Globotriaosylsphingosine accumulation and not alpha-galactosidase-A deficiency causes endothelial dysfunction in Fabry disease.

PloS One
Mehdi NamdarGiovanni G Camici

Abstract

Fabry disease (FD) is caused by a deficiency of the lysosomal enzyme alpha-galactosidase A (GLA) resulting in the accumulation of globotriaosylsphingosine (Gb3) in a variety of tissues. While GLA deficiency was always considered as the fulcrum of the disease, recent attention shifted towards studying the mechanisms through which Gb3 accumulation in vascular cells leads to endothelial dysfunction and eventually multiorgan failure. In addition to the well-described macrovascular disease, FD is also characterized by abnormalities of microvascular function, which have been demonstrated by measurements of myocardial blood flow and coronary flow reserve. To date, the relative importance of Gb3 accumulation versus GLA deficiency in causing endothelial dysfunction is not fully understood; furthermore, its differential effects on cardiac micro- and macrovascular endothelial cells are not known. In order to assess the effects of Gb3 accumulation versus GLA deficiency, human macro- and microvascular cardiac endothelial cells (ECs) were incubated with Gb3 or silenced by siRNA to GLA. Gb3 loading caused deregulation of several key endothelial pathways such as eNOS, iNOS, COX-1 and COX-2, while GLA silencing showed no effects. Cardiac microv...Continue Reading

References

Jan 1, 1994·Journal of Neurology·R P Grewal
Jul 1, 1996·Annals of Neurology·P Mitsias, S R Levine
Jun 20, 1998·Neurology·K E CrutchfieldR Schiffmann
Feb 9, 2000·Virchows Archiv : an International Journal of Pathology·A KandaT Kanzaki
Feb 9, 2000·Annals of Neurology·T DeGrabaR Schiffmann
Mar 29, 2000·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·S MeratP D Reaven
Jul 7, 2001·The New England Journal of Medicine·C M EngUNKNOWN International Collaborative Fabry Disease Study Group
Jul 7, 2001·Stroke; a Journal of Cerebral Circulation·G AltarescuR Schiffmann
Jan 23, 2003·Journal of the American Society of Nephrology : JASN·Daniel T EitzmanJames A Shayman
Jan 19, 2005·British Journal of Pharmacology·Paul M VanhoutteStefano Taddei
May 20, 2005·Journal of Inherited Metabolic Disease·R J KalliokoskiP Nuutila
Nov 25, 2005·Journal of Cardiovascular Pharmacology·Eva H C TangPaul M Vanhoutte
Feb 14, 2006·Arteriosclerosis, Thrombosis, and Vascular Biology·Frédéric BarbeyDaniel Hayoz
Jan 17, 2007·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Raymond Y WangWilliam R Wilcox
Mar 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Giovanni G CamiciFrancesco Cosentino
Aug 4, 2007·Virchows Archiv : an International Journal of Pathology·Hasan AskariRaphael Schiffmann
Feb 22, 2008·Proceedings of the National Academy of Sciences of the United States of America·Johannes M AertsBen J Poorthuis
Jun 21, 2008·Clinical and Experimental Pharmacology & Physiology·James L ParkJames A Shayman
Jul 23, 2008·Perspectives in Vascular Surgery and Endovascular Therapy·Kimon Bekelis, Nicos Labropoulos
Oct 23, 2008·Lancet·Yuri A Zarate, Robert J Hopkin
Nov 28, 2008·Kidney International·Thomas ThomaidisAndreas Schwarting
Feb 10, 2009·American Journal of Physiology. Heart and Circulatory Physiology·James L ParkJames A Shayman
Jul 25, 2009·Journal of the American Society of Nephrology : JASN·Liming ShuJames A Shayman
Oct 2, 2009·Basic Research in Cardiology·Cathérine GebhardFelix C Tanner
Nov 11, 2009·Molecular Genetics and Metabolism·S M RombachC E M Hollak

❮ Previous
Next ❯

Citations

Dec 4, 2014·International Journal of Cardiology·Letizia SpinelliBruno Trimarco
Jan 20, 2015·Immunity & Ageing : I & a·Monica Gioia MarazziMassimiliano M Corsi Romanelli
Apr 6, 2016·Frontiers in Cardiovascular Medicine·Mehdi Namdar
Nov 13, 2013·Molecular Genetics and Metabolism·Anatália LabilloyOra A Weisz
Mar 5, 2013·Molecular Genetics and Metabolism·Pablo N De FrancescoPaula A Rozenfeld
Jul 2, 2016·Therapeutic Advances in Gastroenterology·Claire Zar-KesslerBraden Kuo
Dec 11, 2014·Stroke; a Journal of Cerebral Circulation·Edwin KolodnyAlessandro Burlina
Jan 5, 2019·Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society·Martina MasottiMarco Caprini
Jul 5, 2019·Circulation. Cardiovascular Imaging·Kristopher D KnottJames C Moon
Jun 26, 2018·Oncotarget·Giuseppe CammarataGiovanni Duro
Oct 1, 2012·Clinical Kidney Journal·Roser Torra, Alberto Ortíz
Apr 3, 2016·Journal of Neuroscience Research·Mirella Belleri, Marco Presta
Apr 13, 2017·Cell and Tissue Research·Øystein EikremHans-Peter Marti
Sep 16, 2020·Cardiovascular Research·Luca LiberaleGiovanni G Camici
Mar 27, 2021·Clinical and Experimental Nephrology·Sandro Feriozzi, Paula Rozenfeld
Aug 20, 2021·EMBO Molecular Medicine·Chiara SoldatiDiego L Medina

❮ Previous
Next ❯

Methods Mentioned

BETA
FCS
transfection
ELISA

Related Concepts

Related Feeds

Basal Ganglia

Basal Ganglia are a group of subcortical nuclei in the brain associated with control of voluntary motor movements, procedural and habit learning, emotion, and cognition. Here is the latest research.

Cell Adhesion Molecules in AS

Cell adhesion molecules expressed on the vascular endothelium and circulating leukocytes in response to inflammatory stimuli are implicated in atherosclerosis. Here is the latest research.

Birth Defects

Birth defects encompass structural and functional alterations that occur during embryonic or fetal development and are present since birth. The cause may be genetic, environmental or unknown and can result in physical and/or mental impairment. Here is the latest research on birth defects.

Basal Ganglia Cerebrovascular Disease

Basal ganglia cerebrovascular disease is a condition where the blood vessels in the basal ganglia are damaged or malfunction. Discover the latest research on basal ganglia cerebrovascular disease here.