Globotriaosylceramide Induces Endothelial Dysfunction in Fabry Disease

Abstract

The endothelium critically regulates the contractile status of the vascular smooth muscle cells.1 Dysfunction of endothelial cells (ECs) induces the increased expression of adhesion molecules for inflammatory cells.2 Inflammatory cell migration and vascular inflammation generate an oxidizing environment. The accumulating inflammatory cells produce abundant reactive oxygen species (ROS) and secrete inflammatory cytokines/chemokines and growth factors that contribute to EC dysfunction and vascular smooth muscle cell proliferation.3 Therefore, oxidants were once principally considered agents of vascular injury and disease, and numerous studies have corroborated this role for ROS. However, this has become an outdated theory considering recent evidence suggesting that hydrogen peroxide (H2O2) also serves as an important signaling molecule in the vascular system when found at low concentrations.4 At low concentrations, H2O2 can act as a second messenger, transducing the oxidative signal into a biological response through post-translational protein modification. These structural changes ultimately lead to altered cellular function. See accompanying article on page 81 Oxygen derivatives, including superoxide (O2−), H2O2, and hydroxyl radical (OH), are called ROS. Strictly controlled ROS formation mediates the physiological functions of the vasculature. Therefore, ROS contribute to vascular protection as well as vascular diseases. Vascular ECs themselves produce small amounts of O2− and H2O …