Leopold NGAL/Lcn2 and Cardiovascular Fibrosis 21 after exposure because of increased intracellular iron, which is also not surprising given the well-known role of NGAL/Lcn2 in iron transport. In these studies, reactive oxygen species were blocked by the addition of the nicotinamide adenine dinucleotide phosphate oxidase inhibitor apocynin, but the effects of the iron chelator deferiprone on reactive oxygen species generation were not studied. 12 This may be one plausible mechanism to explain an association between iron, oxidant stress, and fibrosis. In fact, in a murine high salt/uninephrectomy model placed on an iron-restricted diet, the decrease in dietary iron attenuated the development of hypertension and renal fibrosis compared with high salt/uninephrectomy-treated controls. Although the aforementioned study did not examine NGAL/Lcn2, it is likely that it played a role in fibrosis. 13 These observations indicate that iron homeostasis be considered a relevant factor in future studies examining aldosterone and cardiovascular injury. Findings from this study implicate adventitial fibroblasts as the effector cell type after NGAL/Lcn2 stimulation; however, there may be a more complex interaction between vascular cells and other cell types with respect to NGAL/Lcn2 and vascular fibrosis. The adventitia is rich in T cells and exposure to deoxycorticosterone acetate/salt increases infiltration of T helper17+ cells into this space in animal models. Aldosterone activates T helper17+ cells to increase interleukin-17 secretion. Interleukin-17, in turn, increases oxidant stress, expression of profibrotic mediators, and fibrosis. When deoxycorticosterone acetate/salt-treated rats were administered an interleukin-17 antibody, these effects were abrogated. 14 It is notable that interleukin-17 upregulates expression of NGAL/Lcn2 directly. 15 These observations likely identify NGAL/Lcn2 as the mechanistic link between aldosterone, immune system activation, and fibrosis but do not tell us if these systems operate simultaneously or in sequence. Taken together, this study identifies NGAL/Lcn2 as an important component of mineralocorticoid-stimulated vascular fibrosis and represents another advance in our understanding of how aldosterone mediates cardiovascular fibrosis. The finding that NGAL/Lcn2, as well as posttranslationally modified forms of this protein, can serve as a circulating biomarker is also relevant and may support a putative strategy for the early initiation of mineralocorticoid receptor blockade to limit fibrosis. Furthermore, more in-depth study of the binding partners of NGAL/Lcn2 may highlight other novel targets in this signaling pathway for future therapeutic intervention.