Interplay between inflammation and thrombosis in cardiovascular pathology

Nature Reviews Cardiology, Год журнала: 2021, Номер 18(9), С. 666 - 682

Опубликована: Май 6, 2021

Язык: Английский

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Tet2-Mediated Clonal Hematopoiesis Accelerates Heart Failure Through a Mechanism Involving the IL-1β/NLRP3 Inflammasome

Journal of the American College of Cardiology, Год журнала: 2018, Номер 71(8), С. 875 - 886

Опубликована: Фев. 1, 2018

Язык: Английский

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Monocyte-Macrophages and T Cells in Atherosclerosis

Immunity, Год журнала: 2017, Номер 47(4), С. 621 - 634

Опубликована: Окт. 1, 2017

Atherosclerosis is an arterial disease process characterized by the focal subendothelial accumulation of apolipoprotein-B-containing lipoproteins, immune and vascular wall cells, extracellular matrix. The lipoproteins acquire features damage-associated molecular patterns trigger first innate response, dominated monocyte-macrophages, then adaptive response. These inflammatory responses often become chronic non-resolving can lead to damage thrombosis-induced organ infarction. response regulated at various stages, from hematopoiesis monocyte changes macrophage activation. primarily mechanisms that affect balance between regulatory effector T cells. Mechanisms related cellular cholesterol, phenotypic plasticity, metabolism, aging play key roles in affecting these responses. Herein, we review select topics shed light on processes suggest new treatment strategies. Atherogenesis initiated entry retention (apoB LPs) into space, or "intima," regions disturbed blood flow medium-sized arteries (Williams Tabas, 1995Williams K.J. Tabas I. response-to-retention hypothesis early atherogenesis.Arterioscler. Thromb. Vasc. Biol. 1995; 15: 551-561Crossref PubMed Google Scholar, Fogelstrand Borén, 2012Fogelstrand P. Borén J. Retention atherogenic artery its role atherogenesis.Nutr. Metab. Cardiovasc. Dis. 2012; 22: 1-7Abstract Full Text PDF Scopus (0) Scholar). amount apoB LP determined concentration LPs blood, age metabolic state individual, genetic environmental factors. considerations biology, including variations proteoglycans retain factors alter endothelial permeability. Initially, some lipoprotein lipid internalized resident CD11c+ myeloid experimental depletion cells suppresses foam intracellular lipids (Paulson et al., 2010Paulson K.E. Zhu S.N. Chen M. Nurmohamed S. Jongstra-Bilen Cybulsky M.I. Resident intimal dendritic accumulate contribute initiation atherosclerosis.Circ. Res. 2010; 106: 383-390Crossref (169) Then, certain protein components LPs, particularly after oxidative modification, take properties (DAMPs) thereby (Glass Witztum, 2001Glass C.K. Witztum J.L. Atherosclerosis. road ahead.Cell. 2001; 104: 503-516Abstract (2166) Lusis, 2000Lusis A.J. Atherosclerosis.Nature. 2000; 407: 233-241Crossref (3547) This activates and, together with flow-mediated (Jongstra-Bilen 2006Jongstra-Bilen Haidari Guha D. Low-grade inflammation normal mouse intima predisposed atherosclerosis.J. Exp. Med. 2006; 203: 2073-2083Crossref (206) Gimbrone García-Cardeña, 2013Gimbrone Jr., M.A. García-Cardeña G. Vascular endothelium, hemodynamics, pathobiology atherosclerosis.Cardiovasc. Pathol. 2013; 9-15Abstract (109) promotes bone-marrow-derived monocytes (Tacke 2007Tacke F. Alvarez Kaplan T.J. Jakubzick C. Spanbroek R. Llodra Garin A. Liu Mack van Rooijen N. al.Monocyte subsets differentially employ CCR2, CCR5, CX3CR1 within atherosclerotic plaques.J. Clin. Invest. 