. 2020 Dec 10;15(12):e0240669. doi: 10.1371/journal.pone.0240669

Table 2. Basic experimental studies that investigate the anti-inflammatory properties of pre-treatment and post-treatment with RVX.

Species	Tissue/Model	Pre-Treatment (1)	Post-Treatment (2)	Response 1	Response 2	References
Rat	Lung/LPS	RVX	-	TNF-α, MCP-1, IL-1β, PAR-2, NF-κB ↓	-	[50]
		0.2 or 0.4 mg/g,
		10 days
Rat	Femoral Artery/Atherosclerosis Obliterans	-	RVX	-	IL-1, MCP-1, TNF- α, NF-κB,TLR4 ↓	[51]
			10 mg/kg/day
			4 weeks
Rat	Middle Cerebral Artery/Temporary focal cerebral ischaemia	RVX	RVX		IL-1β, IFN-γ, TNF- α, ICAM-1, CD68 ↓	[26]
		3 mg/kg/8 hours	12 mg/kg/ 8 h
		3 mg/kg/8 hours	and 16 h
Mice	Aorta/ApoE -/-	-	RVX	-	TNF- α, IL-6, MCP-1, Egr-1, IFN-γ ↓	[35]
			1 or 5 mg/kg/day
			26 weeks
Mice	Aorta/ApoE -/-	-	RVX	-	TNF- α, COX-2, iNOS, MMP-9, MMP-1 ↓	[14]
			5 mg/kg/day
			20 weeks
Mice	Aorta/ApoE -/-	-	RVX	-	PAR-1,PAR-2, Mac-2, MMP-9 ↓	[63]
			1.2 mg/kg/day
			14 weeks
Mice	EJV/Catheter		RVX	-	MCP-1, MMP-9 ↓	[15]
	Thrombosis		5 mg/kg/day
	Thrombosis		21 days
Mice	Atrial/TAC	-	RVX	-	TNF-α, MCP-1, IL-1β, IL-6, PAR-2 ↓	[21]
			30 μg/g/day
			2 weeks
Mice	Left Ventricle/TAC		RVX		IL-1β, IL-6, IFN-γ, NF-κB, TGF-β, CD-45 ↓	[77]
			1 or 10 mg/kg/day
			3 weeks
Mice	Left Ventricular/Myocardial Ischaemia-RI and TF		RVX		IL-6, PAR-2, collagen	[16]
			0.6 or 1.2 g/kg feed/day		1α2 and 3α1 ↓
			14 days		1α2 and 3α1 ↓
Mice	Heart/Myocardial Infarction	-	138.5mg/kg/day chow		TNF-α, PPAR-1, PAR-2, TGF-β, ↓	[78]
Mice	Heart/Myocardial Infarction	-	7 days		TNF-α, PPAR-1, PAR-2, TGF-β, ↓	[78]
Mice	Aortic root, Coronary Arteries/ICM	-	RVX	-	IL-1β, IL-6, NF-κB	[23]
			10 mg/kg/day		TNF-α, MMP9, MMP12, TIMP1, TGF-β, PAR-1, PAR-2 ↓
			2 weeks		TNF-α, MMP9, MMP12, TIMP1, TGF-β, PAR-1, PAR-2 ↓
Mice	Kidney/Ren-TG Hypertensive	-	RVX	-	TNF-α, MCP-1, Pal-1, PAR-2 ↓	[24]
			6 or 12 mg/kg
			1 or 4 months
Mice	Lung/BERK^ss, vascular Inflammation	-	RVX	-	IL-6, MPO,TAT ↓	[64]
			0.4 mg/g chow
			10 days
Mice	Hind Limb/STZ Diabetes, Ischaemia	RVX	RVX	-	Neovascularisation, CD-31, VEGF ↑	[17]
		1 or 3 mg/kg/day	1 or 3 mg/kg/day
		2 weeks	3 weeks
Mice	Femoral Arteries/Wire-Mediated Vascular Injury	RVX	RVX	-	TNF-α, MCP-1, IL-1β, (TGF)-β1, SDF-1, GM-CSF ↓	[25]
		5 mg/kg/day	5 mg/kg/day
		1 week	1 week
Human	HUVEC/Thrombin	RVX	-	ICAM-1, ELAM-1, IL-8, MCP-1, CXCL1, CXCL2, TF ↓	-	[19]
		0.3–3000 nM
		30 min
Human	HUVEC/Inflammation	RVX	-	TNF-α, IL-6, IL-1β, NF-κB ↓	-	[79]
		1000 nM
		24 hours
Human	HUVEC/FXa Inflammation	-	RVX	-	CCL-2,CCL-5, EDN2, ITGA5, SELE, VCAM-1, TNSF10, MMP-2 ↓	[80]
			50 nM
			12 h
Human	Abdominal Aorta/Aneurysm	-	RVX	-	IL-6, NOS-2, MMP-9 ↓	[20]
Human	Abdominal Aorta/Aneurysm	-	50 nM	-	IL-6, NOS-2, MMP-9 ↓	[20]
Human	Podocytes/Ang-II-induced Inflammation	RVX	-	-	TNF-α, MCP-1, IL-6, PAR-2, NF-κB ↓	[24]
		500 μg/L
		1 hour
Human	Kidney Tubular Cells/AGEs	-	RVX	-	MCP-1, ↓	[62]
			300 nM
			4 hours

Abbreviations: RVX, Rivaroxaban; LPS, Lipopolysaccharide; AGEs, Advanced glycation end products; RI, Reperfusion Injury; Ang-II, Angiotensin II: STZ, Streptozocin; BERK^ss, Berkeley Sicle Cell Mice; Ren-TG, Transgenic Ren-2 Mice;TAC, Transverse Aortic Constriction; ICM,Ischaemic Cardiomyopathy; HUVEC, Human Umbilical Vein Endothelial Cells;TNF-α,Tumour Necrosis Factor Alpha;MCP-1, Monocyte Chemottractant Protein;IL-1β,Interleukin-1 Beta;PAR-2, Protease-Activated Receptor 2;NF-κB, Nuclear Factor Kappa Betta;MMP, Matrix metallopeptidase;GM-CSF,Granulocyte-Macrophage Colony-stimulating Factor; SDF-1,Stromal Cell-Derived Factor 1;VEGF,Vascular Endothelial Growth Factor;NOS-2,Nitric Oxide Synthase-2; Egr-1,Early Growth Response Protein 1;IFN-γ,Interferon Gamma; TF,Thrombin Factor; CCL, C–C Motif Chemokine Ligand, EDN2, Endothelin-2, ITGA5, Integrin Alpha-5/Beta-1; SELE, E-Selectin;TNSF10, Tumor Necrosis Factor (Ligand) Superfamily, Member 10; TLR4, Toll Like Receptor 4.