation of the eNOS gene transactivity by LPC involves the enhancement of SP1 transcription factor by the activation of JNK and ERK1/2 signalling pathways and AP1 transcription factor by the activation of JNK signalling pathway.

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Section: Discussionmentioning

confidence: 99%

Lysophosphatidylcholine up‐regulates human endothelial nitric oxide synthase gene transactivity by c‐Jun N‐terminal kinase signalling pathway

Xing

Liu

et al. 2009

J Cellular Molecular Medi

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“…Furthermore, cariporide may exert anti-atherogenic effects [15, 28] by inhibiting monocyte adhesion and expression of intercellular adhesion molecule (ICAM) [29]. The potential effect of cariporide on monocytes could be mediated through NHE-1 inhibition [13, 14, 17] or another action.…”

Section: Discussionmentioning

confidence: 99%

Involvement of Signaling Molecules on Na+/H+ Exchanger-1 Activity in Human Monocytes

Sarigianni¹,

Mikhailidis²,

Kaloyianni³

et al. 2010

TOCMJ

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Background: Sodium/hydrogen exchanger-1 (NHE-1) contributes to maintaining intracellular pH (pHi). We assessed the effect of glucose, insulin, leptin and adrenaline on NHE-1 activity in human monocytes in vitro. These cells play a role in atherogenesis and disturbances in the hormones evaluated are associated with obesity and diabetes. Methods and Results: Monocytes were isolated from 16 healthy obese and 10 lean healthy subjects. NHE-1 activity was estimated by measuring pHi with a fluorescent dye. pHi was assessed pre- and post-incubation with glucose, insulin, leptin and adrenaline. Experiments were repeated after adding a NHE-1 inhibitor (cariporide) or an inhibitor of protein kinase C (PKC), nitric oxide synthase (NOS), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, phosphoinositide 3-kinases (PI3K) or actin polymerization. Within the whole study population, glucose enhanced NHE-1 activity by a processes involving PKC, NOS, PI3K and actin polymerization (p = 0.0006 to 0.01). Insulin-mediated activation of NHE-1 (p = <0.0001 to 0.02) required the classical isoforms of PKC, NOS, NADPH oxidase and PI3K. Leptin increased NHE-1 activity (p = 0.0004 to 0.04) through the involvement of PKC and actin polymerization. Adrenaline activated NHE-1 (p = <0.0001 to 0.01) by a process involving the classical isoforms of PKC, NOS and actin polymerization. There were also some differences in responses when lean and obese subjects were compared. Incubation with cariporide attenuated the observed increase in NHE-1 activity. Conclusions: Selective inhibition of NHE-1 in monocytes could become a target for drug action in atherosclerotic vascular disease.

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“…Thus far, more than 100 terrain derivatives have been proposed (Wilson, 2018), consequently forming a complete system of terrain derivative in DTA research. The extraction algorithms of these terrain derivatives and their stability, efficiency, and application classification have always been the research focus of geomorphometry scholars (Li, 2006;Yang et al, 2009;Gomez et al, 2015).…”

Section: Extraction Of Terrain Derivativesmentioning

confidence: 99%

Geomorphology-oriented digital terrain analysis: Progress and perspectives

et al. 2021

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Digital terrain analysis (DTA) is one of the most important contents in the research of geographical information science (GIS). However, on the basis of the digital elevation model (DEM), many problems exist in the current research of DTA in geomorphological studies. For instance, the current DTA research appears to be focused more on morphology, phenomenon, and modern surface rather than mechanism, process, and underlying terrain. The current DTA research needs to be urgently transformed from the study of landform morphology to one focusing on landform process and mechanism. On this basis, this study summarizes the current research status of geomorphology-oriented DTA and systematically reviews and analyzes the research about the knowledge of geomorphological ontology, terrain modeling, terrain derivative calculation, and terrain analytical methods. With the help of DEM data, DTA research has the advantage of carrying out geomorphological studies from the perspective of surface morphology. However, the study of DTA has inherent defects in terms of data expression and analytic patterns. Thus, breakthroughs in basic theories and key technologies are necessary. Moreover, scholars need to realize that DTA research must be transformed from phenomenon to mechanism, from morphology to process, and from terrain to landform. At present, the research development of earth science has reached the critical stage in which the DTA research should focus more on geomorphological ontology. Consequently, this study proposes several prospects of geomorphology-oriented DTA from the aspects of value-added DEM data model, terrain derivatives and their spatial relations, and macro-terrain analysis. The study of DTA based on DEM is at a critical period along with the issue on whether the current GIS technology can truly support the development of geography. The research idea of geomorphology-oriented DTA is expected to be an important exploration and practice in the field of GIS.

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Inhibitory effects of cariporide on LPC-induced expression of ICAM-1 and adhesion of monocytes to smooth muscle cells in vitro

Cited by 10 publications

References 23 publications

Lysophosphatidylcholine up‐regulates human endothelial nitric oxide synthase gene transactivity by c‐Jun N‐terminal kinase signalling pathway

Lysophosphatidylcholine up‐regulates human endothelial nitric oxide synthase gene transactivity by c‐Jun N‐terminal kinase signalling pathway

Involvement of Signaling Molecules on Na+/H+ Exchanger-1 Activity in Human Monocytes

Geomorphology-oriented digital terrain analysis: Progress and perspectives

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