miR-130a and Tgfβ Content in Extracellular Vesicles Derived from the Serum of Subjects at High Cardiovascular Risk Predicts their In-Vivo Angiogenic Potential

• Published in: Scientific reports Vol. 10; no. 1; p. 706
• Main Authors: Cavallari, Claudia, Figliolini, Federico, Tapparo, Marta, Cedrino, Massimo, Trevisan, Alessandra, Positello, Lorenza, Rispoli, Pietro, Solini, Anna, Migliaretti, Giuseppe, Camussi, Giovanni, Brizzi, Maria Felice
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 20.01.2020; Nature Publishing Group
• Subjects: 13; 3' Untranslated Regions; 38; 38/61; 38/77; 38/90; 631/154/53/2423; 64/60; 692/699/317; 82; Adult; Aged; Angiogenesis; Cardiovascular diseases; Cardiovascular Diseases - blood; Cardiovascular Diseases - genetics; Cardiovascular Diseases - metabolism; Case-Control Studies; Diabetes; Diabetes mellitus; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - metabolism; Extracellular vesicles; Extracellular Vesicles - genetics; Extracellular Vesicles - metabolism; Female; Health care; Health risks; Homeodomain Proteins - genetics; Humanities and Social Sciences; Humans; Ischemia; Male; MicroRNAs; MicroRNAs - genetics; Middle Aged; multidisciplinary; Patients; Science; Science (multidisciplinary); Transforming Growth Factor beta - metabolism
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-55783-7

Serum-derived extracellular vesicles (sEV) from healthy donors display in-vivo pro-angiogenic properties. To identify patients that may benefit from autologous sEV administration for pro-angiogenic purposes, sEV angiogenic capability has been evaluated in type 2 diabetic (T2DM) subjects (D), in obese individuals with (OD) and without (O) T2DM, and in subjects with ischemic disease (IC) (9 patients/group). sEV display different angiogenic properties in such cluster of individuals. miRNomic profile and TGFβ content in sEV were evaluated. We found that miR-130a and TGFβ content correlates with sEV in-vitro and in-vivo angiogenic properties, particularly in T2DM patients. Ingenuity Pathway Analysis (IPA) identified a number of genes as among the most significant miR-130a interactors. Gain-of-function experiments recognized homeoboxA5 (HOXA5) as a miR-130a specific target. Finally, ROC curve analyses revealed that sEV ineffectiveness could be predicted (Likelihood Ratio+ (LH+) = 3.3 IC 95% from 2.6 to 3.9) by comparing miR-130a and TGFβ content ‘in Series’. We demonstrate that sEV from high cardiovascular risk patients have different angiogenic properties and that miR-130a and TGFβ sEV content predicts ‘true ineffective sEVs’. These results provide the rationale for the use of these assays to identify patients that may benefit from autologous sEV administration to boost the angiogenetic process.