Hyperhomocysteinemia enhances vascular inflammation and accelerates atherosclerosis in a murine model

被引：442

作者：

Hofmann, MA

Lalla, E

Lu, Y

Gleason, MR

Wolf, BM

Tanji, N

Ferran, LJ

Kohl, B

Rao, V

Kisiel, W

Stern, DM

Schmidt, AM

机构：

[1] Columbia Univ, Coll Phys & Surg, New York, NY 10032 USA

[2] Heidelberg Univ, Dept Internal Med, D-6900 Heidelberg, Germany

[3] Univ Texas, Hlth Sci Ctr, Tyler, TX 75710 USA

[4] Univ New Mexico, Sch Med, Albuquerque, NM 87131 USA

来源：

JOURNAL OF CLINICAL INVESTIGATION | 2001年 / 107卷 / 06期

关键词：

D O I：

10.1172/JCI10588

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Although hyperhomocysteinemia (HHcy) is a well-known risk factor for the development of cardiovascular disease, the underlying molecular mechanisms are not fully elucidated. Here we show that induction of HHcy in apoE-null mice by a diet enriched in methionine but depleted in folate and vitamins B6 and B12 increased atherosclerotic lesion area and complexity, and enhanced expression of receptor for advanced glycation end products (RAGE), VCAM-1, tissue factor, and MMP-9 in the vasculature. These homocysteine-mediated (HC-mediated) effects were significantly suppressed, in parallel with decreased levels of plasma HC, upon dietary supplementation with folate and vitamins B6/B12. These findings implicate HHcy in atherosclerotic plaque progression and stability, and they suggest that dietary enrichment in vitamins essential for the metabolism of HC may impart protective effects in the vasculature.

引用

页码：675 / 683

页数：9

共 53 条

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