2007; 117: 185-194Crossref (741) Swirski 2016Swirski F.K. Robbins C.S. Nahrendorf Development function cardiac macrophages.Trends Immunol. 2016; 37: 32-40Abstract Ly6Chi subpopulation differentiates macrophages, which, progressing lesions, phenotype 2007Swirski Libby Aikawa E. Alcaide Luscinskas F.W. Weissleder Pittet M.J. Ly-6Chi dominate hypercholesterolemia-associated monocytosis give rise macrophages atheromata.J. 195-205Crossref (698) In part as a result cell (DC) activation, involving helper 1 (Th1) but also Th17 Th2 B develops conjunction progressive decrease (Treg) (Witztum Lichtman, 2014Witztum Lichtman A.H. influence atherosclerosis.Annu. Rev. 2014; 9: 73-102Crossref (89) Other neutrophils platelet-neutrophil aggregates, natural killer mast eosinophils, are present human atheroma have been shown promote atherosclerosis via additional models Accompanying this reaction myofibroblasts intima; arise medial smooth muscle other sources referred (VSMCs) (Bennett 2016Bennett M.R. Sinha Owens G.K. Smooth Muscle Cells Atherosclerosis.Circ. 118: 692-702Crossref (139) rich matrix, which most likely represents "scar" ongoing injury. physiologic post-inflammatory secrete molecules carry out functions dampen tissue repair (Serhan 2007Serhan C.N. Brain S.D. Buckley C.D. Gilroy D.W. Haslett O'Neill L.A. Perretti Rossi A.G. Wallace Resolution inflammation: art, definitions terms.FASEB 21: 325-332Crossref (592) Nathan Ding, 2010Nathan Ding Nonresolving inflammation.Cell. 140: 871-882Abstract (751) However, will be explained later review, so-called resolution go awry setting atherosclerosis. Impaired lesions leads sustained, non-resolving, maladaptive plaque progression humans, triggers acute thrombo-occlusive cardiovascular events (Merched 2008Merched Ko K. Gotlinger K.H. Serhan Chan L. Atherosclerosis: evidence for impairment governed specific mediators.FASEB 2008; 3595-3606Crossref (234) 2010Tabas Macrophage death defective atherosclerosis.Nat. 10: 36-46Crossref (514) Viola Soehnlein, 2015Viola Soehnlein O. - A matter unresolved inflammation.Semin. 2015; 27: 184-193Crossref pathological clinically dangerous plaques include large areas necrosis thinning overlying collagenous, fibrous, cap. When breach forms fibrous cap, exposed thrombogenic material lesion, occlusive thrombosis infarction ensue (Virmani 2002Virmani Burke A.P. Kolodgie F.D. Farb Vulnerable plaque: pathology unstable coronary lesions.J. Interv. Cardiol. 2002; 439-446Crossref Libby, 2013Libby syndromes their implications therapy.N. 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Disordered haematopoiesis athero-thrombosis.Eur. 1113-1121Crossref (16) context, recent studies provided fascinating insight relevant (Figure 1). sympathetic nervous system (SNS) came researchers sought explain why accelerates myocardial (MI). initially end inflammatory-resolution spectrum, discussed following paragraphs, (Swirski substantial portion originate spleen, becomes populated hematopoietic stem progenitor (HSPCs) carries extramedullary (Robbins 2012Robbins Chudnovskiy Rauch P.J. Figueiredo Iwamoto Gorbatov Etzrodt Weber G.F. Ueno al.Extramedullary generates Ly-6C(high) infiltrate lesions.Circulation. 