Identification of genes related to heart failure using global gene expression profiling of human failing myocardium

Min, Kyung‐Duk; Asakura, Masanori; Liao, Yulin; Nakamaru, Kenji; Okazaki, Hiroki; Takahashi, Tomoko; Fujimoto, Kazunori; Ito, Shin; Takahashi, Ayako; Asanuma, Hiroshi; Yamazaki, Satoru; Minamino, Tetsuo; Shoji, Shuichi; Seguchi, Osamu; Nakano, Atsushi; Ando, Yumiko; Otsuka, Toshiaki; Furukawa, Hidehiko; Isomura, Tadashi; Takashima, Seiji; Mochizuki, Naoki; Kitakaze, Masafumi

doi:10.1016/j.bbrc.2010.01.076

Cited by 98 publications

(119 citation statements)

References 18 publications

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“…However, because a GPR35 knockout line of mice has been reported to have markedly elevated blood pressure (Min et al, 2010), whereas blockade of acetic acid-induced writhing in mice has been shown to be limited by certain ligands, including pamoate (Zhao et al, 2010) and zaprinast (Cosi et al, 2011) that are reported to have agonist potency at GPR35, there are a developing number of supporting physiological studies. Despite this, to date only the studies of Min et al (2010) have used GPR35 knockout animals. This means that detailed pharmacological analysis of proposed ligands at GPR35 must be performed and understood with multiple species orthologs of the receptor before linking other potential physiological functions to the regulation of GPR35.…”

Section: Discussionmentioning

confidence: 99%

Antagonists of GPR35 Display High Species Ortholog Selectivity and Varying Modes of Action

Jenkins

Harries

Lappin

et al. 2012

J Pharmacol Exp Ther

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Variation in pharmacology and function of ligands at species orthologs can be a confounding feature in understanding the biology and role of poorly characterized receptors. Substantial selectivity in potency of a number of GPR35 agonists has previously been demonstrated between human and rat orthologs of this G protein-coupled receptor. Via a bioluminescence resonance energy transfer-based assay of induced interactions between GPR35 and ␤-arrestin-2, addition of the mouse ortholog to such studies indicated that, as for the rat ortholog, murine GPR35 displayed very low potency for pamoate, whereas potency for the reference GPR35 agonist zaprinast was intermediate between the rat and human orthologs. This pattern was replicated in receptor internalization and G protein activation assays. The effectiveness and mode of action of two recently reported GPR35 antagonists, methyl-5-[(tert-butylcarbamothioylhydrazinylidene)methyl]-1-(2,4-difluorophenyl)pyrazole-4-carboxylate (CID-2745687) and 2-hydroxy-4-[4-(5Z)-5-[(E)-2-methyl-3-phenylprop-2-enylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]butanoylamino)benzoic acid (ML-145), were investigated. Both CID-2745687 and ML-145 competitively inhibited the effects at human GPR35 of cromolyn disodium and zaprinast, two agonists that share an overlapping binding site. By contrast, although ML-145 also competitively antagonized the effects of pamoate, CID-2745687 acted in a noncompetitive fashion. Neither ML-145 nor CID-2745687 was able to effectively antagonize the agonist effects of either zaprinast or cromolyn disodium at either rodent ortholog of GPR35. These studies demonstrate that marked species selectivity of ligands at GPR35 is not restricted to agonists and considerable care is required to select appropriate ligands to explore the function of GPR35 in nonhuman cells and tissues.

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Section: Discussionmentioning

confidence: 99%

Antagonists of GPR35 Display High Species Ortholog Selectivity and Varying Modes of Action

Jenkins

Harries

Lappin

et al. 2012

J Pharmacol Exp Ther

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“…The poorly characterized G protein-coupled receptor (GPCR) GPR35 has been suggested as a potential target in conditions ranging from cardiovascular disease and metabolic disorders to inflammation and nociception (MacKenzie et al, 2011;Milligan, 2011,). These suggestions have arisen from studies exploring each of tissue distribution, functional studies, and genetic associations of GPR35 with disease (Leonard et al, 2005;Vander Molen et al, 2005;Wang et al, 2006;Min et al, 2010;Ellinghaus et al, 2012). However, understanding the biology of GPR35 has been restricted due to a paucity of high potency/affinity and selective ligands.…”

Section: Discussionmentioning

confidence: 99%

“…The class A orphan receptor GPR35 has been described as a potentially novel drug target (MacKenzie et al, 2011) based upon reports describing the activation of this receptor in a variety of cell types (Leonard et al, 2005;Wang et al, 2006;Ohshiro et al, 2008;Fallarini et al, 2010), the potential genetic linkage of GPR35 to disease (Shrimpton et al, 2004;Vander Molen et al, 2005;Ellinghaus et al, 2012), and the phenotypic profiling of a GPR35 knockout mouse line (Min et al, 2010). This has resulted in speculation that GPR35 may hold therapeutic potential for inflammatory disorders (Wang et al, 2006;Lattin et al, 2008;Barth et al, 2009), central nervous system function (Shrimpton et al, 2004;Lein et al, 2007;Guo et al, 2008), nociception (Ohshiro et al, 2008;Zhao et al, 2010;Cosi et al, 2011), metabolic disorders (Leonard et al, 2005;Vander Molen et al, 2005), hypertension, and cardiovascular disease (Sun et al, 2008;Min et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

