Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tissue renin-angiotensin-aldosterone system (RAAS) has attracted much attention because of its physiological and pharmacological implications; however, a clear definition of tissue RAAS is still missing. We aimed to establish a preliminary atlas for the organization of RAAS across 23 different normal human tissues. A set of 37 genes encoding classical and novel RAAS participants including gluco- and mineralo-corticoids were defined as extended RAAS (extRAAS) system. Microarray data sets containing more than 10 normal tissues were downloaded from the GEO database. R software was used to extract expression levels and construct dendrograms of extRAAS genes within each data set. Tissue co-expression modules were then extracted from reproducible gene clusters across data sets. An atlas of the maps of tissue-specific organization of extRAAS was constructed from gene expression and coordination data. Our analysis included 143 data sets containing 4933 samples representing 23 different tissues. Expression data provided an insight on the favored pathways in a given tissue. Gene coordination indicated the existence of tissue-specific modules organized or not around conserved core groups of transcripts. The atlas of tissue-specific organization of extRAAS will help better understand tissue-specific effects of RAAS. This will provide a frame for developing more effective and selective pharmaceuticals targeting extRAAS.
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PMID:Atlas of tissue renin-angiotensin-aldosterone system in human: A transcriptomic meta-analysis. 2599 67

Despite the well-known role of the renin-angiotensin-aldosterone system (RAAS) in atheroma, its global local organization is poorly understood. In this study, we used transcriptomic meta-analysis to reveal the local transcriptional organization and regulation of 37 extended RAAS (extRAAS) genes in atheroma. Expression analysis and hierarchical clustering were done on extRAAS genes in 32 paired early and advanced atherosclerotic lesions. Contrary to receptor-coding transcripts, multiple angiotensin-metabolizing enzymes showed higher expression in advance, in comparison to early lesions. Interestingly, similar results were obtained from GEO data sets containing human (n=839) and mouse (n=18) atherosclerotic samples, but different from normal human (n=11) arterial tissues. The expression and coordination patterns were then used to construct transcriptional maps of extRAAS, displaying favored pathways in atheroma. Three coexpression modules (M1, M2, and M3) with >80% reproducibility across human atheroma data sets were identified. M1 and M3 contained angiotensin-metabolizing enzymes transcripts, whereas M2 contained proatherogenic receptor-coding transcripts. Interestingly, M1 and M2 were negatively correlated. A total of 21 transcription factors with enriched binding sites in the promoters of coordinated genes were extracted, among which IRF5, MAX, and ETV5 showed significant positive correlations with M1, but negative correlations with M2. However, ETS1 and SMAD1 transcripts were positively correlated to receptor-coding genes in M2. Despite sharing some similarities in extRAAS organization with kidney and adipose, atheroma showed specific correlations between extRAAS and transcription factors. In conclusion, our transcriptional map helps in designing more efficient treatments for atherosclerosis. In addition, the identified transcription factors provide a basis for the discovery of atheroma-specific modulators of extRAAS.
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PMID:Transcriptomic Analysis Reveals Novel Transcription Factors Associated With Renin-Angiotensin-Aldosterone System in Human Atheroma. 2775 66