TABLE 1.

Molecules exhibiting an enhanced gene and protein expression in the aortic valve in diabetes/diabetic conditions

Family	Name	Gene and proteins Increased expression	Cell Location	Condition	Model	Ref.
Cytokines	MCP−1	MCP−1 gene	VECs, VICs	HG	3D model of the human aortic valve	60
		Soluble MCP−1 protein	CM
	TNF‐α	TNF‐α gene	VECs, VICs CM
	IL8	IL8 gene
	ILl‐β	ILl‐β gene
	ILl‐β	Soluble ILl‐β protein
Cell adhesion molecules	VCAM−1	VCAM−1 protein	VECs	HG	2D	50
		VCAM−1 gene	VECs, VICs	HG	3D	60
		VCAM−1 protein	Aortic valve	Early DM	HLD mouse	41
	ICAM−1	ICAM−1 protein
	P‐selectin	P‐selectin protein
	E‐selectin	E‐selectin protein	VECs	HG	2D	60
		E‐selectin gene	VECs, VICs	HG	3D	60
	IC α4	IC α4 gene	VECs
	IC αv	IC αv gene
	IC β1	IC β1 gene
	IC β3	IC β3 gene	VECs, VICs
	IC β5	IC β5 gene
TGF‐β family members	TGF–β	Soluble TGF–β protein	CM	HG	3D
		TGF–β protein	Aortic valve	Early DM	HLD mouse	41
	BMP−2	BMP−2 protein
		Soluble BMP−2	CM	HG	3D	59
		BMP−2 gene	VECs, VICs
	BMP−4	BMP−4 protein	Aortic valve	Early DM	HLD mouse
		BMP−4 gene	VECs, VICs	HG	3D	60
Osteogenic molecules	OC	OC protein	Aortic valve	Early DM	HLD mouse	41
		OC gene	VICs	HG	3D	59
	OP	OP protein	Aortic valve	Early DM	HLD mouse	41
		OP protein		6‐mo DM	LAI mouse	40
		OP protein	VICs	βGP	2D	44
		OP gene		HG	3D	59
	ALP	ALP protein	Aortic valve	DM	DM patients	60
		ALP protein		Early DM	HLD mouse
ECM proteins	FN	FN protein	Aortic valve	Early DM	HLD mouse	41
	LAM	LAM gene	VECs	HG	3D	60
	COL III	COL III gene	VICs
MMPs	MMP−2	MMP−2 protein	Aortic valve	Early DM	HLD mouse	41
	MMP−9	MMP−9 protein
	MMP−1	MMP−1gene	VICs	HG	3D	59
	MMP−13	MMP−13 gene
SLPGs	BYG	BYG gene	Aortic valve	DM	DM patients	44
		BYG protein
		BYG protein	VICs	βGP	2D
AGEs	AGEs	AGEs	Aortic valve	DM	DM patients	46
			Plasma
AGEs receptors	RAGE	RAGE	Human Aortic valve	DM	DM patients	46
			Plasma
GPs	vWF	vWF gene	VECs	HG	3D	60
Actin protein family	α‐SMA	α‐SMA protein	Aortic valve	Early DM	HLD mouse	41
S100 family	S100‐A4	S100‐A4 protein	Aortic valve	Early DM	HLD mouse	41
Annexins	ANXII	ANXII protein	Aortic valve	DM	DM patients	5
TX factors	RUNX−2	RUNX−2 protein	Aortic valve	DM	DM patients	5
		RUNX−2 gene	VECs, VICs	HG	3D
		RUNX−2 protein	VICs			59
Signal transducers	pSMAD1/5/8/9	pSMAD1/5/8/9 protein	VICs	HG	3D	59
	pSMAD 2/3	pSMAD 2/3protein	VECs, VICs
	pPKC	pPKC protein				60

Abbreviations: 2D, Two‐dimensional model; 3D, Three‐dimensional model; AGEs, Advanced glycation end products; ALP, Alkaline phosphatase; ANX, Annexin; BMP, Bone morphogenetic protein; BYG, Biglycan; CM, Conditioned media; COL III, Type III collagen; DM, Diabetes mellitus; FN, Fibronectin; HG, High‐glucose media; HLD, Hyperlipemic diabetic; IC, Integrin chain; ICAM‐1, Intercellular adhesion molecule 1; IL‐1β, Interleukin 1 beta; IL‐8, Interleukin 8; LAI, Diabetes mellitus‐prone LDLr−/−/ApoB100/100/IGF‐II; LAM, Laminin gamma chain; MCP‐1, Monocyte chemoattractant protein1; MMP, Matrix metalloproteinase; OC, Osteocalcin; OP, Osteopontin; pPKC, Phosphorylated protein kinase C; pSMAD, Phosphorylated SMAD; RAGE, AGE receptor; Ref, Reference cited; RUNX‐2, Runt‐related transcription factor 2; S100‐A4, S100 calcium‐binding protein A4; SLPGs, Small leucine‐rich proteoglycans; TGF‐β, Transforming growth factor beta; TNF‐α, Tumor necrosis factor alpha; TX, Transcription; VCAM‐1, Vascular cell adhesion molecule 1; VECs, Valvular endothelial cells; VICs, Valvular interstitial cells; vWF, Von Willebrand factor; α‐SMA, α‐ smooth muscle actin; βGP, β‐Glycero‐phosphate stimulation.