Table 1.

Molecules involved in VC process.

Classification	Molecules	Targets	Effects	Involved tissues/cells	Comments	Ref.
Mineral metabolism	Calcium	Pit-1	VC exacerbation	Kidneys, vessels, bones, and intestinal tract	Induces the expression of Pit-1	[43]
	Phosphate	TLR4	VC exacerbation	Kidneys, vessels, bones, and intestinal tract	Activates the TLR4/NF-κB signaling pathway	[32, 113]
	IGF2	Klotho	VC suppression	Kidneys, vessels, and bones	Reduces inflammation and oxidative stress and affects klotho expression	[234, 235]
Hormones	PTH	PTH1R	VC exacerbation	Kidney, vessels, bone, and parathyroid glands	Activates the ERK1/2 and NF-κB signaling pathways	[42]
	AT2	RAS	VC alleviation	Kidneys, vessels, and bones	Stimulates PPAR-γ through klotho expression upregulation	[117, 236]
	Estrogen	HIF-1	VC alleviation	Vessels and bones	Affects BMP-2-p-Smad1/5/8 signaling	[237]
	Growth hormone-releasing hormone	NF-κB, PKA	VC alleviation	Hypothalamus, pituitary, vessels, and bones	Cross talking between the RANKL-NFκB-Runx2 and GHRHR-cAMP-PKA signaling pathways	[238]
Inflammation	IL-6	p53	VC exacerbation	VSMCs	Activates the IL-6/sIL-6R/STAT3/p53/p21 pathway	[25, 239, 240]
	IL-1β	p53	VC exacerbation	VSMCs	Activates the NF-κB/p53/p21 pathway	[144]
	TNF-α	AP-1	VC exacerbation	VSMCs	Activates the TNF- α-AP-1/c-FOS signaling axis	[26]
MicroRNAs	miR-204	DNMT3a	VC alleviation	VSMCs	Affects the MiR-204/DNMT3a regulatory circuit	[192]
	miR-30B	SOX9	VC alleviation	VSMCs	Activates the MMP and autophagy involved in the mTOR signaling pathway	[191]
	miR-135A	KLF-4, STAT3	VC alleviation	VSMCs	Affects the KLF-4/STAT3 pathway	[241]
Enzymes/Small molecules	Phospholipase D	PKC	VC exacerbation	VSMCs	Affects PKC-independent manner activation	[242]
	CDC42	AKT	VC exacerbation	VSMCs	Activates the AKT signaling pathway	[243]
	OGT	Autophagy complex	VC exacerbation	VSMCs	Inhibits autophagy through YAP upregulation	[114]
	IMD1-53	Sirt1 and klotho	VC alleviation	VSMCs	Upregulates Sirt1 by activating the PI3K/Akt and cAMP/PKA signaling pathways and increases α-klotho via the CRLR/RAMP3 complex	[153, 154]
	LGR4	NF-κB	VC exacerbation	Kidneys, vessels, bones, and parathyroid gland	Activates the PTH/PKA signaling pathway	[23]
	MGP	Vitamin K	VC alleviation	Kidneys, vessels, and bones	Activated by vitamin K dependent γ-carboxylation	[45, 163, 244]
	Lamin A	RUNX2	VC exacerbation	VSMCs	Interacts with RUNX2 and facilitates their nuclear localization	[245]
Amino-acid metabolites	Homoarginine	NO	VC exacerbation	Kidney, vessels, and bones	Impairs NO production and triggers osteo-/chondrogenic signaling	[78]
	IS	Klotho, TRPM7	VC exacerbation	VSMCs	Mediates klotho gene expression or downregulates TRPM7, and induces cross-talking between OATP2B1 and Dll4-Notch axes	[79, 122, 123, 129]
	TMAO	NF-κB	VC exacerbation	VSMCs	Activates NLRP3 inflammation and NF-κB signaling	[77]