Distinct Platelet Ribonucleic Acid Signatures in Patients with Pulmonary Hypertension.
Rationale: Pulmonary hypertension encompasses progressive disorders leading to right ventricular dysfunction and early death. Late detection is an important cause of poor clinical outcomes. However, biomarkers that accurately predict the presence of pulmonary hypertension are currently lacking. Obje...
| Publicado en: | Annals of the American Thoracic Society Vol. 19; no. 10; pp. 1650 - 1661 |
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| Autores principales: | , , , , , , , , , , , , , , , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Oxford University Press / USA
Oct2022
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=159485145&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 159485145 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 23296933 FUCV jtl: Annals of the American Thoracic Society issn: 23296933 maglogo: N pubinfo: dt: Oct2022 vid: 19 iid: 10 pid: 622 pub: Oxford University Press / USA artinfo: ui: 159485145 159485145 NLM35537078 159485145 10.1513/AnnalsATS.202201-085OC NLM35537078 159485145 ppf: 1650 ppct: 11 formats: tig: atl: Distinct Platelet Ribonucleic Acid Signatures in Patients with Pulmonary Hypertension. aug: au: Smits, A. Josien Arkani, Mohammad In 't Veld, Sjors G. J. G. Huis in 't Veld, Anna E. Sol, Nik Groeneveldt, Joanne A. Botros, Liza Braams, Natalia J. Jansen, Samara M. A. Ramaker, Jip Zwaan, Kenn Post, Edward Nossent, Esther J. Boonstra, Anco de Man, Frances S. Noordegraaf, Anton Vonk Gomez-Arroyo, Jose Best, Myron G. Wurdinger, Tom Bogaard, Harm Jan affil: Department of PulmonaryMedicine, Amsterdam Cardiovascular Sciences, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands sug: subj: Blood Platelets Hypertension, Pulmonary Hypertension, Pulmonary Diagnosis RNA Anticoagulants Human ab: Rationale: Pulmonary hypertension encompasses progressive disorders leading to right ventricular dysfunction and early death. Late detection is an important cause of poor clinical outcomes. However, biomarkers that accurately predict the presence of pulmonary hypertension are currently lacking. Objectives: In this study, we provide evidence that blood platelets contain a distinctive ribonucleic acid (RNA) profile that may be exploited for the detection of pulmonary hypertension. Methods: Blood platelet RNA was isolated prospectively from 177 prevalent patients with different subtypes of pulmonary hypertension as well as 195 control subjects clinically not suspected of pulmonary hypertension. Sequencing libraries were created using SMARTer (Switching Mechanism at 5' end of RNA Template) copy desoxyribonucleic acid amplification and sequenced on the Illumina High Throughput Sequencing platform. RNA-sequencing reads were mapped to the human reference genome, and intron-spanning spliced RNA reads were selected. Differential spliced RNA panels were calculated by analysis of variance statistics. A particle swarm optimization-enhanced classification algorithm was built employing a development (n = 213 samples) and independent validation series (n = 159 samples). Results: We detected a total of 4,014 different RNAs in blood platelets from patients with pulmonary hypertension (n = 177) and asymptomatic control subjects (n = 195). Gene ontology analysis revealed enhanced RNA concentrations for genes related to RNA processing, translation, and mitochondrial function. A particle swarm optimization-selected RNA panel of 408 distinctive differentially spliced RNAs mediated detection of pulmonary hypertension with 93% sensitivity, 62% specificity, 77% accuracy, 0.89 (95% confidence interval, 0.83-0.93) area under the curve, and a negative predictive value of 91% in the independent validation series. The prediction score was independent of age, sex, smoking, pulmonary hypertension subtype, and the use of pulmonary hypertension-specific medication or anticoagulants. Conclusions: A platelet RNA panel may accurately discriminate patients with pulmonary hypertension from asymptomatic control subjects. In the light of current diagnostic delays, this study is the starting point for further development and evaluation of a platelet RNA-based blood test to ultimately improve early diagnosis and clinical outcomes in patients with pulmonary hypertension. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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