Department of Internal Medicine, Division of Cardiology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Texas Heart Institute at Baylor St. Luke's Medical Center, Houston, TX 77030, USA.
Int J Mol Sci. 2023 Sep 5;24(18):13709. doi: 10.3390/ijms241813709.
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 ( = 18) and non-failing heart samples ( = 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.
G 蛋白偶联受体 (GPCR) 是心脏生理学的关键调节剂，也是治疗心脏病的重要治疗靶点。异位嗅觉受体 (OR) 是在鼻外组织中表达的 GPCR，它们最近作为心脏功能代谢控制的新介质出现。本研究的目的是描绘人心脏中的 OR 基因表达谱，鉴定由缺血性心肌病引起的心力衰竭中失调的 OR，并提供证据表明这些改变的 OR 在心力衰竭发病机制中的作用。来自心力衰竭患者 (= 18)和非衰竭心脏样本 (= 4)的左心室组织进行了两步转录组分析，包括实时 PCR 阵列上 372 种不同 OR 转录本的定量和通过 RNA 测序同时确定全局心脏基因表达。该策略确定了 >160 种在人心脏中表达的 OR，包括 38 种与心力衰竭失调的受体。共表达分析预测失调的 OR 参与线粒体功能、细胞外基质重塑和炎症的改变。我们提供这个数据集作为研究 OR 在人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。
