Table 2.

Deteriorative adipokines for atherosclerosis

Adipokines	Major function	Rank of evidence	References
Leptin	↑piHDL, Lp(a) and apoB100 ↓T-cell helper type 1 response ↑FoxP3 expression and Treg cell function ↑caveolin-1, ERK1/2, eNOS in ECs ↑AngII, ROS, JNK, caveolin-1 in smooth cells ↑TSP-1	****	[53–59, 61, 204, 205]
Chemerin	↑chemerin ∞ ↑ high-sensitivity CRP, IL6, TNF-α, resistin, leptin, BMI, TG, hypertension, ∞ ↓ HDL-C ↑chemerin ∞ ↑ Gensini score ↓chemerin → ↓atherosclerosis, TNFα,IL1β in Apoe−/− mice	***	[67–70]
Resistin	↑ lipid profile,↑ insulin resistance, ↑TG ↑ macrophages polarization, ↑TNF-α, ↑IL-1β, ↑IL-6, ↑VCAM-1, ↑VSMCs, ↑MCP-1, ↑monocyte-endothelial adhesion	****	[71–78]
FABP4	∞ a cluster of metabolic and inflammatory risk factors ↓levels of the adipocyte fatty acid binding protein 4, insulin sensitivity ∞↓cholesterol ester accumulation and inflammatory responses	***	[90–92, 206–212]
IL-1β	expression of various cytokines, chemokines, adhesion molecules ↑leukocytes↑ platelet adhesion to collagen and thrombin↑ VCAM-1↑MCP-1 recruitment↑∞IL-10 produce↓ SMC proliferation↑ and macrophage proliferation in plaques ↑ vascular smooth muscle cell calcium deposition ↑ smooth muscle markers ↑ intimal proliferation↑ advance atherosclerosis: outward remodeling, SMC- and collagen-fibrous cap↑	*****	[95, 97–106, 213, 214]
IL-18	cholesterol efflux (lipoprotein cholesterol↑ serum cholesterol↑) oxidative stress ↑ endothelial dysfunction	*	[110, 111]
	IL18r no differences in atherogenesis induct MMP-9 to promote plaque rupture involve IFN-γ-dependent mechanism to develop atherosclerosis combine with IL-17 promote the diagnostic value of CT	***	[112–118]
IL-6	↑IL-6 ∞ macrophage infiltration in plaque ↑ anti-inflammatory cytokines level in plaques ↑ recruitment of inflammatory cells to the atherosclerotic plaque↑ ↑IL-6 ∞ SMC↑ ↑IL-6 ∞ lipid content ↑ TG ↑ LDL ↑ lipid accumulation↓	****	[121, 122, 126, 215]
	IL-6−/−∞lesion formation↑MMP-9↓pro-inflammatory cytokines↑ IL-6−/−∞serum cholesterol↑	**	[119, 120]
IFN-γ	↓ plaque destabilization,↑ foam cell,↑macrophage activity, ↑oxidative stress,↓IFN-γ∞↓ macrophage, ↓IFN-γ∞↓T lymphocyte ↑mini-TrpRS, ↑VSMC, ↑monocyte adhesion, ↓ECs glucose metabolism, ↑IFN-γ∞↑ECs dysfunction	***	[127, 128, 130, 131, 133, 135–138]
TNF-α	↑pro-atherosclerotic factors, such as ICAM-1, VCAM-1, MCP-1 the paracrine ring between adipose cells and macrophages ↑the migration and proliferation of medial smooth muscle cells ↑the transcytosis of lipoproteins (e.g., LDL) across endothelial cells and macrophages ↑the intracellular cAMP level and the expression level of SRA co-activation of NF-κB and PPAR-γ ↑ DNA binding of Osf2, AP1, CREB and ↑vascular calcification	****	[141–149]
PAI-1	↑neointima formation ↑fibrin(ogen) accumulation; ↑thrombosis ↑cell proliferation and SMCs senescence ↑macrophage invasion	****	[151–155, 158]
RBP4	↑macrophage cholesterol uptake and foam cell formation ↑RBP4 serum levels in patients with established carotid atherosclerosis∞ the severity of atherosclerosis	**	[161, 162]
LCN2	↓the stimulatory effect of lipopolysaccharide on cytokine gene expression ↑the development of aortic atherosclerotic lesions ↑intraplaque monocyte/macrophage infiltration and pentraxin-3 and collagen-1 expressions ↑ the production of IL6 ↑IL-8 ↑ monocyte chemotactic protein-1 in human macrophages ↑human coronary artery smooth muscle cells ↑ THP1 monocyte adhesion to HUVECs accompanied with upregulation of intercellular adhesion molecule-1 ↑vascular cell adhesion molecule-1 ↑E-selectin associated with nuclear factor-κB (NF-κB) upregulation	***	[163, 166, 167]
	∞↓Plaque size		[216]

Rank of evidence: Weak (*), moderate (**), strong (***), stronger (****), Strongest (*****)