title: Identification of genes related to heart failure using global gene expression profiling of human failing myocardium.
abstract: Although various management methods have been developed for heart failure, it is necessary to investigate the diagnostic or therapeutic targets of heart failure. Accordingly, we have developed different approaches for managing heart failure by using conventional microarray analyses. We analyzed gene expression profiles of myocardial samples from 12 patients with heart failure and constructed datasets of heart failure-associated genes using clinical parameters such as pulmonary artery pressure (PAP) and ejection fraction (EF). From these 12 genes, we selected four genes with high expression levels in the heart, and examined their novelty by performing a literature-based search. In addition, we included four G-protein-coupled receptor (GPCR)-encoding genes, three enzyme-encoding genes, and one ion-channel protein-encoding gene to identify a drug target for heart failure using in silico microarray database. After the in vitro functional screening using adenovirus transfections of 12 genes into rat cardiomyocytes, we generated gene-targeting mice of five candidate genes, namely, MYLK3, GPR37L1, GPR35, MMP23, and NBC1. The results revealed that systolic blood pressure differed significantly between GPR35-KO and GPR35-WT mice as well as between GPR37L1-Tg and GPR37L1-KO mice. Further, the heart weight/body weight ratio between MYLK3-Tg and MYLK3-WT mice and between GPR37L1-Tg and GPR37L1-KO mice differed significantly. Hence, microarray analysis combined with clinical parameters can be an effective method to identify novel therapeutic targets for the prevention or management of heart failure.
authors.affiliation: Department of Cardiovascular Medicine, Osaka, Japan.
authors.forename: Kyung-Duk
authors.initials: KD
authors.lastname: Min
authors.forename: Masanori
authors.initials: M
authors.lastname: Asakura
authors.forename: Yulin
authors.initials: Y
authors.lastname: Liao
authors.forename: Kenji
authors.initials: K
authors.lastname: Nakamaru
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Okazaki
authors.forename: Tomoko
authors.initials: T
authors.lastname: Takahashi
authors.forename: Kazunori
authors.initials: K
authors.lastname: Fujimoto
authors.forename: Shin
authors.initials: S
authors.lastname: Ito
authors.forename: Ayako
authors.initials: A
authors.lastname: Takahashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Asanuma
authors.forename: Satoru
authors.initials: S
authors.lastname: Yamazaki
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Minamino
authors.forename: Shoji
authors.initials: S
authors.lastname: Sanada
authors.forename: Osamu
authors.initials: O
authors.lastname: Seguchi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nakano
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Ando
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Otsuka
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Furukawa
authors.forename: Tadashi
authors.initials: T
authors.lastname: Isomura
authors.forename: Seiji
authors.initials: S
authors.lastname: Takashima
authors.forename: Naoki
authors.initials: N
authors.lastname: Mochizuki
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kitakaze
mesh_terms: D000256:Adenoviridae; D000368:Aged; D000818:Animals; D002478:Cells, Cultured; D005260:Female; D020869:Gene Expression Profiling; D006333:Heart Failure / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D051381:Rats