ArticleCirculation research2026
LATS1/2-CD38 Metabolic Rewiring Links Senescence to Intraplaque Thrombosis.
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Article in Circulation research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Mechanometabolic endothelial senescence as a translational framework for cardiometabolic vascular disease and vascular ageing.Molecular biology reports · 2026Review
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Authors and funding
45 authors.
Sivareddy Kotla *Department of Cardiology (S.K., J.L., K.A.K., V.S.K.S., O.H., G.F.M., L.A.R., M.I., K.C.T.S., J.H.K., K.C.O.-M., K.N.M.-R., A.D., K.F., N.L.P., E.K., Y.J.G., J.-I.A.), The University of Texas MD Anderson Cancer Center, Houston.ORCID 0000-0001-7516-7647
Jonghae Lee *Department of Cardiology (S.K., J.L., K.A.K., V.S.K.S., O.H., G.F.M., L.A.R., M.I., K.C.T.S., J.H.K., K.C.O.-M., K.N.M.-R., A.D., K.F., N.L.P., E.K., Y.J.G., J.-I.A.), The University of Texas MD Anderson Cancer Center, Houston.ORCID 0000-0002-1182-9653
Kyung Ae Ko *Department of Cardiology (S.K., J.L., K.A.K., V.S.K.S., O.H., G.F.M., L.A.R., M.I., K.C.T.S., J.H.K., K.C.O.-M., K.N.M.-R., A.D., K.F., N.L.P., E.K., Y.J.G., J.-I.A.), The University of Texas MD Anderson Cancer Center, Houston.
Weiqing Chen *Department of Cardiovascular Sciences, Houston Methodist Research Institute, Houston, TX (W.C., S.L., G.W., N.-T.L., J.P.C.).ORCID 0000-0003-3539-9210
Venkata Subrahmanya Kumar SamanthapudiDepartment of Cardiology (S.K., J.L., K.A.K., V.S.K.S., O.H., G.F.M., L.A.R., M.I., K.C.T.S., J.H.K., K.C.O.-M., K.N.M.-R., A.D., K.F., N.L.P., E.K., Y.J.G., J.-I.A.), The University of Texas MD Anderson Cancer Center, Houston.ORCID 0009-0004-2445-0396
Oanh HoangDepartment of Cardiology (S.K., J.L., K.A.K., V.S.K.S., O.H., G.F.M., L.A.R., M.I., K.C.T.S., J.H.K., K.C.O.-M., K.N.M.-R., A.D., K.F., N.L.P., E.K., Y.J.G., J.-I.A.), The University of Texas MD Anderson Cancer Center, Houston.ORCID 0000-0001-5304-585X
Gilbert F MejiaDepartment of Cardiology (S.K., J.L., K.A.K., V.S.K.S., O.H., G.F.M., L.A.R., M.I., K.C.T.S., J.H.K., K.C.O.-M., K.N.M.-R., A.D., K.F., N.L.P., E.K., Y.J.G., J.-I.A.), The University of Texas MD Anderson Cancer Center, Houston.ORCID 0009-0004-4048-2013
Shengyu LiDepartment of Cardiovascular Sciences, Houston Methodist Research Institute, Houston, TX (W.C., S.L., G.W., N.-T.L., J.P.C.).ORCID 0009-0000-7809-2046
Hani LeeDepartment of Pulmonary Medicine, Section of Benign Hematology, The University of Texas MD Anderson Cancer Center, Houston (H.L., M.S.C., V.A.-K.).ORCID 0000-0002-3706-6906
Aijun ZhangDepartment of Medicine, Center for Bioenergetics, Houston Methodist Research Institute, TX (A.Z., D.J.H.).ORCID 0000-0003-1491-8528
Min Soon ChoDepartment of Pulmonary Medicine, Section of Benign Hematology, The University of Texas MD Anderson Cancer Center, Houston (H.L., M.S.C., V.A.-K.).ORCID 0000-0002-9992-8356
Keri L SchadlerDepartment of Pediatrics-Research (J.L., K.L.S.), The University of Texas MD Anderson Cancer Center, Houston.ORCID 0000-0002-1675-0514
Luis Antonio RiveraDepartment of Cardiology (S.K., J.L., K.A.K., V.S.K.S., O.H., G.F.M., L.A.R., M.I., K.C.T.S., J.H.K., K.C.O.-M., K.N.M.-R., A.D., K.F., N.L.P., E.K., Y.J.G., J.-I.A.), The University of Texas MD Anderson Cancer Center, Houston.ORCID 0009-0003-9151-3345
Masaki ImanishiDepartment of Cardiology (S.K., J.L., K.A.K., V.S.K.S., O.H., G.F.M., L.A.R., M.I., K.C.T.S., J.H.K., K.C.O.-M., K.N.M.-R., A.D., K.F., N.L.P., E.K., Y.J.G., J.-I.A.), The University of Texas MD Anderson Cancer Center, Houston.
