Necessary Role of Ceramides in the Human Microvascular Endothelium During Health and Disease.

Background: Elevated plasma ceramides and microvascular dysfunction both independently predict adverse cardiac events. Despite the known detrimental effects of ceramide on the microvasculature, evidence suggests that activation of the shear-sensitive, ceramide-forming enzyme NSmase (neutral sphingomyelinase) elicits formation of vasoprotective nitric oxide (NO). Here, we explore a novel hypothesis that acute ceramide formation through NSmase is necessary for maintaining NO signaling within the human microvascular endothelium.

Necessary Role of Acute Ceramide Formation in The Human Microvascular Endothelium During Health and Disease.

Background: Elevated plasma ceramides independently predict adverse cardiac events and we have previously shown that exposure to exogenous ceramide induces microvascular endothelial dysfunction in arterioles from otherwise healthy adults (0-1 risk factors for heart disease). However, evidence also suggests that activation of the shear-sensitive, ceramide forming enzyme neutral sphingomyelinase (NSmase) enhances vasoprotective nitric oxide (NO) production. Here we explore a novel hypothesis that acute ceramide formation through NSmase is necessary for maintaining NO signaling within the human microvascular endothelium.