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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Marques , F Z , Prestes , P R , Byars , S G , Ritchie , S C , Wurtz , 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 , Kahonen , M , Lehtimaki , 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 2017 , ' Experimental and Human Evidence for Lipocalin-2 (Neutrophil Gelatinase-Associated Lipocalin [NGAL]) in the Development of Cardiac Hypertrophy and heart failure ' , Journal of the American Heart Association , vol. 6 , no. 6 , 005971 . https://doi.org/10.1161/JAHA.117.005971

Title: Experimental and Human Evidence for Lipocalin-2 (Neutrophil Gelatinase-Associated Lipocalin [NGAL]) in the Development of Cardiac Hypertrophy and heart failure
Author: Marques, Francine Z.; Prestes, Priscilla R.; Byars, Sean G.; Ritchie, Scott C.; Wurtz, Peter; Patel, Sheila K.; Booth, Scott A.; Rana, Indrajeetsinh; Minoda, Yosuke; Berzins, Stuart P.; Curl, Claire L.; Bell, James R.; Wai, Bryan; Srivastava, Piyush M.; Kangas, Antti J.; Soininen, Pasi; Ruohonen, Saku; Kahonen, Mika; Lehtimaki, Terho; Raitoharju, Emma; Havulinna, Aki; Perola, Markus; Raitakari, Olli; Salomaa, Veikko; Ala-Korpela, Mika; Kettunen, Johannes; McGlynn, Maree; Kelly, Jason; Wlodek, Mary E.; Lewandowski, Paul A.; Delbridge, Lea M.; Burrell, Louise M.; Inouye, Michael; Harrap, Stephen B.; Charchar, Fadi J.
Contributor: University of Helsinki, Complex Disease Genetics
University of Helsinki, Institute for Molecular Medicine Finland
Date: 2017-06
Language: eng
Number of pages: 57
Belongs to series: Journal of the American Heart Association
ISSN: 2047-9980
URI: http://hdl.handle.net/10138/203757
Abstract: 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.
Subject: concentric hypertrophy
C-reactive protein
gene coexpression networks
GlycA
hypertrophy
lipocalin-2
NGAL
systems biology
DIFFERENTIAL EXPRESSION ANALYSIS
LEFT-VENTRICULAR HYPERTROPHY
CARDIOVASCULAR RISK
INSULIN-RESISTANCE
YOUNG FINNS
SYSTEMIC INFLAMMATION
GROWTH RESTRICTION
MIR-15 FAMILY
R PACKAGE
DISEASE
3121 General medicine, internal medicine and other clinical medicine
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