title: Innate immunity in CKD-associated vascular diseases.
abstract: Chronic kidney disease (CKD) is associated with an increased risk for cardiovascular events. Therefore, the activation of the innate immune system plays an important role. In contrast to the adaptive immunity, unspecific recognition of conserved endogenous and exogenous structures by pattern recognition receptors (PRRs) represents a key feature of the innate immunity. Of these PRRs, Toll-like receptors (TLRs) as well as the inflammasome complex have been documented to be involved in the pathogenesis of cardiovascular diseases (CVDs). They are not only expressed in leukocytes but also in a variety of cell types such as endothelial cells or fibroblasts. While activation of TLRs on the cell surface leads to nuclear factor κB-dependent expression of pro-inflammatory mediators, the inflammasome is a cytosolic multimeric protein complex, which cleaves cytokines such as interleukin-1β into their biologically active forms. Several endogenous ligands for these PRRs have been identified as contributing to the development of a CKD-specific pro-inflammatory microenvironment. Notably, activation of TLRs as well as the inflammasome is associated with arterial hypertension, formation of atherosclerotic vascular lesions and vascular calcification. However, detailed molecular mechanisms on how the innate immune system contributes to CKD-associated CVDs are as yet poorly understood. Currently, several agents modulating the activation of the innate immune system are the focus of cardiovascular research. Large clinical studies will provide further information on the therapeutic applicability of these substances to reduce cardiovascular morbidity and mortality in the general population. Further trials including patients with CKD will be necessary to assess their effects on CKD-associated CVD.
authors.affiliation: Department of Internal Medicine, Nephrology and Hypertension, Saarland University Medical Centre, Homburg/Saar, Germany.
authors.forename: Stephen
authors.initials: S
authors.lastname: Zewinger
authors.affiliation: Department of Internal Medicine, Nephrology and Hypertension, Saarland University Medical Centre, Homburg/Saar, Germany.
authors.forename: Timo
authors.initials: T
authors.lastname: Schumann
authors.affiliation: Department of Internal Medicine, Nephrology and Hypertension, Saarland University Medical Centre, Homburg/Saar, Germany.
authors.forename: Danilo
authors.initials: D
authors.lastname: Fliser
authors.affiliation: Department of Internal Medicine, Nephrology and Hypertension, Saarland University Medical Centre, Homburg/Saar, Germany.
authors.forename: Thimoteus
authors.initials: T
authors.lastname: Speer
mesh_terms: D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000276:immunology*; D014652:Vascular Diseases / Q000209:etiology*
keywords: Toll-like receptors; cardiovascular disease; chronic kidney disease; inflammasome; innate immunity