Kay Carlene Tavares SamperioDepartment of Cardiology (S.K., J.L., K.A.K., V.S.K.S., O.H., G.F.M., L.A.R., M.I., K.C.T.S., J.H.K., K.C.O.-M., K.N.M.-R., A.D., K.F., N.L.P., E.K., Y.J.G., J.-I.A.), The University of Texas MD Anderson Cancer Center, Houston.
Jung Hyun KimDepartment of Cardiology (S.K., J.L., K.A.K., V.S.K.S., O.H., G.F.M., L.A.R., M.I., K.C.T.S., J.H.K., K.C.O.-M., K.N.M.-R., A.D., K.F., N.L.P., E.K., Y.J.G., J.-I.A.), The University of Texas MD Anderson Cancer Center, Houston.ORCID 0009-0006-8526-1315
Kelia C Ostos-MendozaDepartment of Cardiology (S.K., J.L., K.A.K., V.S.K.S., O.H., G.F.M., L.A.R., M.I., K.C.T.S., J.H.K., K.C.O.-M., K.N.M.-R., A.D., K.F., N.L.P., E.K., Y.J.G., J.-I.A.), The University of Texas MD Anderson Cancer Center, Houston.ORCID 0009-0009-7368-4224
Karla N Mariscal-ReyesDepartment of Cardiology (S.K., J.L., K.A.K., V.S.K.S., O.H., G.F.M., L.A.R., M.I., K.C.T.S., J.H.K., K.C.O.-M., K.N.M.-R., A.D., K.F., N.L.P., E.K., Y.J.G., J.-I.A.), The University of Texas MD Anderson Cancer Center, Houston.
Anita DeswalDepartment of Cardiology (S.K., J.L., K.A.K., V.S.K.S., O.H., G.F.M., L.A.R., M.I., K.C.T.S., J.H.K., K.C.O.-M., K.N.M.-R., A.D., K.F., N.L.P., E.K., Y.J.G., J.-I.A.), The University of Texas MD Anderson Cancer Center, Houston.ORCID 0000-0002-6147-9591
John P CookeDepartment of Cardiovascular Sciences, Houston Methodist Research Institute, Houston, TX (W.C., S.L., G.W., N.-T.L., J.P.C.).ORCID 0000-0003-0033-9138
Keigi FujiwaraDepartment of Cardiology (S.K., J.L., K.A.K., V.S.K.S., O.H., G.F.M., L.A.R., M.I., K.C.T.S., J.H.K., K.C.O.-M., K.N.M.-R., A.D., K.F., N.L.P., E.K., Y.J.G., J.-I.A.), The University of Texas MD Anderson Cancer Center, Houston.ORCID 0000-0002-9267-9190
Nicolas L PalaskasDepartment of Cardiology (S.K., J.L., K.A.K., V.S.K.S., O.H., G.F.M., L.A.R., M.I., K.C.T.S., J.H.K., K.C.O.-M., K.N.M.-R., A.D., K.F., N.L.P., E.K., Y.J.G., J.-I.A.), The University of Texas MD Anderson Cancer Center, Houston.ORCID 0000-0001-7565-1797
Efstratios KoutroumpakisDepartment of Cardiology (S.K., J.L., K.A.K., V.S.K.S., O.H., G.F.M., L.A.R., M.I., K.C.T.S., J.H.K., K.C.O.-M., K.N.M.-R., A.D., K.F., N.L.P., E.K., Y.J.G., J.-I.A.), The University of Texas MD Anderson Cancer Center, Houston.ORCID 0000-0002-6757-6480
Young Jin GiDepartment of Cardiology (S.K., J.L., K.A.K., V.S.K.S., O.H., G.F.M., L.A.R., M.I., K.C.T.S., J.H.K., K.C.O.-M., K.N.M.-R., A.D., K.F., N.L.P., E.K., Y.J.G., J.-I.A.), The University of Texas MD Anderson Cancer Center, Houston.ORCID 0009-0003-2200-2795
Rajneesh PathaniaDepartment of Veterinary Medicine & Surgery (R.P.), The University of Texas MD Anderson Cancer Center, Houston.
