Table.

Inflammatory Mediators and their role(s) in arterial ageing

Mediator	Abbreviation	Localization	Species	Role in arterial ageing	Key References
Adhesion molecules
e-selectin	N/A	Circulation	Human	Associated with microvascular EDD impairment	(Lind, et al, 2008)
Intracellular adhesion molecule	ICAM	Endothelial, circulation	Human, rat, mouse	Associated with impaired EDD (primarily microvascular), promotes leukocyte adhesion to endothelium	(Csiszar, et al, 2009, Vita, et al, 2004a, Yepuri, et al, 2012)
Vascular cell adhesion molecule	VCAM	Endothelial, circulation	Human, mouse	Associated with impaired cerebral blood flow, promotes leukocyte adhesion to endothelium	(Tchalla, et al, 2015, Yepuri, et al, 2012)
Cytokines & Chemokines
Interferon-γ	IFN-γ	Whole artery	Human, mouse	Gene polymorphisms associated with CVD, EDD impairment	(Annoni, et al, 2009, Lesniewski, et al, 2011, Stokes, et al, 2007)
Interluekin-1β	IL-1β	Endothelial, whole artery, circulation	Human, non-human primate, rat, mouse	Major role in CVD	(Csiszar, et al, 2003, Csiszar, et al, 2012, Lesniewski, Durrant, Connell, Henson, et al., 2011, Ridker, Paul M., et al, 2017)
Interluekin-6	IL-6	Endothelial, circulation	Human,rat	Associated with CVD & large artery stiffness, role in impaired EDD	(Csiszar, et al, 2003, Donato, et al, 2008, Schnabel, et al, 2008, Vita, et al, 2004b, Wassmann, et al, 2004)
Interleukin-17	IL-17	Smooth muscle	Rat	EDD impairment	(Csiszar, et al, 2003, Nguyen, et al, 2013)
Interleukin-10	IL-10	Circulation, whole artery	Human, mouse	Low levels associated with CVD, large artery stiffness, EDD impairment	(Freitas, et al, 2011, Kinzenbaw, et al, 2013)
Transforming Growth Factor-β	TGF-β	Whole artery	Mouse	Collagen deposition, arterial stiffening	(Fleenor, et al, 2010)
Tumour Necrosis Factor-α	TNF-α	Endothelial, smooth muscle, circulation	Human, rat, mouse	Associated with CVD, impaired EDD, role in large artery stiffening	(Belmin, et al, 1995, Csiszar, et al, 2003, Donato, et al, 2008, Machado-Silva, et al, 2016, Moreau, et al, 2013)
CC motif chemokine ligand 2	CCL2, aka Monocyte Chemoattractant protein 1	Endothelial, Smooth muscle, perivascular adipose	Human, mouse	Leukocyte recruitment to artery, promotes large artery stiffening	(Donato, et al, 2008, Wang, et al, 2007, Wang, et al, 2011)
CC motif chemokine ligand 5	CCL5, aka RANTES	Circulating	Human, mouse	Associated with CVD, may promote arterial stiffening	(Grufman, et al, 2014, Lozhkin, et al, 2017)
CXC motif chemokine ligand 2	CXCL2	Smooth muscle, perivascular adipose	Mouse	Recruitment of monocytes to the artery	(Fleenor, et al, 2014, Song, et al, 2012)
CXC motif chemokine ligand 10	CXCL10	Whole artery, smooth muscle	Mouse	Recruitment of T cells to the artery	(Song, et al, 2012, Trott, et al, 2017)
Granuolocyte Macrophage Colony Stimulating Factor	GM-CSF	Whole artery, perivascular adipose	Mouse	Macrophage recruitment to the artery	(Fleenor, et al, 2014, Trott, et al, 2017)
Immune cells
B cells	N/A	Circulation, Perivascular adipose	Mouse	Infiltration of perivascular adipose	(Trott, et al, 2018)
T cells	N/A	Circulation, Perivascular adipose	Human, mouse	Proinflammatory cells associated with large artery stiffness, infiltration of perivascular adipose	(Lesniewski, et al, 2011, Trott, et al, 2018, Yu, et al, 2017)
Monocytes/ Macrophages	N/A	Circulation, Perivascular adipose	Human, mouse	Associated with EDD impairment, infiltration of perivascular adipose promote atherosclerosis	(Du, et al, 2016, Lesniewski, et al, 2011, Trott, et al, 2018, Walker, et al, 2010)
Neutrophils	N/A	Circulation, other?	Human	Associated with microvascular EDD impairment	(Walker, et al, 2010)
Transcription Factors
Nuclear Factor κ B	NFκB	Endothelial, Smooth muscle	Human, non-human primate, rodent	Induces transcription of pro-inflammatory cytokines and chemokines and ROS producing enzymes. Associated with impaired flow mediated dilation and microvascular EDD impairment	(Donato, et al, 2007, Donato, et al, 2008, Donato, et al, 2013, Rodríguez-Mañas, et al, 2009, Ungvari, et al, 2011)
Nuclear factor (erythroid-derived 2)-like 2	Nrf2	Endothelial, smooth muscle	Non-human primate, mouse	Decrease in antoxidant and antiinflammatory gene expression, EDD impairment	(Csiszar, et al, 2012, Fulop, et al, 2018, Ungvari, et al, 2011)
Other
Matrix Metalloproteinase 2	MMP2	Endothelial	Human	Elastin degradation, arterial stiffening	(Wang, et al, 2007)
Matrix Metalloproteinase 9	MMP9	Endothelial, whole artery	Human, mouse	Elastin degradation, arterial stiffening	(Donato, et al, 2013, Wang, et al, 2007)
Toll Like Receptor 4	TLR	Smooth muscle	Rat	Upregulation of IL-6 production	(Song, et al, 2012)
C reactive protein	CRP	Circulation	Human	Associated with CVD & large artery stiffness, role in impaired EDD (primarily microvascular)	(Fichtlscherer, et al, 2000, Hein, et al, 2009, Lind, et al, 2008, Mattace-Raso, et al, 2004)