Plasma exosomes after PCI in non-diabetic STEMI patients fed barley beta-D-glucan-enriched pasta reduce oxidative stress-induced endothelial cell senescence.

Background: Endothelial aging delays endothelialization, which increases restenosis risk in acute coronary syndrome with ST segment elevation (STEMI) patients following primary percutaneous coronary intervention (PCI). Normocaloric diet supplemented with barley beta-D-glucan (BBG)-enriched pasta protects the heart, although its significance in releasing exosomes that prevent endothelium aging after PCI is unknown. Methods: In non-diabetic anterior STEMI patients (mean age 57 years, 8 women) who undeerwent PCI, we isolated plasma exosomes (pEXOs) before (T0) and after 3 months (T1) of normocaloric diet supplemented with 100g of pasta containing 3g of BBG (STEMI-BBG, n=19) or without supplementation (STEMI-C, n=18). Nanoparticle tracking analysis (NTA) detected pEXOs size and levels. Senescent human umbilical vein endothelial cells (HUVECs) induced by H2O2 (100 μmol/l for 24 h) were detected by assessing senescence- associated β-galactosidase activity. HUVECs were treated with pEXOs (107particles/ml) for 24h without and with H2O2. Dihydroethidium staining detected oxygen free radicals (ROS) in HUVECs. Results: pEXOs levels were significantly increased at T1 in STEMI-BBG group, but not in STEMI-C patients. The NTA revealed that large pEXOs contribute to this increase, but not the other exosomal subpopulations. T0 and T1 pEXOs isolated from all patients induced premature endothelial senescence in the absence of ROS increase. Otherwise, T1 pEXOs isolated from STEMI-BBG patients significantly prevented worsening of endothelial senescence induced by exogenous H2O2 via reducing oxidative stress (p<0.05), but not T1 pEXOs from STEMI-C. Conclusion: Our findings indicate that pEXOs obtained from reperfused non-diabetic STEMI patients spread pro-senescent signals into HUVECs. However, the presence of pEXOs isolated from reperfused STEMI patients fed BBG-enriched pasta did not exacerbate the endothelial senescence induced by H2O2. We can hypothesize that these effects could be related to different transcriptional landscape related to microenvironment.