Dataset related to the article: microRNA-21/PDCD4 Proapoptotic Signaling From Circulating CD34+ Cells to Vascular Endothelial Cells: A Potential Contributor to Adverse Cardiovascular Outcomes in Patients With Critical Limb Ischemia

  • Gaia Spinetti (Creator)
  • Elena Sangalli (Creator)
  • Elena Tagliabue (Creator)
  • Davide Maselli (Creator)
  • Ornella Colpani (Creator)
  • David Ferland-McCollough (Istituti di Ricovero e Cura a Carattere Scientifico) (Creator)
  • Franco Carnelli (Creator)
  • Patrizia Orlando (Creator)
  • Agostino Paccagnella (Creator)
  • Anna Furlan (Creator)
  • Piero Maria Stefani (Creator)
  • Luisa Sambado (Creator)
  • Maria Sambataro (Creator)
  • Paolo R Madeddu (Creator)



Dataset related to the article with title: MicroRNA-21/PDCD4 proapoptotic signaling from circulating CD34+ cells to vascular endothelial cells: a potential contributor to adverse cardiovascular outcomes in patients with critical limb ischemia By:Gaia Spinetti1, Elena Sangalli1, Elena Tagliabue1, Davide Maselli1, Ornella Colpani1, David Ferland-McCollough2, Franco Carnelli1, Patrizia Orlando1, Agostino Paccagnella3, Anna Furlan3, Piero Maria Stefani3, Luisa Sambado3, Maria Sambataro3, and Paolo Madeddu2. 1IRCCS MultiMedica, Milan, Italy; 2University of Bristol, Bristol, UK, 3Ca Foncello Hospital, Treviso, Italy. Diabetes Care. 2020 Jul;43(7):1520-1529. doi: 10.2337/dc19-2227. Epub 2020 May 1. Abstract Objective. In patients with type 2 diabetes (T2D) and critical limb ischemia (CLI), migration of circulating CD34+ cells predicted cardiovascular mortality at 18 months post-revascularization. This study aimed to provide long-term validation and mechanistic understanding of the biomarker. Research Design and Methods. The association between CD34+ cell migration and cardiovascular mortality was reassessed at 6 years post-revascularization. In a new series of T2D-CLI and control subjects, immuno-sorted bone marrow (BM)-CD34+ cells were profiled for microRNA expression and assessed for apoptosis and angiogenesis activity. The differentially regulated microRNA-21, and its pro-apoptotic target PDCD4, were titrated to verify their contribution in transferring damaging signals from CD34+ cells to endothelial cells. Results. Multivariable regression analysis confirmed CD34+ cell migration forecasts long-term cardiovascular mortality. CD34+ cells from T2D-CLI patients were more apoptotic and less proangiogenic than controls and featured microRNA-21 downregulation, modulation of several long non-coding RNAs acting as microRNA-21 sponges, and upregulation of the microRNA-21 proapoptotic target PDCD4. Silencing miR-21 in control CD34+ cells phenocopied the T2D-CLI cell behavior. In coculture, T2D-CLI CD34+ cells imprinted naïve endothelial cells, increasing apoptosis, reducing network formation, and modulating the TUG1 sponge/microRNA-21/PDCD4 axis. Silencing PDCD4 or scavenging ROS protected endothelial cells from the negative influence of T2D-CLI CD34+ cells Conclusions. Migration of CD34+ cells predicts long-term cardiovascular mortality in T2D-CLI patients. An altered paracrine signalling conveys anti-angiogenic and pro-apoptotic features from CD34+ cells to the endothelium. This damaging interaction may increase the risk for life-threatening complications.
Date made available23 Mar 2021

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