title: Roles of LOX-1 in microvascular dysfunction.
abstract: Studies from human and animal models with metabolic disease and hypertension highlight atrophic remodeling, reduced lumen size and thinner vascular walls of microvessels with profound density reduction. This impaired vascular response limits the perfusion of peripheral tissues inducing organ damage. These conditions are strongly associated with oxidative stress and in particular with the up-regulation of lectin-like oxidized low density lipoprotein receptor-1 (LOX-1). Several factors such as cytokines, shear stress, and advanced glycation end-products, especially oxLDL, can up-regulate LOX-1. The activation of this receptor induces the production of adhesion molecules, cytokines and the release of reactive oxygen species via NADPH oxidase. LOX-1 is considered a potent mediator of endothelial dysfunction and it is significantly associated with reduced microvascular endothelium NO-dependent vasodilation in hypercholesterolemia and hypertension. Microvascular endothelial cells increased the expression of IL-6 in association with the increased concentration of LDL and its degree of oxidation. Moreover, increased IL-6 levels are associated with up-regulation of LOX-1 in a dose-dependent manner. Another consequence of microvascular inflammation is the generation of small amounts of ROS, similar to those induced by low concentration of oxLDL (<5 μg/mL) which induces capillary tube formation of endothelial cells, through LOX-1 up-regulation. In light of its central role, LOX-1 represents an attractive therapeutic target for the treatment of human atherosclerotic diseases and microvascular disorders.
authors.affiliation: Fondazione CNR/Regione Toscana G. Monasterio, Pisa, Italy. Electronic address: walterl@ftgm.it.
authors.forename: Valter
authors.initials: V
authors.lastname: Lubrano
authors.affiliation: Institute of Clinical Physiology, CNR, Pisa, Italy.
authors.forename: Silvana
authors.initials: S
authors.lastname: Balzan
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism* / Q000503:physiopathology; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D018836:Inflammation Mediators / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008833:Microcirculation; D055806:Microvessels / Q000378:metabolism* / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress; D051127:Scavenger Receptors, Class E / Q000378:metabolism*; D015398:Signal Transduction; D014664:Vasodilation
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D008077:Lipoproteins, LDL; C495137:OLR1 protein, human; D051127:Scavenger Receptors, Class E; C099252:oxidized low density lipoprotein; D009569:Nitric Oxide
keywords: Endothelial function; Free radicals; LOX-1; Microcirculation; Oxidative stress; oxLDL receptor