125: 364-374Crossref (187) mechanism post-MI SNS-mediated release HSPCs bone marrow, seeding elevated hematopoiesis, increased monocytes, drive (Dutta 2012Dutta Courties Wei Leuschner Thompson B. Carlson A.L. Heidt al.Myocardial atherosclerosis.Nature. 487: 325-329Crossref (388) Further suggests stress-related known disease, such psychosocial stress, might work through similar (Heidt 2014Heidt Sager H.B. Dutta Zaltsman von Zur Muhlen Bode Fricchione G.L. Denninger al.Chronic variable stress cells.Nat. 20: 754-758Crossref (161) How concepts apply atherothrombotic remains area future study, view uncertainties (Hilgendorf Swirski, 2012Hilgendorf Making difference: heterogeneity disease.Curr. Atheroscler. Rep. 14: 450-459Crossref Hypercholesterolemia monocytosis, Scholar), cholesterol efflux effected targeting proteins exacerbate (Murphy Scholar) 2). responsible cholesterol-induced involves expansion Lin−cKit+Sca1+ marrow compartment Mechanistic revealed cholesterol-mediated plasma membrane cell-surface expression common β-subunit interleukin-3 (IL-3) granulocyte-monocyte colony-stimulating (GM-CSF) receptors sensing two HSPC growth factors, IL-3 GM-CSF (Yvan-Charvet 2010Yvan-Charvet Pagler Gautier E.L. Avagyan Siry R.L. Han Welch C.L. Wang Randolph G.J. Snoeck H.W. ATP-binding cassette transporters HDL suppress proliferation.Science. 328: 1689-1693Crossref (289) There hypercholesterolemia, presumably increasing content decreases Rb, tumor suppressor limits proliferation, increases cyclins B1, D1, E1 (Seijkens 2014Seijkens Hoeksema Beckers Smeets Meiler Levels Tjwa de Winther M.P. Lutgens Hypercholesterolemia-induced priming aggravates atherosclerosis.FASEB 28: 2202-2213Crossref (31) Interestingly, when normocholesterolemic recipient were transplanted either hypercholesterolemic donor origin showed proliferation 10 weeks data long-lived, cell-intrinsic effect hypercholesterolemia HSPCs, perhaps epigenetic HSPCs. Moreover, Ldlr−/− fed Western-type diet saturated fats, had received developed larger advanced lesions. increase was accompanied higher number lesional leukocytes derived overall granulocytes, taken advantage fact leukocytosis myeloproliferative (MPD) associated For example, loss-of-function polymorphism gene encoding signaling adaptor called LNK (SH2B3) both MPD (McMullin 2011McMullin M.F. Wu Percy Tong W. nonsynonymous idiopathic erythrocytosis.Am. Hematol. 2011; 86: 962-964Crossref Deloukas 2013Deloukas Kanoni Willenborg Farrall Assimes T.L. Ingelsson Saleheen Erdmann Goldstein B.A. al.CARDIoGRAMplusC4D ConsortiumDIAGRAM ConsortiumCARDIOGENICS ConsortiumMuTHER ConsortiumWellcome Trust Case Control ConsortiumLarge-scale association analysis identifies loci disease.Nat. Genet. 45: 25-33Crossref (712) somatic gain-of-function mutations JAK2 kinase (Viny Levine, 2014Viny A.D. Levine Genetics neoplasms.Cancer 61-65Crossref Although platelets association, there link monocytosis. Lnk Lnk−/−Ldlr−/− Western has found cause hypercholesterolemia-dependent amounts pro-atherogenic chemokine chemotactic protein-1 (MCP-1; CCL2) (Wang 2016Wang Tang Tascau Balcerek LNK/SH2B3 Loss Function Promotes Thrombosis.Circ. 119: e91-e103Crossref Most importantly, demonstrate lesion area, platelet-monocyte aggregates Synergy deficiency further IL-3-GM-CSF receptor emerges study showing Glut1-mediated glucose uptake myeloproliferation disorders (Gautier 2013Gautier Westerterp Bhagwat Cremers Shih Abdel-Wahab Lütjohann Yvan-Charvet Glut1 inhibition reverse hypermetabolic disorders.J. 210: 339-353Crossref (29) glycolysis (Van den Bossche 2017Van Menon immunometabolism: Where (going)?.Trends 395-406Abstract (32) authors propose provides energy necessary proliferation. Ly6Clo derive serve maintenance "patrolling" tissues increasingly unclear, it even whether they differentiate (Jakubzick 2017Jakubzick C.V. Henson P.M. differentiation antigen-presenting functions.Nat. 17: 349-362Crossref As such, poorly understood. one investigators tested nuclear Nr4a1 (Nur77), required survival (Hanna 2011Hanna R.N. Carlin L.M. Hubbeling H.G. Nackiewicz Green A.M. Punt J.A. Geissmann Hedrick C.C. transcription NR4A1 (Nur77) controls Ly6C- monocytes.Nat. 12: 778-785Crossref (221) Two Nr4a1—Western-diet-fed lacking Apoe−/− germline Nr4a1—demonstrated atherosclerosis, proportion resolving interpretation finding directly regulate another possible conversion 2014Hilgendorf Gerhardt Tan T.C. Winter Holderried T.A. Chousterman B.G. Liao Zirlik Scherer-Crosbie al.Ly-6Chigh depend reparative phases infarcted myocardium.Circ. 114: 1611-1622Crossref (142) immediately MI then, during phase, properties. Nr4a1, infiltrating highly unable repair. If applicable Nr4a1-deficient could Ly6hi Nr4a1-dependent manner. Consistent idea, source regression (Rahman 2017Rahman Vengrenyuk Ramsey S.A. Vila N.R. Girgis N.M. Gusarova V. Gromada Weinstock Moore al.Inflammatory M2 regression.J. 127: 2904-2915Crossref vary widely depending interacting variables local environment ("tissue niche") (Gosselin 2014Gosselin Link V.M. Romanoski C.E. Fonseca Eichenfield D.Z. Spann N.J. Stender J.D. Chun Garner H. Glass Environment drives selection enhancers controlling tissue-specific identities.Cell. 159: 1327-1340Abstract (332) Lavin 2014Lavin Blecher-Gonen David Keren-Shaul Merad Jung Amit Tissue-resident enhancer landscapes shaped microenvironment.Cell. 1312-1326Abstract (466) metabolism gut microbiota metabolites 2011Wang Z. Klipfell Bennett B.J. Koeth Levison B.S. Dugar Feldstein A.E. Britt E.B. Fu X. Chung Y.M. al.Gut flora phosphatidylcholine disease.Nature. 472: 57-63Crossref (1453) non-coding RNAs (Erbilgin 2013Erbilgin Civelek Pan Hagopian Berliner Lusis Identification CAD candidate genes GWAS cells.J. Lipid 54: 1894-1905Crossref (42) 2015Chen H.H. Keyhanian Zhou Vilmundarson R.O. Almontashiri N.A. Cruz Pandey Lerma Yap Ho Stewart C.A. al.IRF2BP2 reduces susceptibility 671-683Crossref (8) 2016Wu X.Q. Dai Yang Huang Meng X.M. B.M. Li Emerging microRNAs regulating activation polarization inflammation.Immunology. 148: 237-248Crossref (23) 2016Amit D.R. epigenetics shaping identity homeostasis.Nat. 18-25Crossref (71) Phan 2017Phan A.T. Goldrath A.W. Metabolic coordination immunity.Immunity. 46: 714-729Abstract Aryal 2014Aryal Rotllan Fernández-Hernando Noncoding atherosclerosis.Curr. 16: 407Crossref program spectrum host defense general, progression, whereas (Peled Fisher, 2014Peled Fisher E.A. Dynamic aspects regression.Front. 5: 579Crossref (50) By secreting cytokines, proteases, morphological rupture lumenal thrombosis. protective collagenous scar (fibrous cap). Conversely, stabilization. clearing dead (efferocytosis), stabilize preventing post-apoptotic necrosis; collagen form over lesion; producing quell Molecular profiling stages demonstrated suggestive different One using immunohistochemistry RNA CD68+ ends inflammation-resolution develop (Stöger 2012Stöger Gijbels der Velden Manca Loos C.M. Biessen Daemen Distribution markers ather

