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Experimental and Human Evidence for Lipocalin-2 (Neutrophil Gelatinase-Associated Lipocalin [NGAL]) in the Development of Cardiac Hypertrophy and heart failure
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نویسنده
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marques f.z. ,prestes p.r. ,byars s.g. ,ritchie s.c. ,würtz p. ,patel s.k. ,booth s.a. ,rana i. ,minoda y. ,berzins s.p. ,curl c.l. ,bell j.r. ,wai b. ,srivastava p.m. ,kangas a.j. ,soininen p. ,ruohonen s. ,kähönen m. ,lehtimäki t. ,raitoharju e. ,havulinna a. ,perola m. ,raitakari o. ,salomaa v. ,ala-korpela m. ,kettunen j. ,mcglynn m. ,kelly j. ,wlodek m.e. ,lewandowski p.a. ,delbridge l.m. ,burrell l.m. ,inouye m. ,harrap s.b. ,charchar f.j.
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منبع
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journal of the american heart association - 2017 - دوره : 6 - شماره : 6
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چکیده
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Background: cardiac hypertrophy increases the risk of developing heart failure and cardiovascular death. the neutrophil inflammatory protein,lipocalin-2 (lcn2/ngal),is elevated in certain forms of cardiac hypertrophy and acute heart failure. however,a specific role for lcn2 in predisposition and etiology of hypertrophy and the relevant genetic determinants are unclear. here,we defined the role of lcn2 in concentric cardiac hypertrophy in terms of pathophysiology,inflammatory expression networks,and genomic determinants.methods and results: we used 3 experimental models: a polygenic model of cardiac hypertrophy and heart failure,a model of intrauterine growth restriction and lcn2-knockout mouse; cultured cardiomyocytes; and 2 human cohorts: 114 type 2 diabetes mellitus patients and 2064 healthy subjects of the yfs (young finns study). in hypertrophic heart rats,cardiac and circulating lcn2 was significantly overexpressed before,during,and after development of cardiac hypertrophy and heart failure. lcn2 expression was increased in hypertrophic hearts in a model of intrauterine growth restriction,whereas lcn2-knockout mice had smaller hearts. in cultured cardiomyocytes,lcn2 activated molecular hypertrophic pathways and increased cell size,but reduced proliferation and cell numbers. increased lcn2 was associated with cardiac hypertrophy and diastolic dysfunction in diabetes mellitus. in the yfs,lcn2 expression was associated with body mass index and cardiac mass and with levels of inflammatory markers. the single-nucleotide polymorphism,rs13297295,located near lcn2 defined a significant cis-eqtl for lcn2 expression.conclusions: direct effects of lcn2 on cardiomyocyte size and number and the consistent associations in experimental and human analyses reveal a central role for lcn2 in the ontogeny of cardiac hypertrophy and heart failure. © 2017 the authors. published on behalf of the american heart association,inc.,by wiley.
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کلیدواژه
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concentric hypertrophy; C‐reactive protein; gene coexpression networks; GlycA; hypertrophy; lipocalin‐2; NGAL; systems biology
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آدرس
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school of applied and biomedical sciences,faculty of science and technology,federation university australia,ballarat,victoria,australia,heart failure research group,baker heart and diabetes research institute,melbourne,victoria, Australia, school of applied and biomedical sciences,faculty of science and technology,federation university australia,ballarat,victoria, Australia, centre for systems genomics,the university of melbourne,victoria,australia,school of biosciences,the university of melbourne,victoria,australia,department of pathology,the university of melbourne,victoria, Australia, centre for systems genomics,the university of melbourne,victoria,australia,department of pathology,the university of melbourne,victoria, Australia, computational medicine,faculty of medicine,university of oulu and biocenter oulu,oulu, Finland, department of medicine,the university of melbourne austin health,heidelberg,victoria, Australia, school of applied and biomedical sciences,faculty of science and technology,federation university australia,ballarat,victoria, Australia, school of applied and biomedical sciences,faculty of science and technology,federation university australia,ballarat,victoria, Australia, school of applied and biomedical sciences,faculty of science and technology,federation university australia,ballarat,victoria, Australia, school of applied and biomedical sciences,faculty of science and technology,federation university australia,ballarat,victoria,australia,department of microbiology and immunology,peter doherty institute,the university of melbourne,victoria, Australia, department of physiology,the university of melbourne,victoria, Australia, department of physiology,the university of melbourne,victoria, Australia, department of medicine,the university of melbourne austin health,heidelberg,victoria,australia,department of cardiology,austin health,heidelberg,victoria, Australia, department of medicine,the university of melbourne austin health,heidelberg,victoria,australia,department of cardiology,austin health,heidelberg,victoria, Australia, computational medicine,faculty of medicine,university of oulu and biocenter oulu,oulu, Finland, computational medicine,faculty of medicine,university of oulu and biocenter oulu,oulu,finland,nmr metabolomics laboratory,school of pharmacy,university of eastern finland,kuopio, Finland, research centre of applied and preventive cardiovascular medicine,university of turku, Finland, department of clinical physiology,university of tampere and tampere university hospital,tampere, Finland, fimlab laboratories,department of clinical chemistry,pirkanmaa hospital district,school of medicine,university of tampere, Finland, fimlab laboratories,department of clinical chemistry,pirkanmaa hospital district,school of medicine,university of tampere, Finland, national institute for health and welfare,helsinki, Finland, national institute for health and welfare,helsinki,finland,institute for molecular medicine finland,university of helsinki, Finland, research centre of applied and preventive cardiovascular medicine,university of turku,finland,department of clinical physiology and nuclear medicine,turku university hospital,turku, Finland, national institute for health and welfare,helsinki, Finland, computational medicine,faculty of medicine,university of oulu and biocenter oulu,oulu,finland,nmr metabolomics laboratory,school of pharmacy,university of eastern finland,kuopio,finland,medical research council integrative epidemiology unit,university of bristol,united kingdom,school of social and community medicine,university of bristol, United Kingdom, computational medicine,faculty of medicine,university of oulu and biocenter oulu,oulu,finland,nmr metabolomics laboratory,school of pharmacy,university of eastern finland,kuopio,finland,national institute for health and welfare,helsinki, Finland, school of medicine,deakin university,waurn ponds,victoria, Australia, school of applied and biomedical sciences,faculty of science and technology,federation university australia,ballarat,victoria, Australia, department of medicine,the university of melbourne austin health,heidelberg,victoria, Australia, school of medicine,deakin university,waurn ponds,victoria, Australia, department of physiology,the university of melbourne,victoria, Australia, department of medicine,the university of melbourne austin health,heidelberg,victoria,australia,department of cardiology,austin health,heidelberg,victoria, Australia, heart failure research group,baker heart and diabetes research institute,melbourne,victoria,australia,centre for systems genomics,the university of melbourne,victoria,australia,school of biosciences,the university of melbourne,victoria,australia,department of pathology,the university of melbourne,victoria,australia,department of physiology,the university of melbourne,victoria, Australia, department of physiology,the university of melbourne,victoria, Australia, school of applied and biomedical sciences,faculty of science and technology,federation university australia,ballarat,victoria,australia,department of physiology,the university of melbourne,victoria,australia,department of cardiovascular sciences,university of leicester, United Kingdom
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Authors
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