Increased levels of proinflammatory interleukin-6 and monocyte chemoattractant protein-1 were preferentially colocalized within adventitial fibroblasts in HHcy plus angiotensin II mice, which suggested the importance of adventitial fibroblasts activation in Hcy-aggravated AAA.
Severe HHcy accelerated atherosclerosis and inflammatory monocyte/macrophage accumulation in lesions and increased plasma tumor necrosis factor-alpha and monocyte chemoattractant protein-1 levels in Tg-hCBS apoE(-/-) Cbs(-/-) mice fed a high-fat diet.
We investigated the effect of hyperhomocysteinemia on MCP-1 expression and the molecular mechanism underlining such an effect in rat kidneys as well as in proximal tubular cells.
Of note, 2-week hyperhomocysteinemia (HHcy) ApoE(-/-) mice showed accelerated lesion formation and parallel lower Trx expression in macrophages than ApoE(-/-) mice, suggesting that HHcy-induced sustained oxidative stress in vivo might account for impaired Trx and hence increased ROS production and MCP-1 secretion from macrophages, and subsequently accelerated atherogenesis.
The positive correlation between MCP-1 and Hcy concentrations is consistent with the hypothesis that active inflammation and hyperhomocysteinemia are etiologically linked.
Four-week HHcy apoE-/- mice showed more plaques and significantly increased immunostaining of Ref-1 and MCP-1 in foam cells, and HHcy mice showed enhanced Ref-1 expression in peritoneal macrophages.