DOI: 10.5281/zenodo.4630944
title: 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

description: <strong>Dataset related to the article with title: MicroRNA-21/</strong><strong>PDCD4</strong> <strong>proapoptotic signaling from circulating CD34<sup>+</sup> cells to vascular endothelial cells: a potential contributor to adverse cardiovascular outcomes in patients with critical limb ischemia </strong> By:Gaia Spinetti<sup>1</sup>, Elena Sangalli<sup>1</sup>, Elena Tagliabue<sup>1</sup>, Davide Maselli<sup>1</sup>, Ornella Colpani<sup>1</sup>, David Ferland-McCollough<sup>2</sup>, Franco Carnelli<sup>1</sup>, Patrizia Orlando<sup>1</sup>, Agostino Paccagnella<sup>3</sup>, Anna Furlan<sup>3</sup>, Piero Maria Stefani<sup>3</sup>, Luisa Sambado<sup>3</sup>, Maria Sambataro<sup>3</sup>, and Paolo Madeddu<sup>2</sup>. <sup>1</sup>IRCCS MultiMedica, Milan, Italy;<sup> 2</sup>University of Bristol, Bristol, UK, <sup>3</sup>Ca Foncello Hospital, Treviso, Italy. Diabetes Care. 2020 Jul;43(7):1520-1529. doi: 10.2337/dc19-2227. Epub 2020 May 1. <strong>Abstract</strong> <strong>Objective</strong>. In patients with type 2 diabetes (T2D) and critical limb ischemia (CLI), migration of circulating CD34<sup>+</sup> cells predicted cardiovascular mortality at 18 months post-revascularization. This study aimed to provide long-term validation and mechanistic understanding of the biomarker. <strong>Research Design and Methods</strong>. The association between CD34<sup>+</sup> 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<sup>+</sup> 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<sup>+</sup> cells to endothelial cells. <strong>Results</strong>. Multivariable regression analysis confirmed CD34<sup>+</sup> cell migration forecasts long-term cardiovascular mortality. CD34<sup>+</sup> 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<sup>+</sup> cells phenocopied the T2D-CLI cell behavior. In coculture, T2D-CLI CD34<sup>+</sup> 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<sup>+</sup> cells <strong>Conclusions</strong>. Migration of CD34<sup>+</sup> cells predicts long-term cardiovascular mortality in T2D-CLI patients. An altered paracrine signalling conveys anti-angiogenic and pro-apoptotic features from CD34<sup>+</sup> cells to the endothelium. This damaging interaction may increase the risk for life-threatening complications.