Craig MorrellDepartment of Medicine, Aab Cardiovascular Research Institute (C.M.), University of Rochester, NY.ORCID 0000-0001-9131-4862
Philip L LorenziDepartment of Bioinformatics and Computational Biology (P.L.L., L.T., I.M.), The University of Texas MD Anderson Cancer Center, Houston.ORCID 0000-0003-0385-7774
Lin TanDepartment of Bioinformatics and Computational Biology (P.L.L., L.T., I.M.), The University of Texas MD Anderson Cancer Center, Houston.
Iqbal MahmudDepartment of Bioinformatics and Computational Biology (P.L.L., L.T., I.M.), The University of Texas MD Anderson Cancer Center, Houston.ORCID 0000-0001-7729-8122
Nordin M J HanssenDepartment of (Experimental) Vascular and Internal Medicine, Amsterdam UMC, the Netherlands (N.M.J.H.).ORCID 0000-0001-9541-7244
Vahid Afshar-KharghanDepartment of Pulmonary Medicine, Section of Benign Hematology, The University of Texas MD Anderson Cancer Center, Houston (H.L., M.S.C., V.A.-K.).ORCID 0000-0003-2911-1284
Dale J HamiltonDepartment of Medicine, Center for Bioenergetics, Houston Methodist Research Institute, TX (A.Z., D.J.H.).ORCID 0000-0002-2481-2746
Laurent Yvan-CharvetInstitut National de la Santé et de la Recherche Médicale (Inserm) U1065, Université Côte d'Azur, Centre Méditerranéen de Médecine Moléculaire (C3M), Fédération Hospitalo-Universitaire (FHU) Oncoage, IHU Respiratory Health, Environment and Ageing (RespirERA), Nice, France (L.Y.-C.).ORCID 0000-0002-7748-4942
Eduardo N ChiniDepartment of Anesthesiology and Perioperative Medicine, Mayo Clinic, Jacksonville, FL (E.N.C.).ORCID 0000-0003-1555-4834
Joerg HerrmannDepartment of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (J.H.).ORCID 0000-0001-6675-4559
Hernan G VasquezMichael E. Debakey Department of Surgery, Baylor College of Medicine, Houston, TX (H.G.V., Y.H.S.).
Ying H ShenMichael E. Debakey Department of Surgery, Baylor College of Medicine, Houston, TX (H.G.V., Y.H.S.).ORCID 0000-0003-4119-115X
James F MartinDepartment of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX (J.F.M.).ORCID 0000-0002-7842-9857
Haodong XuDepartment of Anatomic Pathology, Wake Forest University School of Medicine, Winston-Salem, NC (H.X.).
