Analyzer · Sparsifire

Analyze how specific documents activate the features of the SAE. Select a dataset, a run and a document to begin.

Dataset

SAE Model

Document

Active Features

1503

MIN ACTIVATION

0.0

Details List

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Document Content

Increased plasma S-adenosyl-homocysteine levels induce the proliferation and migration of VSMCs through an oxidative stress-ERK1/2 pathway in apoE(-/-) mice.
Although S-adenosyl-homocysteine (SAH) is considered to be a more sensitive predictor of cardiovascular disease than homocysteine, the underlying mechanisms of its effects remain unknown. We investigated the in vivo and in vitro effects of SAH on vascular smooth muscle cells (VSMCs) proliferation and migration related to the development of atherogenesis in apolipoprotein E-deficient (apoE(-/-)) mice. A total of 72 apoE(-/-) mice were randomly divided into six groups (n= 12 for each group). The control group was fed a conventional diet, the M group was fed a 1% methionine-supplemented diet, the A group was fed a diet that was supplemented with the SAH hydrolase (SAHH) inhibitor adenosine-2, 3-dialdehyde (ADA), the M+A group was fed a diet that was supplemented with methionine plus ADA, and two of the groups were intravenously injected with retrovirus that expressed either SAHH shRNA (SAHH(+/-)) or scrambled shRNA semi-weekly for 8 weeks. Compared with the controls, the mice in the A, M+A, and SAHH(+/-) groups had higher plasma SAH levels, larger atheromatous plaques, elevated VSMC proliferation, and higher aortic reactive oxygen species and malondialdehyde levels. In cultured VSMCs, 5 μM ADA or SAHH shRNA caused SAH accumulation, which resulted in increased cell proliferation, migration, oxidative stress, and extracellular-regulated kinase 1/2 (ERK1/2) activation. These effects were significantly attenuated by preincubation with superoxide dismutase (300 U/mL). Our results suggest that elevated SAH induces VSMC proliferation and migration through an oxidative stress-dependent activation of the ERK1/2 pathway to promote atherogenesis.

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