Oral atorvastatin therapy restores cutaneous microvascular function by decreasing arginase activity in hypercholesterolaemic humans

摘要

Non-technical summaryA high concentration of cholesterol in the blood, known as hypercholersterolaemia, in the absence of overt atherosclerotic disease induces changes throughout the circulation including an inability to fully respond to vasodilatory stimuli. Here we show that skin blood flow responses are reduced in hypercholersterolaemic men and women partly due to an upregulation of the arginase pathway. Arginase competes for the common substrate l-arginine for the synthesis of the vasoprotective molecule nitric oxide. After 3 months of oral atrovastatin (cholesterol lowering medication) intervention, arginase activity was decreased and skin blood flow responses resembled those of healthy men and women. This suggests that upregulated arginase contributes to decreased vasoreactivity in hyperocholesterolaemic humans and that atrovastatin therapy restores functional vasodilatory properties by decreasing arginase activity.