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Sökning: WFRF:(Rye David) > (2022) > Increased soluble u...

LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00005686naa a2200781 4500
001oai:lup.lub.lu.se:d5f3a83a-3afc-47a9-afad-50412b1ec4ec
003SwePub
008230113s2022 | |||||||||||000 ||eng|
0247 a https://lup.lub.lu.se/record/d5f3a83a-3afc-47a9-afad-50412b1ec4ec2 URI
0247 a https://doi.org/10.1172/JCI1587882 DOI
040 a (SwePub)lu
041 a engb eng
042 9 SwePub
072 7a art2 swepub-publicationtype
072 7a ref2 swepub-contenttype
1001 a Hindy, Georgeu Lund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups,Broad Institute,Qatar University4 aut0 (Swepub:lu)med-ghu
2451 0a Increased soluble urokinase plasminogen activator levels modulate monocyte function to promote atherosclerosis
264 1c 2022
520 a People with kidney disease are disproportionately affected by atherosclerosis for unclear reasons. Soluble urokinase plasminogen activator receptor (suPAR) is an immune-derived mediator of kidney disease, levels of which are strongly associated with cardiovascular outcomes. We assessed suPAR’s pathogenic involvement in atherosclerosis using epidemiologic, genetic, and experimental approaches. We found serum suPAR levels to be predictive of coronary artery calcification and cardiovascular events in 5,406 participants without known coronary disease. In a genome-wide association meta-analysis including over 25,000 individuals, we identified a missense variant in the plasminogen activator, urokinase receptor (PLAUR) gene (rs4760), confirmed experimentally to lead to higher suPAR levels. Mendelian randomization analysis in the UK Biobank using rs4760 indicated a causal association between genetically predicted suPAR levels and atherosclerotic phenotypes. In an experimental model of atherosclerosis, proprotein convertase subtilisin/kexin–9 (Pcsk9) transfection in mice overexpressing suPAR (suPARTg) led to substantially increased atherosclerotic plaques with necrotic cores and macrophage infiltration compared with those in WT mice, despite similar cholesterol levels. Prior to induction of atherosclerosis, aortas of suPARTg mice excreted higher levels of CCL2 and had higher monocyte counts compared with WT aortas. Aortic and circulating suPARTg monocytes exhibited a proinflammatory profile and enhanced chemotaxis. These findings characterize suPAR as a pathogenic factor for atherosclerosis acting at least partially through modulation of monocyte function.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Kardiologi0 (SwePub)302062 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Cardiac and Cardiovascular Systems0 (SwePub)302062 hsv//eng
7001 a Tyrrell, Daniel J.u University of Michigan4 aut
7001 a Vasbinder, Alexiu University of Michigan4 aut
7001 a Wei, Changliu Rush University Medical Center Chicago4 aut
7001 a Presswalla, Ferielu University of Michigan4 aut
7001 a Wang, Huiu University of Michigan4 aut
7001 a Blakely, Pennelopeu University of Michigan4 aut
7001 a Ozel, Ayse Bilgeu University of Michigan4 aut
7001 a Graham, Sarahu University of Michigan4 aut
7001 a Holton, Grace H.u University of Michigan4 aut
7001 a Dowsett, Josephu Copenhagen University Hospital4 aut
7001 a Fahed, Akl C.4 aut
7001 a Amadi, Kingsley-michael4 aut
7001 a Erne, Grace K.4 aut
7001 a Tekmulla, Annika4 aut
7001 a Ismail, Anis4 aut
7001 a Launius, Christopher4 aut
7001 a Sotoodehnia, Nona4 aut
7001 a Pankow, James S.4 aut
7001 a Thørner, Lise Wegner4 aut
7001 a Erikstrup, Christian4 aut
7001 a Pedersen, Ole Birger4 aut
7001 a Banasik, Karina4 aut
7001 a Brunak, Søren4 aut
7001 a Ullum, Henrik4 aut
7001 a Eugen-Olsen, Jesper4 aut
7001 a Ostrowski, Sisse Rye4 aut
7001 a Haas, Mary E.4 aut
7001 a Nielsen, Jonas B.4 aut
7001 a Lotta, Luca A.4 aut
7001 a Engström, Gunnaru Lund University,Lunds universitet,Kardiovaskulär forskning - epidemiologi,Forskargrupper vid Lunds universitet,Cardiovascular Research - Epidemiology,Lund University Research Groups4 aut0 (Swepub:lu)smi-gen
7001 a Melander, Olleu Lund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups4 aut0 (Swepub:lu)endo-ome
7001 a Orho-Melander, Marjuu Lund University,Lunds universitet,Diabetes - kardiovaskulär sjukdom,Forskargrupper vid Lunds universitet,Diabetes - Cardiovascular Disease,Lund University Research Groups4 aut0 (Swepub:lu)endo-mor
7001 a Zhao, Lili4 aut
7001 a Murthy, Venkatesh L.4 aut
7001 a Pinsky, David J.4 aut
7001 a Willer, Cristen J.4 aut
7001 a Heckbert, Susan R.4 aut
7001 a Reiser, Jochen4 aut
7001 a Goldstein, Daniel R.4 aut
7001 a Desch, Karl C.4 aut
7001 a Hayek, Salim S.4 aut
7102 a Kardiovaskulär forskning - hypertonib Forskargrupper vid Lunds universitet4 org
7730 t Journal of Clinical Investigationg 132:24, s. 1-14q 132:24<1-14x 0021-9738
8564 u https://www.jci.org/articles/view/158788y FULLTEXT
8564 u http://dx.doi.org/10.1172/JCI158788x freey FULLTEXT
8564 8u https://lup.lub.lu.se/record/d5f3a83a-3afc-47a9-afad-50412b1ec4ec
8564 8u https://doi.org/10.1172/JCI158788

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