A Two-Step Transcriptome Analysis of the Human Heart Reveals Broad and Disease-Responsive Expression of Ectopic Olfactory Receptors.
A Two-Step Transcriptome Analysis of the Human Heart Reveals Broad and Disease-Responsive Expression of Ectopic Olfactory Receptors.
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DOI：
10.3390/ijms241813709
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发表时间：
2023-09-05
影响因子：
5.6
通讯作者：
Harmancey R
中科院分区：
文献类型：
--
作者：
Ashraf S;Frazier OH;Carranza S;McPherson DD;Taegtmeyer H;Harmancey R
g蛋白偶联受体（gpcr）是心脏生理的重要调节因子，也是治疗心脏病的关键治疗靶点。异位嗅觉受体（ORs）是一种表达于鼻外组织的GPCRs，近年来作为一种新的心功能代谢控制介质而出现。本研究的目的是分析人类心脏中OR基因的表达，识别因缺血性心肌病引起的心力衰竭而失调的OR，并为这些改变的OR在心力衰竭发病机制中的作用提供证据。来自心力衰竭患者（n = 18）和非衰竭心脏样本（n = 4）的左心室组织进行了两步转录组分析，包括通过实时PCR阵列定量分析372个不同的OR转录本，同时通过RNA测序测定全局心脏基因表达。这一策略鉴定出了在人类心脏中表达的bbbb160 or，包括38个与心力衰竭有差异调节的受体。共表达分析预测了ORs失调与线粒体功能改变、细胞外基质重塑和炎症的关系。我们提供这个数据集作为研究ORs在人类心脏中的作用的资源，希望它将有助于确定治疗心力衰竭的新治疗靶点。
G-protein-coupled receptors (GPCRs) are critical regulators of cardiac physiology and a key therapeutic target for the treatment of heart disease. Ectopic olfactory receptors (ORs) are GPCRs expressed in extra-nasal tissues which have recently emerged as new mediators in the metabolic control of cardiac function. The goals of this study were to profile OR gene expression in the human heart, to identify ORs dysregulated by heart failure caused by ischemic cardiomyopathy, and to provide evidence suggestive of a role for those altered ORs in the pathogenesis of heart failure. Left ventricular tissue from heart failure patients (n = 18) and non-failing heart samples (n = 4) were subjected to a two-step transcriptome analysis consisting of the quantification of 372 distinct OR transcripts on real-time PCR arrays and simultaneous determination of global cardiac gene expression by RNA sequencing. This strategy led to the identification of >160 ORs expressed in the human heart, including 38 receptors differentially regulated with heart failure. Co-expression analyses predicted the involvement of dysregulated ORs in the alteration of mitochondrial function, extracellular matrix remodeling, and inflammation. We provide this dataset as a resource for investigating roles of ORs in the human heart, with the hope that it will assist in the identification of new therapeutic targets for the treatment of heart failure.
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DOI：
10.1021/acs.jpclett.8b00633
发表时间：
2018-05-03
期刊：
The journal of physical chemistry letters
影响因子：
--
作者：
Bushdid C;de March CA;Fiorucci S;Matsunami H;Golebiowski J
通讯作者：
Golebiowski J
影响因子：
10.7
作者：
De la Cruz, Omar;Blekhman, Ran;Gilad, Yoav
通讯作者：
Gilad, Yoav
影响因子：
8.3
作者：
Bragazzi, Nicola Luigi;Zhong, Wen;Dai, Haijiang
通讯作者：
Dai, Haijiang
影响因子：
64.5
作者：
Malnic, B;Hirono, J;Buck, LB
通讯作者：
Buck, LB
影响因子：
5.4
作者：
Ramirez Flores RO;Lanzer JD;Holland CH;Leuschner F;Most P;Schultz JH;Levinson RT;Saez-Rodriguez J
通讯作者：
Saez-Rodriguez J