ArticleArteriosclerosis, thrombosis, and vascular biology2026
Urokinase Plasminogen Activator Deficiency Delays the Development of Obesity and Metabolic Sequelae.
Woosuk S Hur, Yesha N Patel, Sara R Abrahams, Zimu Wei, Haley E Hanes, Angelica T Jameson, Oscar A Negrón, Nadja B Pedersen, Mario S Y Giacomazzo, Else-Marie Bladbjerg and 3 more
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In one paragraphArticle in Arteriosclerosis, thrombosis, and vascular biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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5 · Who and what moneyAuthors and funding
13 authors.
Woosuk S HurDepartment of Pathology and Laboratory Medicine, Blood Research Center, and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill (W.S.H., Y.N.P., S.R.A., H.E.H., A.T.J., O.A.N., A.S.W., M.J.F.).ORCID 0000-0001-5074-6423 Yesha N PatelDepartment of Pathology and Laboratory Medicine, Blood Research Center, and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill (W.S.H., Y.N.P., S.R.A., H.E.H., A.T.J., O.A.N., A.S.W., M.J.F.).ORCID 0000-0002-3635-0091 Sara R AbrahamsDepartment of Pathology and Laboratory Medicine, Blood Research Center, and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill (W.S.H., Y.N.P., S.R.A., H.E.H., A.T.J., O.A.N., A.S.W., M.J.F.).ORCID 0009-0003-3079-8607 Zimu WeiDepartment of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing (Z.W., J.P.L.).ORCID 0000-0002-2944-3118 Haley E HanesDepartment of Pathology and Laboratory Medicine, Blood Research Center, and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill (W.S.H., Y.N.P., S.R.A., H.E.H., A.T.J., O.A.N., A.S.W., M.J.F.).ORCID 0009-0002-2557-1793 Angelica T JamesonDepartment of Pathology and Laboratory Medicine, Blood Research Center, and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill (W.S.H., Y.N.P., S.R.A., H.E.H., A.T.J., O.A.N., A.S.W., M.J.F.).ORCID 0009-0008-3310-3512 Oscar A NegrónDepartment of Pathology and Laboratory Medicine, Blood Research Center, and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill (W.S.H., Y.N.P., S.R.A., H.E.H., A.T.J., O.A.N., A.S.W., M.J.F.).ORCID 0000-0002-5234-8397 Nadja B PedersenUnit for Thrombosis Research, Department of Clinical Biochemistry, University Hospital of Southern Denmark, Esbjerg (N.B.P., E.-M.B.).ORCID 0000-0003-3047-9924 Mario S Y GiacomazzoDepartment of Statistics and Operations Research, University of North Carolina at Chapel Hill (M.S.Y.G.).
Else-Marie BladbjergUnit for Thrombosis Research, Department of Clinical Biochemistry, University Hospital of Southern Denmark, Esbjerg (N.B.P., E.-M.B.).ORCID 0000-0003-0912-2437 Alisa S WolbergDepartment of Pathology and Laboratory Medicine, Blood Research Center, and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill (W.S.H., Y.N.P., S.R.A., H.E.H., A.T.J., O.A.N., A.S.W., M.J.F.).ORCID 0000-0002-2845-2303 James P LuyendykDepartment of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing (Z.W., J.P.L.).
Matthew J FlickDepartment of Pathology and Laboratory Medicine, Blood Research Center, and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill (W.S.H., Y.N.P., S.R.A., H.E.H., A.T.J., O.A.N., A.S.W., M.J.F.).ORCID 0000-0002-5034-3162 Funding
Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI HONG JIN KIM · 1985 to 2026
$201.5MFibrinogen and Factor XIII in Venous ThrombosisR01HL126974 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Alisa S. Wolberg · 2016 to 2026
$4.4MMechanisms linking the plasminogen/fibrinogen axis to the pathogenesis of COVID-19R01HL160046 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI FLICK, MATTHEW J., GRALINSKI, LISA · 2021 to 2024
$2.2MThrombin-dependent mechanisms of pancreatic ductal adenocarcinoma diseaseR01CA211098 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI FLICK, MATTHEW J. · 2017 to 2022
$2.2MNovel mechanisms to limit thrombosis by decreasing fibrinogen or suppressing fibrin matrix formationR01HL168009 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Matthew J. Flick, Christian Kastrup · 2024 to 2026
$2.2MNovel proteolytic mechanisms driving pathologic hepatic congestion in drug-induced hepatotoxicityR01DK135649 · NIDDK · MICHIGAN STATE UNIVERSITY · PI Bryan L Copple, James P Luyendyk · 2023 to 2026
$1.9MFibrin(ogen) control of metabolic inflammation and obesityR01DK112778 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI FLICK, MATTHEW J. · 2019 to 2022
$1.5MNCI NIH HHS P30 CA016086NCI NIH HHS R01 CA211098NHLBI NIH HHS R01 HL126974NHLBI NIH HHS R01 HL160046NHLBI NIH HHS R01 HL168009NIDDK NIH HHS R01 DK112778NIDDK NIH HHS R01 DK135649
6 · The paper itselfAbstract
backgroundObesity predisposes individuals to multiple pathologies, including metabolic dysfunction-associated steatotic liver disease and diabetes. Although it is known that accumulation of proinflammatory macrophages within adipose tissues drives adiposity and provokes obesity-linked sequelae, the molecular mechanisms that provoke macrophage dysfunction in obesity remain elusive. Macrophages express high levels of uPA (urokinase plasminogen activator), and uPA has been implicated in leukocyte migration.
methodsHuman adipose tissues from patients receiving bariatric surgery were collected and analyzed for uPA protein levels. To determine the impact of uPA in adipose tissue and subsequent high-fat diet (HFD)-induced weight gain and metabolic diseases, a novel mouse model with a conditional knockout of uPA (
resultsProtein levels of visceral adipose tissue uPA positively correlated with body mass index in patients with obesity, and uPA levels decreased in adipose tissue 2 years after bariatric surgery. The expression and activity of uPA also increased in the adipose tissue of HFD-fed control mice.
conclusionsOur findings suggest that global uPA deletion, but not selective deletion of uPA in LysM+ myeloid cells, attenuates the development of early-stage HFD-driven obesity and pathologies consistent with metabolic syndrome.
Indexed as
adipose tissuemacrophagesmiceobesityurokinase-type plasminogen activator
Identifiers
PMID41568458
PMCPMC12836328
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