Characterization of Levels and Cellular Transfer of Circulating Lipoprotein-Bound MicroRNAs

Wagner, Jasmin; Riwanto, Meliana; Besler, Christian; Knau, Andrea; Fichtlscherer, Stephan; Röxe, Tino; Zeiher, Andreas M.; Landmesser, Ulf; Dimmeler, Stefanie

doi:10.1161/atvbaha.112.300741

Cited by 292 publications

(307 citation statements)

References 36 publications

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“…In general, cellular miRNAs can passively leak from damaged cells or can be actively secreted into the extracellular space or circulation via the microvesicle pathway (34,35) or within HDL protein complexes (36,37). The expressions and functions of miR-196a, miR-30a, and miR-490 miRNAs in their respective tissues also support a role for these miRNAs as potential biomarkers of FSGS disease activity.…”

Section: Discussionmentioning

confidence: 97%

Evaluation of MicroRNAs miR-196a, miR-30a-5P, and miR-490 as Biomarkers of Disease Activity among Patients with FSGS

Zhang

Chen

et al. 2014

Clinical Journal of the American Society of Nephrology

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Background and objectives This study aimed to identify urinary microRNAs (miRNAs) as biomarkers for FSGS disease activity.Design, setting, participants, & measurements Candidate urinary miRNAs were identified in pooled urine samples from patients with active FSGS (FSGS-A) and FSGS in remission (FSGS-CR), and were then validated using individual samples. Their levels were compared both under different treatment responses in a prospective study of FSGS and in patients with different membranous nephropathy (MN) and diabetic nephropathy (DN) disease activity. The prediction of these miRNAs for treatment responses was further analyzed in both retrospective and prospective cohorts of patients with FSGS.Results All 54 miRNAs were included as candidate biomarkers, including those with high levels in patients with FSGS-A (n=9) under the TaqMan Low Density Array as well as those with conserved expression in kidneys and involved in immune response. TaqMan probe-based quantitative RT-PCR confirmed the higher levels of four miRNAs in patients with FSGS-A in two independent cohorts (n=18 and n=80). Urinary miR-196a, miR-30a-5p, and miR-490 discriminated FSGS-A from FSGS-CR, with an area under the curve of $0.80. After steroid treatment, their levels were lower in steroid-responsive patients with FSGS (all P,0.001), but were unchanged in steroid-resistant patients. The levels of miRNAs were similar between active MN and MN in remission as well as active DN and incipient DN (all P.0.05). Urinary miR-30a-5p marginally predicted the response to steroid treatment in patients with FSGS-A, with an area under the curve of 0.63 (P=0.03). ConclusionsThe levels of urinary miR-196a, miR-30a-5p, and miR-490 are associated with FSGS disease activity.

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Section: Discussionmentioning

confidence: 97%

Evaluation of MicroRNAs miR-196a, miR-30a-5P, and miR-490 as Biomarkers of Disease Activity among Patients with FSGS

Zhang

Chen

et al. 2014

Clinical Journal of the American Society of Nephrology

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“…Newer studies recommend exploring not just the circulating miRNAs, but also their carriers (80). Circulating miRNAs are present in blood in three different forms: associated with Argonaute complexes (81), connected to lipoproteins (82) and encapsulated in extracellular vesicles (EVs) (83). The most appealing form of blood circulating miRNAs, are those associated with EVs.…”

