Table 1.

List of selected manuscripts in alphabetical order.

Reference	Title	Sample/Model	AhR Agonist	AhR Antagonist	Main Results
(Agbor et al., 2011) [34]	Endothelial cell-specific aryl hydrocarbon receptor knockout mice exhibit hypotension mediated, in part, by an attenuated angiotensin II responsiveness	Abdominal aorta from WT and ECAhR KO mouse	---	---	Decrease in ATR1 protein expression in abdominal aorta from ECAhR KO. Hypotension in ECAhR KO unrelated to sympathetic or NO contribution. Reduced downstream signalling of Ang II in ECAhR KO.
(Dou et al., 2015) [35]	The cardiovascular effect of the uremic solute indole-3 acetic acid	HUVECs	IAA 5–50 μM	CH-223191 10 μM	Incubation with IAA increases COX-2 mRNA expression by AhR/p38MAPK/NFKB. IAA causes oxidative stress partially mediated by AhR activation. IAA is a predictor of cardiovascular mortality in patients with CKD.
(Fehsel et al., 2022) [36]	Activation of the aryl hydrocarbon receptor by clozapine induces preadipocyte differentiation and contributes to endothelial dysfunction	Aorta from AhR KO mouse	Clozapine 1 μM	CH-223191 10 μM	Decreased Emax in endothelial-dependent vasodilation in the presence of clozapine in WT but not in KO mouse. AhR activity opposes to endothelium- dependent vasodilation.
(da Silva et al., 2022) [37]	Aryl hydrocarbon receptor (AhR) activation contributes to high-fat diet-induced vascular dysfunction	Thoracic aorta from AhR KO mouse fed an HFD HUVECs	---	CH-223191 1 μM	Increase in AhR protein expression in thoracic aorta from WT mice fed an HFD. HFD decreases endothelial-dependent vasodilation in thoracic aorta from WT mice but not from AhR KO mice. Increase in NO production in thoracic aorta from AhR KO mice. In HUVECs, AhR antagonist reverts the decreased levels of NO induced by LPC. AhR KO protects against endothelial dysfunction induced by HFD.
(Gondouin et al., 2013) [38]	Indolic uremic solutes increase tissue factor production in endothelial cells by the aryl hydrocarbon receptor pathway	HUVECs	IS 1 mM IAA 50 μM	---	Increase in TF mRNA levels and eight genes regulated by AhR. IS and IAA increase TF via AhR proning to atherogenesis in CKD patients.
(Ito et al., 2016) [39]	Crucial Role of the Aryl Hydrocarbon Receptor (AhR) in Indoxyl Sulfate-Induced Vascular Inflammation	HUVECs ECAhR KO mouse	IS 0.2–2 mM	---	IS increases leukocyte–endothelial interactions through AP-1 transcriptional activity, and si AhR reverses it in HUVECs. Decrease in inflammation and leukocyte recruitment in ECAhR KO.
(Kim et al., 2017) [40]	Indoxyl sulfate (IS)-mediated immune dysfunction provokes endothelial damage in patients with end-stage renal disease (ESRD)	HUVECs	IS 1 mM	---	TNF-α produced by IS-conditioned monocytes from patients with CKD lead HUVECs to secrete CX3CL1 to further recruit immune cells, promote apoptosis and endothelial cell dysfunction.
(Koizumi et al., 2014) [41]	Aryl hydrocarbon receptor mediates indoxyl sulfate-induced cellular senescence in human umbilical vein endothelial cells	HUVECs	IS 500 μM	α-NF 10 μM CH-223191 10 μM	IS activates NADPH oxidase. IS decreases iNampt and Sirtuin 1 activity, which is reversed by AhR inhibition. AhR blockade may be useful for the treatment of cardiovascular complications in patients with CKD.
(Lano et al., 2020) [42]	Aryl Hydrocarbon Receptor Activation and Tissue Factor Induction by Fluid Shear Stress and Indoxyl Sulfate in Endothelial Cells	HUVECs	IS 200 μM Shear Stress	Genistein	IS and shear stress increase COX-2 and TF mRNA expression. IS induces TF activation with procoagulant effect. SS induces TF activation without procoagulant effect. IS and SS activate AhR by different mechanisms.
(Li et al., 2017) [43]	ITE Suppresses Angiogenic Responses in Human Artery and Vein Endothelial Cells: Differential Roles of AhR	HUVECs HUAECs	ITE 1 μM	---	ITE decreases the proliferation and viability of HUAECs in an AhR-independent manner and HUVECs in an AhR-dependent manner. ITE decreases AhR protein levels in HUAECs and HUVECs. ∙ ITE increases CYP1A1 and CYP1B1 mRNA levels in HUAECs and HUVECs.