Erin H SeeleyDepartment of Chemistry, the University of Texas at Austin (E.H.S.).ORCID 0000-0002-8000-5754
Jared K BurksDepartment of Bioinformatics and Computational Biology (P.L.L., L.T., I.M.), The University of Texas MD Anderson Cancer Center, Houston.ORCID 0000-0002-6173-9074
Paul S BrookesDepartment of Anesthesiology and Perioperative Medicine (P.S.B.), University of Rochester, NY.ORCID 0000-0002-8639-8413
Guangyu WangDepartment of Cardiovascular Sciences, Houston Methodist Research Institute, Houston, TX (W.C., S.L., G.W., N.-T.L., J.P.C.).ORCID 0000-0003-4803-7200
Nhat-Tu LeDepartment of Cardiovascular Sciences, Houston Methodist Research Institute, Houston, TX (W.C., S.L., G.W., N.-T.L., J.P.C.).ORCID 0000-0001-7746-7328
Jun-Ichi AbeDepartment of Cardiology (S.K., J.L., K.A.K., V.S.K.S., O.H., G.F.M., L.A.R., M.I., K.C.T.S., J.H.K., K.C.O.-M., K.N.M.-R., A.D., K.F., N.L.P., E.K., Y.J.G., J.-I.A.), The University of Texas MD Anderson Cancer Center, Houston.ORCID 0000-0001-7439-7774
Funding
Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DIANE BODURKA · 1985 to 2026
$290.8MSIRT1, Nitro-Lipids and CardioprotectionR01HL071158 · NHLBI · UNIVERSITY OF ROCHESTER · PI BROOKES, PAUL S · 2003 to 2025
$7.7MPitx2 in atrial fibrillationR01HL118761 · NHLBI · BAYLOR COLLEGE OF MEDICINE · PI MARTIN, JAMES F · 2014 to 2025
$6.1MPathological flow-induced endothelial damage and plaque erosionR01HL149303 · NHLBI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI ABE, JUN-ICHI, COOKE, JOHN P · 2019 to 2022
$3.2MCytoskeletal Control of Yap in Heart RegenerationR01HL169511 · NHLBI · BAYLOR COLLEGE OF MEDICINE · PI James F Martin · 2023 to 2026
$2.7MMitigating radiation-induced cardiovascular disease by inhibiting premature agingU01AI156921 · NIAID · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI ABE, JUN-ICHI · 2020 to 2024
$2.5MA Novel Role for MAGI1 in regulating non-canonical LATS signaling and atherosclerotic plaque formationR01HL134740 · NHLBI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI LE, NHAT-TU · 2017 to 2021
$2.0MTissue Dependent Megakaryocyte FunctionsR01HL160610 · NHLBI · UNIVERSITY OF ROCHESTER · PI MORRELL, CRAIG N · 2022 to 2025
$2.0MReawakening cardiomyocyte proliferation from structural mediated quiescenceR01HL171574 · NHLBI · BAYLOR COLLEGE OF MEDICINE · PI James F Martin, Sean M Wu · 2024 to 2026
$1.9MLandscapes for Cell State Transition Leveraging by Single-Cell Multi-OmicsR35GM150460 · NIGMS · METHODIST HOSPITAL RESEARCH INSTITUTE · PI Guangyu Wang · 2023 to 2026
$1.6MHippo-YAP signaling in cardiac regenerative repairR01HL173242 · NHLBI · BAYLOR COLLEGE OF MEDICINE · PI James F Martin · 2025 to 2026
$1.4MSingle Cell Spatial Analysis in TissueR50CA243707 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI BURKS, JARED KYLE · 2020 to 2024
$1.3MNCI NIH HHS P30 CA016672NCI NIH HHS R50 CA243707NHLBI NIH HHS R01 HL071158NHLBI NIH HHS R01 HL118761NHLBI NIH HHS R01 HL134740NHLBI NIH HHS R01 HL149303NHLBI NIH HHS R01 HL160610NHLBI NIH HHS R01 HL169511NHLBI NIH HHS R01 HL171574NHLBI NIH HHS R01 HL173242NHLBI NIH HHS R01 HL177644NIAID NIH HHS U01 AI156921NIGMS NIH HHS R35 GM150460
Abstract
backgroundAtherothrombosis, which underlies most acute coronary syndromes and is driven by intraplaque thrombosis, preferentially occurs in regions of disturbed blood flow (d-flow). Although LATS1/2 (large tumor suppressor kinases 1 and 2) are known regulators of endothelial mechanotransduction, the mechanisms by which d-flow connects endothelial senescence, proliferation, and intraplaque thrombosis remain poorly understood.
methodsWe investigated endothelial cell (EC)-specific roles of
resultsTamoxifen-induced deletion of both Lats1 and Lats2 (homozygous) in ECs caused fatal edema and increased vascular permeability. In contrast,
conclusionsLoss of
Indexed as
ADP-ribosyl Cyclase 1Cellular SenescenceEndothelial CellsPlaque, AtheroscleroticProtein Serine-Threonine KinasesThrombosisTumor Suppressor ProteinsAnimalsCells, CulturedHumansMetabolic ReprogrammingMetabolomicsMiceMice, Inbred C57BLMice, KnockoutADP-ribosyl Cyclase 1LATS1 protein, humanLats1 protein, mouseLATS2 protein, humanLATS2 protein, mouseProtein Serine-Threonine KinasesTumor Suppressor Proteinsendothelial cellsmultiomicsproteomicsthrombosis
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