Role for Tetrahydrobiopterin in the Fetoplacental Endothelial Dysfunction in Maternal Supraphysiological Hypercholesterolemia

Table 2

Effect of hypercholesterolemia on tetrahydrobiopterin availability and endothelial function.

Study model	Tissue or cell type	Experimental condition	BH4 level	Parameter	Effect	Reference
Hypercholesterolemia	Human brachial artery	Basal	Reduced	Endothelium dependent vasodilation	Reduced	[13]
		BH4 infusion	Increased	Endothelium dependent vasodilation	Increased
Hypercholesterolemia	Human coronary artery	Basal	Reduced	Coronary artery diameter and flow	Reduced	[51]
		BH4 infusion	Increased	Coronary artery diameter and flow	Increased
Hypercholesterolemia	Human brachial artery	Basal	Reduced	Endothelium dependent vasodilation	Reduced	[52]
		BH4 supplementation	Increased	Endothelium dependent vasodilation	Increased
Hypercholesterolemia	Human coronary microcirculation	Basal	nr	Myocardial blood flow	Reduced	[53]
		BH4 infusion	nr	Myocardial blood flow	Increased
Hypercholesterolemia	Human skin	Basal	nr	Endothelium dependent vasodilation	Reduced	[54]
		R-BH4 infusion	nr	Endothelium dependent vasodilation	Increased
		S-BH4 infusion	nr	Endothelium dependent vasodilation	Reduced
Hypercholesterolemia	Human skin	Basal	nr	Endothelium dependent vasodilation	Reduced	[55]
		BH4 infusion	nr	Endothelium dependent vasodilation	Increased
Cell culture	Human mesenteric microvascular endothelial cells	Incubation with oxLDL	Reduced	NO generation	Reduced	[56]
			Reduced	Superoxide generation	Increased
		Incubation with oxLDL + sepiapterin	Increased	NO generation	Increased
			Increased	Superoxide generation	Reduced
Cell culture	Human aortic endothelial cells	Incubation with LDL	Reduced	NO generation	Reduced	[52]
		Incubation with LDL + BH4	nr	NO generation	Increased

Basal corresponds to no treatment. BH₄: tetrahydrobiopterin; R-BH₄: R-tetrahydrobiopterin (NO synthase cofactor and antioxidant); S-BH₄: stereoisomer of BH₄ (antioxidant); oxLDL: oxidized low-density lipoprotein; LDL: low-density lipoprotein; NO: nitric oxide; nr: not reported.