“…This has resulted in speculation that GPR35 may hold therapeutic potential for inflammatory disorders (Wang et al, 2006;Lattin et al, 2008;Barth et al, 2009), central nervous system function (Shrimpton et al, 2004;Lein et al, 2007;Guo et al, 2008), nociception (Ohshiro et al, 2008;Zhao et al, 2010;Cosi et al, 2011), metabolic disorders (Leonard et al, 2005;Vander Molen et al, 2005), hypertension, and cardiovascular disease (Sun et al, 2008;Min et al, 2010). The physiologic and pathophysiologic functions of this receptor, however, remain to be fully determined (Milligan, 2011).…”

Section: Introductionmentioning

confidence: 99%

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High-Throughput Identification and Characterization of Novel, Species-selective GPR35 Agonists

Neetoo-Isseljee

Mackenzie

Southern

et al. 2012

J Pharmacol Exp Ther

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Drugs targeting the orphan receptor GPR35 have potential therapeutic application in a number of disease areas, including inflammation, metabolic disorders, nociception, and cardiovascular disease. Currently available surrogate GPR35 agonists identified from pharmacologically relevant compound libraries have limited utility due to the likelihood of off-target effects in vitro and in vivo and the variable potency that such ligands exhibit across species. We sought to identify and characterize novel GPR35 agonists to facilitate studies aimed at defining the physiologic role of GPR35. PathHunter b-arrestin recruitment technology was validated as a human GPR35 screening assay, and a high-throughput screen of 100,000 diverse low molecular weight compounds was conducted. Confirmed GPR35 agonists from five distinct chemotypes were selected for detailed characterization using both b-arrestin recruitment and G proteindependent assays and each of the human, mouse, and rat GPR35 orthologs. These studies identified 4-{(Z)-[(2Z)-2-(2-fluorobenzylidene)-4-oxo-1,3-thiazolidin-5-ylidene]methyl}benzoic acid (compound 1) as the highest potency full agonist of human GPR35 yet described. As with certain other GPR35 agonists, compound 1 was markedly selective for human GPR35, but displayed elements of signal bias between b-arrestin-2 and G protein-dependent assays. Compound 1 also displayed competitive behavior when assessed against the human GPR35 antagonist, ML-145 (2-hydroxy-4-[4-(5Z)-5-[(E)-2-methyl-3-phenylprop-2-enylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]butanoylamino]benzoic acid). Of the other chemotypes studied, compounds 2 and 3 were selective for the human receptor, but compounds 4 and 5 demonstrated similar activity at human, rat, and mouse GPR35 orthologs. Further characterization of these compounds and related analogs is likely to facilitate a better understanding of GPR35 in health and disease.

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“…The divergent gene expressions were identified which discriminated ischemic and non-ischemic cardiomyopathies conditions among the end-stage patients (Kittleson et al 2004; Kittleson et al 2005). Microarray analysis and gene expression profiling were used to discover genes related to heart failure using the expression profiles of 12 patients with heart failure (Min et al 2010), another study of normal controls and AMI patients discovered genetic markers and dysregulated pathways associated with disease recurrence in first time AMI patients (Suresh et al 2014). …”

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confidence: 99%

Diagnosis of coronary heart diseases using gene expression profiling; stable coronary artery disease, cardiac ischemia with and without myocardial necrosis

Kazmi

Gaunt

2015

Preprint

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Abstract-Cardiovascular disease including coronary artery disease and myocardial infarction is one of the leading causes of death in Europe, and is influenced by both environmental and genetic factors.With the advancements in genomic tools and technologies there is potential to predict and diagnose heart disease using molecular data from analysis of blood cells. We analyzed gene expression data from blood samples taken from normal people (n=21), non-significant coronary artery disease (n=93), patients with unstable angina (n=16), stable coronary artery disease (n=14) and myocardial infarction (MI; n=207). We used a feature selection approach to identify a set of gene expression variables which successfully differentiate different cardiovascular diseases. The initial features were discovered by fitting a linear model for each probe set across all arrays of normal individuals and patients with myocardial infarction. Three different feature optimisation algorithms were devised which identified two most discriminating sets of genes one using MI and normal controls (total genes=8) and another one using MI and unstable angina patients (total genes=17). The results proved the diagnostic robustness of the final feature sets in discriminating not only patients with myocardial infraction from healthy controls but also from patients with clinical symptoms of cardiac ischemia with myocardial necrosis and stable coronary artery disease despite the influence of batch effects and different microarray gene chips and platforms.

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Identification of genes related to heart failure using global gene expression profiling of human failing myocardium

Cited by 98 publications

References 18 publications

Antagonists of GPR35 Display High Species Ortholog Selectivity and Varying Modes of Action

Antagonists of GPR35 Display High Species Ortholog Selectivity and Varying Modes of Action

High-Throughput Identification and Characterization of Novel, Species-selective GPR35 Agonists

Diagnosis of coronary heart diseases using gene expression profiling; stable coronary artery disease, cardiac ischemia with and without myocardial necrosis

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