Section: Future Perspectives Future Perspectivesmentioning

confidence: 99%

Patients After Splenectomy: Old Risks and New Perspectives

Dragomir¹,

Petrescu²,

Manga³

et al. 2016

chr

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Rezumat Pacienåii post-splenectomie: complicaåii cunoscute aei perspective noiComplicaåiile care survin în urma splenectomiei pot fi împãråite în infecåioase aei non-infecåioase. Legãtura dintre splenectomie aei aceste riscuri este doar paråial înåeleasã. Rãspunsul imun al gazdei împotriva infecåiei este profund modificat post-splenectomie, iar aceaeti indivizi sunt mai susceptibili sã dezvolte sepsis aei infecåia are o evoluåie fulminantã. Splenectomia este de asemenea un potenåial factor de risc pentru numeroase complicaåii vasculare care rezultã în urma obstrucåiei paråiale sau totale ale unei artere sau vene. În plus, hipertensiunea pulmonarã poate fi o complicaåie severã aei uneori fatalã a splenectomiei. Unii autori includ aei neoplaziile, diabetul zaharat aei pancreatita acutã în categoria complicaåiilor non-infecåioase post-splenectomie. Cea mai de temut complicaåie pentru pacienåii splenectomizaåi rãmâne sepsisul. Fiziopatologia sepsisului încã este controversatã. Decesul în sepsis poate surveni fie în urma hiperinflamaåiei, fie în urma imunosupresiei. Multiple dovezi experimentale au dovedit implicarea microRNA-urilor celulare aei virale în sepsis. Considerãm faptul cã microRNA-urile sunt de asemenea asociate cu imunosupresia pacientului asplenic, ceea ce determinã o creaetere a riscului de sepsis fatal. Studierea nivelului expresiei plasmatice a microRNA-urilor circulante la pacienåii asplenici, ar putea conduce la o mai bunã înåelegere a imunosupresiei post-splenectomie aei la dezvoltarea unor noi metode diagnostice aei terapeutice.Cuvinte cheie: splenectomie, microRNA, sepsis, microRNA-uri virale, OPSI AbstractThe risks that arise after splenectomy can be divided in infectious and non-infectious. The link between splenectomy and these hazards remains partially unknown. Host defense against infection is altered after splenectomy and such individuals develop sepsis more easily and the infection has a fulminant course. Splenectomy is also a potential risk factor for several vascular complications that result from partial or total obstruction of an arterial or venous blood vessel. Furthermore, pulmonary hypertensioncan be a severe and sometimes fatal complication following splenectomy. Some authors also consider that malignancies, diabetes mellitus and acute pancreatitis are non-infectious complications after splenectomy. The most feared complication for splenectomized patients remains sepsis. The pathophysiology of sepsis is still controversial. Death in sepsis can occur due to either hyper-inflammation or "immune paralysis". Multiple experimental evidences link cellular and viral microRNAs with sepsis. We presume that General ReportChirurgia (2016)

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“…miRNAs are resistant to nucleases due to their small size and the fact that in body fluids, they are likely protected in extracellular evesicles (EVs) or bound to protein or high‐density lipoprotein (HDL) binding partners (Brase, Wuttig, Kuner & Sultmann, 2010; Cortez et al., 2012; Reid, Kirschner & van Zandwijk, 2011; Wagner et al., 2013). This reservoir of miRNAs may transit to other cells and tissues where in some cases they influence gene regulation and may play a role in physiology and pathology (Hergenreider et al., 2012; Wei et al., 2017; Zhang et al., 2010, 2015).…”

Section: Introductionmentioning

confidence: 99%

Extracellular RNA profiles with human age

Dluzen

Hooten

et al. 2018

Aging Cell

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SummaryCirculating extracellular RNAs (exRNAs) are potential biomarkers of disease. We thus hypothesized that age‐related changes in exRNAs can identify age‐related processes. We profiled both large and small RNAs in human serum to investigate changes associated with normal aging. exRNA was sequenced in 13 young (30–32 years) and 10 old (80–85 years) African American women to identify all RNA transcripts present in serum. We identified age‐related differences in several RNA biotypes, including mitochondrial transfer RNAs, mitochondrial ribosomal RNA, and unprocessed pseudogenes. Age‐related differences in unique RNA transcripts were further validated in an expanded cohort. Pathway analysis revealed that EIF2 signaling, oxidative phosphorylation, and mitochondrial dysfunction were among the top pathways shared between young and old. Protein interaction networks revealed distinct clusters of functionally‐related protein‐coding genes in both age groups. These data provide timely and relevant insight into the exRNA repertoire in serum and its change with aging.

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Characterization of Levels and Cellular Transfer of Circulating Lipoprotein-Bound MicroRNAs

Cited by 292 publications

References 36 publications

Evaluation of MicroRNAs miR-196a, miR-30a-5P, and miR-490 as Biomarkers of Disease Activity among Patients with FSGS

Evaluation of MicroRNAs miR-196a, miR-30a-5P, and miR-490 as Biomarkers of Disease Activity among Patients with FSGS

Patients After Splenectomy: Old Risks and New Perspectives

Extracellular RNA profiles with human age

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