Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Epidermal growth factor (EGF) has been shown to be a potent mitogen for vascular smooth muscle cells (VSMC) both in vitro and in vivo, thus contributing to the development of atherosclerosis and hypertension. Stimulation of Rho-family GTPases Rac/Cdc42 exerts pleiotropic cellular effects and have been demonstrated to contribute to EGF-induced proliferation in other cell systems. However, the effect of EGF on Rac/Cdc42 activation is unknown for VSMC. In the present report, we evaluated stimulation of Rac/Cdc42 by EGF in VSMC performing PAK-PBD binding assay. EGF treatment of VSMC induced time and concentration dependent binding of GTP-bound Rac1 to PAK-PBD peaking at 1 min and showing sustained activation up to 15 min. However, stimulation of Cdc42 could not be demonstrated. To further evaluate downstream effectors of Rac1 stimulation of p21-activated kinase (PAK) and c-Jun N-terminal kinase (JNK) by EGF was determined. In VSMC, EGF sequentially stimulated PAK, peaking at 5 min, and JNK, peaking at 15 min. Pretreatment of VSMC by EGF receptor specific tyrosine kinase inhibitor AG1478 and non-specific tyrosine kinase inhibitor genistein inhibited EGF-induced activation of Rac1, PAK and JNK, whereas tyrosine kinase inhibitors specific for Src (PP1) and specific for platelet-derived growth factor (AG1296) had no effect. Specific inhibition or Rac1 by NSC23766 attenuated EGF-induced [(3)H] thymidine incorporation in VSMC. Our data provide evidence for EGF-induced Rac1 activation and implicate PAK and JNK as downstream targets of Rac1 in EGF signal transduction in VSMC.
Atherosclerosis 2008 Jan
PMID:Epidermal growth factor stimulates Rac1 and p21-activated kinase in vascular smooth muscle cells. 1735 25

Disturbed flow can eliminate the alignment of endothelial cells in the direction of laminar flow, and significantly impacts on atherosclerosis in collateral arteries near the bifurcation and high curvature regions. While shear stress induced Rac polarity has been shown to play crucial roles in cell polarity and migration, little is known about the spatiotemporal map of Rac under disturbed flow, and the mechanism of flow-induced cell polarity still needs to be elucidated. In this paper, disturbed flow or laminar flow with 15 dyn/cm2 of average shear stress was applied on bovine aortic endothelial cells (BAECs) for 30 minutes. A genetically-encoded PAK-PBD-GFP reporter was transfected into BAECs to visualize the real-time activation of Rac in living cell under fluorescence microscope. The imaging of the fluorescence intensity was analyzed by Matlab and the normalized data was converted into 3D spatiotemporal map. Then the changes of data upon chemical interference were fitted with logistic curve to explore the rule and mechanism of Rac polarity under laminar or disturbed flow. A polarized Rac activation was observed at the downstream edge along the laminar flow, which was enhanced by benzol alcohol-enhanced membrane fluidity but inhibited by nocodazole-disrupted microtubules or cholesterol-inhibited membrane fluidity, while no obvious polarized Rac activation could be found upon disturbed flow application. It is concluded that disturbed flow inhibits the flow-induced Rac polarized activation, which is related to the interaction of cell membrane and cytoskeleton, especially the microtubules.
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PMID:Visualizing the spatiotemporal map of Rac activation in bovine aortic endothelial cells under laminar and disturbed flows. 2919 Jul 56

Objectives: The objective of this study was to demonstrate the feasibility of using noninvasive photoacoustic imaging technology along with novel semiconducting polymer nanoparticles for in vivo identifying inflammatory components in carotid atherosclerosis and assessing the severity of inflammation using mouse models. Methods and Results: Healthy carotid arteries and atherosclerotic carotid arteries were imaged in vivo by the noninvasive photoacoustic imaging system. Molecular probes PBD-CD36 were used to label the inflammatory cells to show the inflammation information by photoacoustic imaging. In in vivo imaging experiments, we observed the maximum photoacoustic signal enhancement of 4.3, 5.2, 8 and 16.3 times between 24 h post probe injection and that before probe injection in four carotid arteries belonging to three atherosclerotic mice models. In the corresponding carotid arteries stained with CD36, the ratio of 0.043, 0.061, 0.082 and 0.113 was found between CD36 positive (CD36(+)) expression area and intima-media area (P < 0.05). For the CD36(+) expression less than 0.008 in eight arteries, no photoacoustic signal enhancement was found due to the limited system sensitivity. The photoacoustic signal reflects CD36(+) expression in plaques, which shows the feasibility of using photoacoustic imaging for in vivo assessment of carotid atherosclerosis. Conclusion: This research demonstrates a semiconducting polymer nanoparticle along with photoacoustic technology for noninvasive imaging and assessment of inflammation of carotid atherosclerotic plaques in vivo.
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PMID:In vivo assessment of inflammation in carotid atherosclerosis by noninvasive photoacoustic imaging. 3229 23