Control of blood vessel tone is central to vascular homeostasis. Here, we show that metabolism of tryptophan to kynurenine by indoleamine 2,3-dioxygenase (IDO) expressed in endothelial cells contributes to arterial vessel relaxation and the control of blood pressure. Infection of mice with malarial parasites (Plasmodium berghei), and experimental induction of endotoxemia, caused endothelial expression of IDO, resulting in decreased plasma tryptophan, increased kynurenine, and hypotension. Pharmacological inhibition of IDO increased blood pressure in systemically inflamed mice, but not in mice deficient for IDO or interferon-γ, which is required for IDO induction. Tryptophan dilated pre-constricted porcine coronary arteries only if active IDO and an intact endothelium were both present. Kynurenine dose-dependently decreased blood pressure in spontaneously hypertensive rats, inhibited contraction of arteries, and relaxed pre-constricted rings endothelium-independently. Arterial relaxation by kynurenine was mediated by activation of the adenylate and soluble guanylate cyclase pathways.

The pilot mAFA Trial is the first prospective randomized trial of Mobile Health technology in patients with atrial fibrillation, demonstrating that the mAF App, integrating clinical decision support, education, and patient-involvement strategies, significantly improved knowledge, drug adherence, quality of life, and anticoagulation satisfaction.

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This study identifies that SOST is expressed in the aorta and downregulated in human AA possibly because of epigenetic silencing. Upregulating SOST inhibits AA and atherosclerosis development, with potential important implications for treating these vascular diseases.

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Pristine halloysite nanotubes (HNTs) were pretreated to produce mesoporous silica nanotubes (MSiNTs), which was further impregnated with polyethenimine (PEI) to prepare an emerging nanocomposite MSiNTs/PEI (MP) for CO2 capture. Thermogravimetric analysis (TGA) was employed to analyze the influences of PEI loading amount and adsorption temperature on CO2 adsorption capacity of the nanocomposite. The Brunauer-Emmett-Teller (BET) surface area (SBET) of MSiNTs was six times higher than that of HNTs, and the corresponding pore volume was more than two times higher than that of HNTs. The well dispersion of PEI within the nanotubes of MSiNTs benefits more CO2 gas adsorption, and the adsorption capacity of the nanocomposite could reach 2.75 mmol/g at 85 °C for 2 h. The CO2 adsorption on the nanocomposite was demonstrated to occur via a two-stage process: initially, a sharp linear weight increase at the beginning, and then a relatively slow adsorption step. The adsorption capacity could reach as high as 70% within 2 min. Also, the nanocomposite exhibited good stability on CO2 adsorption/desorption performance, indicating that the as-prepared emerging nanocomposite show an interesting application potential in the field of CO2 capture.

Singlet molecular oxygen ( 1 O 2 ) has well-established roles in photosynthetic plants, bacteria and fungi 1-3 , but not in mammals. Chemically generated 1 O 2 oxidizes the amino acid tryptophan to precursors of a key metabolite called N-formylkynurenine 4 , while enzymatic oxidation of tryptophan to N-formylkynurenine is catalyzed by a family of dioxygenases, including indoleamine 2,3-dioxygenase 1 5 . Under inflammatory conditions, this hemecontaining enzyme becomes expressed in arterial endothelial cells, where it contributes to the regulation of blood pressure 6 . However, whether indoleamine 2,3-dioxygenase 1 forms 1 O 2 and whether this contributes to blood pressure control is unknown. Here we show that arterial indoleamine 2,3-dioxygenase 1 regulates blood pressure via formation of 1 O 2 . We observed that in the presence of hydrogen peroxide, the enzyme generates 1 O 2 and that this is associated with the stereoselective oxidation of L-tryptophan to a tricyclic hydroperoxide via a previously unrecognized oxidative activation of the dioxygenase activity. The tryptophanderived hydroperoxide acts as a hitherto undiscovered signaling molecule in vivo, which induces arterial relaxation and decreases blood pressure dependent on cysteine residue 42 of protein kinase G1α. Our findings demonstrate a pathophysiological role for 1 O 2 in mammals through formation of an amino acid-derived hydroperoxide that regulates vascular tone and blood pressure under inflammatory conditions. Several small molecules, such as nitric oxide and hydrogen peroxide (H 2 O 2 ) regulate cellular signaling via interaction with proteins containing redox active metals and/or cysteine residues. Of these molecules, nitric oxide, formed from L-arginine by endothelial nitric oxide synthase, is an important regulator of vascular tone 7 . Sustained increases in nitric oxide synthesis by inducible nitric oxide synthase, as observed in pathological settings such as sepsis, are associated with profound hypotension 8 . Paradoxically, inhibitors of the nitric oxide pathway have generally failed to ameliorate severe septic shock 9,10 , suggesting involvement of additional mediators of hypotension.Based on functional similarity with the metabolism of L-arginine by nitric oxide synthase, we 3 reported previously that metabolism of L-tryptophan (Trp) to N-formylkynurenine (NFK) and kynurenine by endothelial indoleamine 2,3-dioxygenase 1 (IDO1) ( Fig. 1a) contributes to the regulation of vascular tone and blood pressure in inflammation 6 . We also showed that commercial kynurenine relaxed pre-constricted arteries, which suggested that kynurenine is an endotheliumderived relaxant factor 6 . Although others have since confirmed these findings 11,12 , we noticed that recently purchased kynurenine no longer caused arterial relaxation, and that HPLC-purified kynurenine and NFK also failed to relax naïve mouse arteries ( Fig. 1b). However, purified Trp relaxed pre-constricted mouse abdominal aortas that expressed IDO1, irrespective of whether IDO1 expression was...

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