Atherosclerosis: cell biology and lipoproteins-focus on anti-inflammatory mechanisms as therapeutic options.

DOI:10.1097/MOL.0b013e32835ec608 Atherosclerosis is a chronic inflammatory reaction of the arterial wall characterized by the infiltration of inflammatory cells into the nascent atherosclerotic lesions leading to its growth and eventual destabilization [1,2]. Transforming growth factor beta (TGFb), an anti-inflammatory cytokine, is centrally involved in balancing the immune response in atherosclerosis [3–5]. Recently, Lievens et al. [6 && ] reported that abrogation of TGFb signaling in dendritic cells leads to a two-fold increase in lesion size and acceleration of plaque inflammation. Furthermore, this overexpression of dominant-inactive TGFb receptor in CD11cþ cells increased cytokine production and T-cell content in the plaque. In vitro, dendritic cells deficient in TGFb signaling displayed a profound inflammatory phenotype promoting T-cell activation, proliferation, and differentiation into effector cells, thus providing a mechanistic link to the changes observed in the vasculature. Taken together, this study suggests a potential therapeutic approach in which dendritic cell-specific promotion of TGF signaling may dampen atherosclerosis without the detrimental profibrotic and neoplastic complications caused by systemic TGFR activation. Regulatory T cells (Tregs) are increasingly recognized as potent atheroprotective players [7]. Interestingly, TGFb plays a dual role in Tregs, as it regulates their differentiation and function but also is secreted as one of the most potent effector cytokines. Treg numbers and function were modulated in the atherosclerosis models either by direct adoptive transfer or by indirect measures such as vaccination [8]. Treg function is also mediated by indoleamine 2,3-dioxygenase (IDO) and IDOcatalyzed tryptophan metabolism [9]. The tryptophan metabolite 3-hydroxyanthranilic acid (3-HAA) inhibits inflammation in different experimental autoimmune disease models by repressing proinflammatory T cells and increasing the percentage of Tregs [10]. Zhang et al. [11 && ] now show that 3-HAA reduced atherosclerotic lesion formation in hyperlipidemic mice. Interestingly, 3-HAA