Hyperhomocysteinemia enhances vascular inflammation and accelerates atherosclerosis in a murine model

Although hyperhomocysteinemia (HHcy) is a well-known risk factor for the de velopment of cardiovascular disease, the underlying molecular mechanisms ar e not fully elucidated. Here we show that induction of HHcy in apoE-null mi ce 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 (H C-mediated) effects were significantly suppressed, in parallel with decreas ed levels of plasma HC, upon dietary supplementation with folate and vitami ns B6/B12. These findings implicate HHcy in atherosclerotic plaque progress ion and stability, and they suggest that dietary enrichment in vitamins ess ential for the metabolism of HC may impart protective effects in the vascul ature.