MiRNA-30d and miR-770-5p as potential clinical risk predictors of Vasoplegic Syndrome in Patients undergoing on-pump coronary artery bypass grafting.

The aims of this study were to perform pre-surgery miRNA profiling of patients who develop Vasoplegic syndrome (VS) after coronary artery bypass grafting (CABG) and identify those miRNAs that could be used as VS prognostic tools and biomarkers. The levels of 754 microRNAs (miRNAs) were measured in whole blood samples from a cohort of patients collected right before the coronary artery bypass grafting (CABG) surgery. We compared the miRNA levels of those who developed VS (VASO group) with those who did not (NONVASO group) after surgery. Six miRNAs (hsa-miR-548c-3p, -199b-5p, -383-5p -571 -183-3p, -30d-5p) were increased and two (hsa-1236-3p, and hsa-miR770-5p) were decreased in blood of VASO compared to NONVASO groups. Receiver Operating Characteristic (ROC) curve analysis revealed that a combination of the miRNAs, hsa-miR-30d-5p and hsa-miR-770-5p can be used as VS predictors (AUC = 0.9615, p < 0.0001). The computational and functional analyses were performed to gain insights into the potential role of these dysregulated miRNAs in VS and have identified the "Apelin Liver Signaling Pathway" as the canonical pathway containing the most target genes regulated by these miRNAs. The expression of the combined miRNAs hsa-miR-30d and hsa-miR-770-5p allowed the ability to distinguish between patients who could and could not develop VS, representing a potential predictive biomarker of VS.

Lipid core nanoparticles as vehicle for docetaxel reduces atherosclerotic lesion, inflammation, cell death and proliferation in an atherosclerosis rabbit model.

Chemotherapeutic agents used in cancer treatment associated to nanoparticles (LDE) that mimic the composition of low-density lipoprotein and buffer their toxicity can have strong anti-atherosclerosis action, as we showed in cholesterol-fed rabbits. Here, a novel preparation of docetaxel (DTX) carried in LDE was evaluated. Eighteen rabbits were fed 1% cholesterol during 8 weeks. After the first 4 weeks, 9 animals were treated for 4 weeks with intravenous LDE-DTX (1 mg/kg/week) and 9 with LDE only (controls) once a week for 4 weeks. Animals were then euthanized and the aortas were analyzed for morphometry, immunohistochemistry and Western blot. LDE-DTX treated group showed 80% reduction of atheroma area compared to controls. LDE-DTX treatment reduced in 60% the protein expression of macrophage marker CD68 and of MCP-1 in 80%. LDE-DTX pronouncedly lowered expression of pro-inflammatory markers NF-κB, TNF-α, IL-1ß, IL-6 and von Willebrand factor and elicited 40% reduction in cell proliferation marker PCNA. The presence of smooth muscle cells in the intima was 85% smaller than in controls. Pro-apoptotic caspase 3, caspase 9, Bax, and anti-apoptotic Bcl-2 all were reduced by LDE-DTX. Protein expression of MMP-2 and MMP-9, TGF-ß, and collagen 1 and 3 were also markedly lowered by the LDE-DTX treatment. Animals showed no hematological, hepatic or renal toxicity consequent to LDE-DTX treatment. In conclusion, LDE-DTX showed a wide array of strong effects on pro-inflammatory and proliferation-promoting factors that drive the lesion development. These findings and the lack of observable toxicity indicate that LDE-DTX can be a candidate for future clinical trials.