(Long et al., 2021) [44]	3′-Oxo-tabernaelegantine A (OTNA) selectively relaxes pulmonary arteries by inhibiting AhR	Pulmonary artery and thoracic aorta from C57BL/6 mouseHUVECs & HPAECs	ITE 20 μM	OTNA CH-223191 10 μM	OTNA inhibits AhR and induces vasodilation in pulmonary artery by activating the PI3K/Akt/eNOS pathway. ITE blocks the vasodilation of OTNA, and CH-223191 produces a synergistic effect with OTNA. AhR inhibition could treat pulmonary arterial hypertension.
(Lund et al., 2008) [45]	Loss of the aryl hydrocarbon receptor induces hypoxemia, endothelin-1, and systemic hypertension at modest altitude	Plasma from AhR KO mouse HUVECs and microvascular ECs from lung	---	---	AhR KO at low altitude induces hypotension. AhR KO at modest altitude induces hypertension. Increase in ET-1 plasma levels in AhR KO does not originate in pulmonary vessels. Decreased in PreproET-1 mRNA levels in AhR-specific siRNA HUVECs and microvascular ECs from lung.
(Masaki et al., 2021) [46]	Aryl hydrocarbon receptor is essential for the pathogenesis of pulmonary arterial hypertension	ECs from SU5416/hypoxia AhR KO rat lung	FICZ 10 mg/kg/wk subcutaneous administration	---	ECs from lung of SU5416/hypoxia rat model have an increase in AhR expression. FICZ, in combination with hypoxia, induces severe PAH. AhR activity is directly proportional to the severity of pathogenesis of PAH.
(Nakagawa et al., 2021) [47]	Indoxyl sulfate induces ROS production via the aryl hydrocarbon receptor-NADPH oxidase pathway and inactivates NO in vascular tissues.	Thoracic aorta from rat	IS 250–1000 μM	CH-223191 10 μM	Increase in O2●− production by IS through activation of NADPH oxidase. Decreased endothelium-dependent vasodilation in the presence of IS that was partially reversed by AhR antagonist.
(Nakagawa et al., 2022) [48]	Acute Kynurenine Exposure of Rat Thoracic Aorta Induces Vascular Dysfunction via Superoxide Anion Production	Thoracic aorta from rat	Kynurenine 10–500 µM	CH-223191 10 μM	Kynurenine increases O2●− production, leading to decreased endothelium-dependent vasodilation.
(Nguyen et al., 2022) [49]	Aryl Hydrocarbon Receptor Inhibition Restores Indoxyl Sulfate-Mediated Endothelial Dysfunction in Rat Aortic Rings.	Aorta from rat	IS 10–300 μM	CH-223191 10 μM	Increase in O2●− production by IS through activation of NADPH oxidase. Decreased endothelium-dependent vasodilation only at IS 300 μM.
(Wang et al., 2016) [50]	Suppression of Lipid Accumulation by Indole-3-Carbinol Is Associated with Increased Expression of the Aryl Hydrocarbon Receptor and CYP1B1 Proteins in Adipocytes and with Decreased Adipocyte-Stimulated Endothelial Tube Formation	Murine preadipocyte cell line 3T3-L1 Human endothelium-derived cell line EA hy926	I3C 50 μM	---	Decrease in pro-angiogenic mediators in adipocytes incubated with I3C. Decrease in endothelial angiogenesis when ECs are incubated with I3C adipocyte conditioned medium.
(Zhang et al., 2022) [51]	Kynurenine promotes neonatal heart regeneration by stimulating cardiomyocyte proliferation and cardiac angiogenesis	CMECs from mouse AhR KO mouse	Kynurenine from cardiomyocytes	---	Kynurenina transport between cardiomyocytes and EC. ∙ Increase in VEGFA gene expression by AhR activation in EC. Decrease in VEGFA in cardiac endothelium from AhR KO.
(Zhang et al., 2010) [52]	An activated renin–angiotensin system maintains normal blood pressure in aryl hydrocarbon receptor heterozygous mice but not in null mice	Thoracic aorta from AhR+/+, AhR+/− and AhR−/− mouse	---	---	Increase in eNOS protein expression in AhR−/−mouse. ∙ Further decrease in mean arterial pressure in AhR−/− than AhR+/− mouse. Further increase in response to ACE inhibitor or ETA antagonist of AhR+/− than AhR−/− mouse.

WT: wild type; ECAhR: Endothelial cell-specific AhR knockout; ATR1: Angiotensin II receptor type 1; NO: Nitric oxide; Ang II: Angiotensin II; HUVECs: Human Umbilical Vein Endothelial Cells; -; Emax: maximal effect; CKD: Chronic kidney disease; HFD: High-fat diet; LPC: Lysophosphatidylcholine; ECs: Endothelial cells; IAA: Indole-3-acetic acid; TF: tissue factor, IS: Indoxyl sulfate, α-NF: α-naphthoflavone; (iNampt): intracellular nicotinamide phosphoribosyltransferase; HUAECs: Human artery endothelial cells; HPAECs: Human pulmonary artery endothelial cells; CMECs: Cardiac microvascular endothelial cells; ITE: 2-(1′H-indole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester; FICZ: formylindolo[3,2-b]carbazole; I3C: Indole-3-carbinol.