Acute localized administration of tetrahydrobiopterin and chronic systemic atorvastatin treatment restore cutaneous microvascular function in hypercholesterolaemic humans

摘要

Non-technical summaryA high concentration of cholesterol in the blood, known as hypercholesterolaemia, in the absence of overt atherosclerotic disease induces changes throughout the circulation including an inability to fully respond to vasodilatory stimuli. Here we examined the underlying factors that contribute to reduced skin blood flow responses to local warming in hypercholesterolaemic men and women before and after a common cholesterol-lowering intervention (atorvastatin). We found that skin blood flow responses are reduced in hypercholesterolaemic men and women and that localized administration of the essential enzymatic cofactor, called tetrahydrobiopterin, increases the skin blood flow response to local heating. After 3 months of a cholesterol-lowering intervention (atorvastatin) blood cholesterol was reduced and the skin blood flow responses to local warming were corrected such that there was no longer a difference between the hypercholesterolaemics and the normocholesterolaemic control group. Our data suggest that reduced availability of tetrahydrobiopterin induced by high cholesterol in part contributes to reduced vasodilatory responses in the skin microcirculation which is corrected with a common cholesterol-lowering statin therapy.