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

被引:19
作者
Cavallari, Claudia [1 ]
Figliolini, Federico [1 ]
Tapparo, Marta [2 ]
Cedrino, Massimo [2 ]
Trevisan, Alessandra [3 ]
Positello, Lorenza [2 ]
Rispoli, Pietro [3 ]
Solini, Anna [4 ]
Migliaretti, Giuseppe [5 ]
Camussi, Giovanni [1 ,2 ]
Brizzi, Maria Felice [1 ,2 ]
机构
[1] Univ Turin, 2I3T Scarl, Turin, Italy
[2] Univ Turin, Dept Med Sci, Turin, Italy
[3] Univ Turin, Dept Surg Sci, Turin, Italy
[4] Univ Pisa, Dept Surg Med Mol & Crit Area Pathol, Pisa, Italy
[5] Univ Turin, Dept Publ Hlth & Pediat Sci, Turin, Italy
关键词
ENDOTHELIAL-CELLS; TUMOR-DEVELOPMENT; MICROPARTICLES; MICROVESICLES; EXOSOMES; OBESITY; BIOMARKERS; MICRORNAS; APOPTOSIS; DISEASE;
D O I
10.1038/s41598-019-55783-7
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
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 TGF beta content in sEV were evaluated. We found that miR-130a and TGF beta 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 TGF beta content 'in Series'. We demonstrate that sEV from high cardiovascular risk patients have different angiogenic properties and that miR-130a and TGF beta 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.
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页数:13
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