Do Endothelial Cells Eat Tryptophan to Die?

Abstract

The endothelium is a vital homeostatic organ fundamental for the regulation of vascular tone and structure. As such, endothelial dysfunction is intimately linked to the development and progression of cardiovascular disease. The ability of the vasoactive peptide angiotensin II (Ang II) to induce vascular contractility, endothelial cell (EC) apoptosis, and dysfunction via the induction of reactive oxygen species (ROS) is well appreciated.1–3 Vascular NADPH oxidases (Nox) are predominant contributors to Ang II–induced ROS.4 In particular, Nox2 and p47phox proteins are recognized to be involved in Ang II–induced hypertension and endothelial dysfunction,5–8 which is in agreement with in vitro data showing that the activity of the Nox2-based NADPH oxidase activity from EC, although constitutive,9 is augmented by Ang II10 via a mechanism that absolutely requires p47phox phosphorylation and translocation to the plasma membrane.11 Recently, it has also been established that, along with its role in ROS production, Ang II signaling modulates innate and adaptive immunity that critically contributes to the genesis and maintenance of hypertension and vascular dysfunction.12–14 Article, see p 480 In this issue of Circulation Research , additional pieces of the Ang II signaling pathways are connected as Wang et al15 examine a novel mechanism for Ang II–mediated ROS production and vascular dysfunction in vivo involving the crosstalk between interferon-γ (INF-γ) and the kynurenine pathway (Figure 1). The kynurenine pathway is a major catabolic route of tryptophan, an essential amino acid, infrequently found in proteins. This pathway begins …