Arteriosclerosis, thrombosis, and vascular biology, 2014-04, Vol.34 (4), p.902-912
2014
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- Autor(en) / Beteiligte
- Titel
- Tissue-specific RNA-Seq in human evoked inflammation identifies blood and adipose LincRNA signatures of cardiometabolic diseases
- Ist Teil von
- Arteriosclerosis, thrombosis, and vascular biology, 2014-04, Vol.34 (4), p.902-912
- Ort / Verlag
- United States
- Erscheinungsjahr
- 2014
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Inappropriate transcriptional activation of innate immunity is a pathological feature of several cardiometabolic disorders, but little is known about inflammatory modulation of long intergenic noncoding RNAs (lincRNAs) in disease-relevant human tissues. We applied deep RNA sequencing (>500 million filtered reads per sample) to blood and adipose during low-dose experimental endotoxemia (lipopolysaccharide) in a healthy human, with targeted replication in separate individuals undergoing endotoxemia (n=6), to identify inflammatory lincRNAs. A subset of these lincRNAs was examined for expression in adipocytes and monocytes, modulation in adipose of obese humans, and overlap with genome-wide association study signals for inflammatory and cardiometabolic traits. Of a stringent set of 4284 lincRNAs, ≈11% to 22% were expressed with 201 and 56 lincRNAs modulated by lipopolysaccharide in blood or adipose, respectively. Tissue-specific expression of a subset of 6 lipopolysaccharide-lincRNAs was replicated with lipopolysaccharide modulation confirmed for all 3 expressed in blood and 2 of 4 expressed in adipose. The broader generalizability of findings in blood of subject A was confirmed by RNA sequencing in 7 additional subjects. We confirmed adipocytes and monocytes as potential cell-sources of selective lipopolysaccharide-regulated lincRNAs, and 2 of these, linc-DMRT2 (P=0.002) and linc-TP53I13 (P=0.01), were suppressed in adipose of obese humans. Finally, we provide examples of lipopolysaccharide-modulated lincRNAs that overlap single nucleotide polymorphisms that are associated with cardiometabolic traits. Our findings provide novel insights into tissue-level, inflammatory transcriptome regulation in cardiometabolic diseases. These are complementary to more usual approaches limited to interrogation of DNA variations.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1079-5642eISSN: 1524-4636DOI: 10.1161/atvbaha.113.303123Titel-ID: cdi_pubmed_primary_24504737
- Format
- –
- Schlagworte
- Adipocytes - metabolism, Adult, Binding Sites, Case-Control Studies, Cells, Cultured, Endotoxemia - blood, Endotoxemia - genetics, Female, Gene Expression Profiling - methods, Gene Expression Regulation, Genetic Markers, Genome-Wide Association Study, High-Throughput Nucleotide Sequencing, Humans, Inflammation - blood, Inflammation - genetics, Inflammation Mediators - blood, Lipopolysaccharides - pharmacology, Male, Metabolic Syndrome - blood, Metabolic Syndrome - genetics, Monocytes - metabolism, Obesity - blood, Obesity - genetics, Reproducibility of Results, RNA, Long Noncoding - blood, Sequence Analysis, RNA - methods, Subcutaneous Fat - drug effects, Subcutaneous Fat - metabolism, Transcription Factors - metabolism, Young Adult