Genistein inhibits the development of atherosclerosis via inhibiting NF-κB and VCAM-1 expression in LDLR knockout mice

2008 ◽  
Vol 86 (11) ◽  
pp. 777-784 ◽  
Author(s):  
Juejin Wang ◽  
Rongjian Zhang ◽  
Youhua Xu ◽  
Hong Zhou ◽  
Bin Wang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Knockout Mice ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Atherosclerotic Plaques ◽  
Sod Activity ◽  
Density Lipoprotein Receptor ◽  
Total Antioxidant ◽  
Antioxidative Ability

Diet can be an important factor that influences risks for cardiovascular disease. Genistein (4′,5,7-trihydroxyisoflavone), rich in soy, is one candidate that may benefit the cardiovascular system. Here, we explored the effect of genistein in atherosclerosis (AS) development in an in vivo mouse model. Low-density lipoprotein receptor (LDLR) knockout mice were allocated to control, model, and genistein groups. Our results showed that genistein significantly reduced the formation and development of atherosclerotic plaques ((4.68 ± 1.18) ×106 versus (6.65 ± 1.51) ×106 µm2, p < 0.05). In the genistein group, compared with the model group, total antioxidant capacity (TAC) level was 85.5 ± 15.6 versus 203.4 ± 32.6 mmol/L (p < 0.01); malondialdehyde (MDA) level was 3.79 ± 0.28 versus 3.06 ± 0.31 mmol/L (p < 0.01), and superoxide dismutase (SOD) activity was 86.1 ± 6.1 versus 139.1 ± 25.1 U/mL (p < 0.01). Therefore, genistein was able to enhance serum antioxidative ability in our mouse model. Genistein had no influence, however, on serum cholesterol and lipid profiles. Genistein also markedly downregulated the expression of nuclear factor (NF)-κB and vascular cell adhesion molecule (VCAM)-1 in aortas of mice (p < 0.05). These observations suggest that genistein may inhibit AS in LDLR−/− mice via enhancing serum antioxidation and downregulating NF-κB and VCAM-1 expression in the aorta.

The functions of Reelin in membrane trafficking and cytoskeletal dynamics: implications for neuronal migration, polarization and differentiation

2017 ◽  
Vol 474 (18) ◽  
pp. 3137-3165 ◽  
Author(s):  
Jessica Santana ◽  
María-Paz Marzolo
Keyword(s):  
Membrane Trafficking ◽  
Neuronal Migration ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Signaling Cascade ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Density Lipoprotein Receptor ◽  
Reelin Signaling

Reelin is a large extracellular matrix protein with relevant roles in mammalian central nervous system including neurogenesis, neuronal polarization and migration during development; and synaptic plasticity with its implications in learning and memory, in the adult. Dysfunctions in reelin signaling are associated with brain lamination defects such as lissencephaly, but also with neuropsychiatric diseases like autism, schizophrenia and depression as well with neurodegeneration. Reelin signaling involves a core pathway that activates upon reelin binding to its receptors, particularly ApoER2 (apolipoprotein E receptor 2)/LRP8 (low-density lipoprotein receptor-related protein 8) and very low-density lipoprotein receptor, followed by Src/Fyn-mediated phosphorylation of the adaptor protein Dab1 (Disabled-1). Phosphorylated Dab1 (pDab1) is a hub in the signaling cascade, from which several other downstream pathways diverge reflecting the different roles of reelin. Many of these pathways affect the dynamics of the actin and microtubular cytoskeleton, as well as membrane trafficking through the regulation of the activity of small GTPases, including the Rho and Rap families and molecules involved in cell polarity. The complexity of reelin functions is reflected by the fact that, even now, the precise mode of action of this signaling cascade in vivo at the cellular and molecular levels remains unclear. This review addresses and discusses in detail the participation of reelin in the processes underlying neurogenesis, neuronal migration in the cerebral cortex and the hippocampus; and the polarization, differentiation and maturation processes that neurons experiment in order to be functional in the adult brain. In vivo and in vitro evidence is presented in order to facilitate a better understanding of this fascinating system.

Abstract 598: Deletion of Microsomal PGE Synthase-1 Decreases Oxidative Stress and Protects Against Abdominal Aortic Aneurysm Formation in Angiotensin II-Infused Mice

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Miao Wang ◽  
Jane Stubbe ◽  
Eric Lee ◽  
Wenliang Song ◽  
Emanuela Ricciotti ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Angiotensin Ii ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Aortic Aneurysms ◽  
Ang Ii ◽  
Abdominal Aortic ◽  
Density Lipoprotein Receptor ◽  
The Impact

Microsomal (m) prostaglandin (PG) E 2 synthase(S)-1, an enzyme that catalyzes the isomerization of the cyclooxygenase (COX) product, PGH 2 , into PGE 2 , is a major source of PGE 2 in vivo . mPGES-1 deletion in mice was found to modulate experimentally evoked pain and inflammation and atherogenesis is retarded in mPGES-1 knockout (KO) mice. The impact of mPGES-1 deletion on formation of angiotensin II (Ang II)-induced abdominal aortic aneurysms (AAA) was studied in mice lacking the low density lipoprotein receptor (LDLR −/− ). AngII infusion increased aortic macrophage recruitment and nitrotyrosine staining while upregulating both mPGES-1 and COX-2 and urinary excretion of the major metabolite of PGE 2 (PGE-M). Deletion of mPGES-1 decreased both the incidence and severity of AAA and depressed excretion of both PGE-M and 8, 12-iso-iPF 2a -VI, which reflects lipid peroxidation in vivo . While Ang II infusion augmented prostaglandin biosynthesis, deletion of mPGES-1 resulted in rediversion to PGD 2 , reflected by its major urinary metabolite. However, deletion of the PGD 2 receptor, DP1, did not affect AAA in Ang II infused LDLR −/− mice. These observations indicate that deletion of mPGES-1 protects against AAA formation by AngII in hyperlipidemic mice, perhaps by decreasing oxidative stress. Inhibition of mPGES-1 may represent an effective treatment to limit aneurysm occurrence and expansion.

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