Blood-Derived Extracellular RNA and Platelet Pathobiology

Clancy, Lauren; Freedman, Jane E.

doi:10.1161/circresaha.115.308190

Cited by 8 publications

(7 citation statements)

References 15 publications

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“…Future perspectives point toward an important role for miRNA in platelet function and therapy [ 110 ]. Indeed, recent studies revealed important roles for miRNA in platelet development, function and CVD [ 111 ].…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Platelets, diabetes and myocardial ischemia/reperfusion injury

Russo

Penna

Musso

et al. 2017

Cardiovasc Diabetol

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Mechanisms underlying the pathogenesis of ischemia/reperfusion injury are particularly complex, multifactorial and highly interconnected. A complex and entangled interaction is also emerging between platelet function, antiplatelet drugs, coronary diseases and ischemia/reperfusion injury, especially in diabetic conditions. Here we briefly summarize features of antiplatelet therapy in type 2 diabetes (T2DM). We also treat the influence of T2DM on ischemia/reperfusion injury and how anti-platelet therapies affect post-ischemic myocardial damage through pleiotropic properties not related to their anti-aggregating effects. miRNA-based signature associated with T2DM and its cardiovascular disease complications are also briefly considered. Influence of anti-platelet therapies and different effects of healthy and diabetic platelets on ischemia/reperfusion injury need to be further clarified in order to enhance patient benefits from antiplatelet therapy and revascularization. Here we provide insight on the difficulty to reduce the cardiovascular risk in diabetic patients and report novel information on the cardioprotective role of widely used anti-aggregant drugs.

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Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Platelets, diabetes and myocardial ischemia/reperfusion injury

Russo

Penna

Musso

et al. 2017

Cardiovasc Diabetol

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“…Most platelet RNA expression results from the transcription of nuclear DNA in the megakaryocyte 22 , 25 , and thus reflects the status of the megakaryocyte at the time of platelet release into the circulation, as well as subsequent splicing events, selective packaging, and intercellular RNA transfer. There is emerging evidence 26 , 27 , 28 , 29 , 30 that the molecular signature of platelets may be changed in disease conditions where these processes are altered, including via inter-cellular transfer 27 , 29 of cytosolic RNA. In the context of MPNs, the platelet transcriptome therefore not only represents a critical biomarker of megakaryocytic activity 31 , 32 , 33 , 34 , 35 , but also provides a snapshot of the underlying hemostatic, thrombotic, and inflammatory derangements associated with these hematologic neoplasms and the potential impact of treatment 34 .…”

Section: Introductionmentioning

confidence: 99%

Platelet transcriptome identifies progressive markers and potential therapeutic targets in chronic myeloproliferative neoplasms

Shen¹,

Du²,

Perkins³

et al. 2021

Cell Reports Medicine

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Predicting disease progression remains a particularly challenging endeavor in chronic degenerative disorders and cancer, thus limiting early detection, risk stratification, and preventive interventions. Here, profiling the three chronic subtypes of myeloproliferative neoplasms (MPNs), we identify the blood platelet transcriptome as a proxy strategy for highly sensitive progression biomarkers that also enables prediction of advanced disease via machine-learning algorithms. The MPN platelet transcriptome reveals an incremental molecular reprogramming that is independent of patient driver mutation status or therapy. Subtype-specific markers offer mechanistic and therapeutic insights, and highlight impaired proteostasis and a persistent integrated stress response. Using a LASSO model with validation in two independent cohorts, we identify the advanced subtype MF at high accuracy and offer a robust progression signature toward clinical translation. Our platelet transcriptome snapshot of chronic MPNs demonstrates a proof-of-principle for disease risk stratification and progression beyond genetic data alone, with potential utility in other progressive disorders.

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“…In addition to a substantial protein cargo, they contain a wealth of RNA: messenger RNAs (mRNAs), unspliced pre-mRNAs, rRNAs, and tRNAs. 5 The platelet transcriptome is modified during circulation, due to altered splicing 6 or uptake of mRNAs transferred from other cells, 7 , 8 and specific platelet transcriptome signatures have been reported in cardiovascular diseases and solid tumors. 9 Examination of the platelet transcriptome in MPNs should therefore be very revealing, as it reflects the transcriptional state of parent megakaryocytes at the time of platelet release, as well as stimuli encountered during peripheral circulation ( Figure 1 ).…”

Section: Main Textmentioning

confidence: 99%