Язык: Английский

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Modulation of the interleukin-6 signalling pathway and incidence rates of atherosclerotic events and all-cause mortality: analyses from the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS)

European Heart Journal, Год журнала: 2018, Номер 39(38), С. 3499 - 3507

Опубликована: Май 16, 2018

Canakinumab, a monoclonal antibody targeting interleukin (IL)-1β, reduces rates of recurrent cardiovascular events without lowering lipids. It is uncertain, however, to what extent these beneficial outcomes are mediated through interleukin-6 (IL-6) signalling, an issue with substantial pathophysiologic consequences and therapeutic implications.A total 4833 stable atherosclerosis patients in the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS) had IL-6 levels measured before randomization after treatment placebo or one three doses canakinumab (50 mg, 150 300 mg) given subcutaneously once every 3 months. Participants were followed for up 5 years (median follow-up 3.7 years). Compared those allocated placebo, CANTOS participants receiving who achieved on-treatment below study median value 1.65 ng/L experienced 32% reduction major adverse [MACE, multivariable adjusted hazard ratio (HRadj) 0.68, 95% confidence interval (CI) 0.56-0.82; P < 0.0001], 30% MACE plus additional endpoint hospitalization unstable angina requiring urgent revascularization (MACE+, HRadj 0.70, CI 0.59-0.84; 0.0001), 52% mortality (HRadj 0.48, 0.34-0.68; 48% all-cause 0.52, 0.40-0.68; 0.0001) prolonged treatment. In contrast, equal above taking first dose no significant benefit any endpoints. These differential findings based on magnitude response seen analyses alternatively tertiles levels, using statistical inference approach estimate effect among individuals would achieve targeted level.CANTOS provides proof concept evidence humans that modulation signalling pathway, at least canakinumab, associates reduced event rates, independent lipid lowering.ClinicalTrials.gov NCT01327846.

Язык: Английский

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The roles of DNA, RNA and histone methylation in ageing and cancer

Nature Reviews Molecular Cell Biology, Год журнала: 2019, Номер 20(10), С. 573 - 589

Опубликована: Июль 3, 2019

Язык: Английский

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Neutrophils as regulators of cardiovascular inflammation

Nature Reviews Cardiology, Год журнала: 2020, Номер 17(6), С. 327 - 340

Опубликована: Янв. 29, 2020

Язык: Английский

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Clonal Hematopoiesis and Evolution to Hematopoietic Malignancies

Cell stem cell, Год журнала: 2018, Номер 22(2), С. 157 - 170

Опубликована: Фев. 1, 2018

Язык: Английский

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Association of Mutations Contributing to Clonal Hematopoiesis With Prognosis in Chronic Ischemic Heart Failure

JAMA Cardiology, Год журнала: 2018, Номер 4(1), С. 25 - 25

Опубликована: Дек. 19, 2018

Importance

Somatic mutations causing clonal expansion of hematopoietic cells (clonal hematopoiesis indeterminate potential [CHIP]) are increased with age and associated atherosclerosis inflammation. Age inflammation the major risk factors for heart failure, yet association CHIP failure in humans is unknown.

Objective

To assess prognostic significance patients chronic (CHF) owing to ischemic origin.

Design, Setting, Participants

We analyzed bone marrow–derived mononuclear from 200 CHF by deep targeted amplicon sequencing detect presence such long-term prognosis at University Hospital Frankfurt, Germany. Data were between October 2017 April 2018.

Results

Median was 65 years. Forty-seven a variant allele fraction (VAF) least 0.02 found 38 (18.5%). The somatic most commonly occurred genesDNMT3A(14 patients),TET2(9 patients),KDM6A(4 patients), andBCOR(3 patients). Patients older more frequently had history hypertension. During median follow-up 4.4 years, total 53 died, 23 required hospitalization failure. There significantly worse clinical outcome eitherDNMT3AorTET2mutations compared non-CHIP carriers. By multivariable Cox proportional regression analysis, withinTET2orDNMT3A(HR, 2.1; 95% CI, 1.1-4.0;P = .02, death combined hospitalization) (HR, 1.04; 1.01-1.07 per year;P .005) but not hypertension remained independently adverse outcome. Importantly, there significant dose-response VAF

Conclusions Relevance

Our data suggest that cells, specifically mutated driver genesTET2andDNMT3A, may be progression poor CHF. Future studies will have validate our findings larger cohorts address whether targeting specific inflammatory pathways valuable precision medicine carrying encoding CHIP.

Язык: Английский

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Anemia at older age: etiologies, clinical implications, and management

Blood, Год журнала: 2017, Номер 131(5), С. 505 - 514

Опубликована: Ноя. 15, 2017

Язык: Английский

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Bone marrow niches in haematological malignancies

Nature reviews. Cancer, Год журнала: 2020, Номер 20(5), С. 285 - 298

Опубликована: Фев. 28, 2020

Язык: Английский

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