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Engineering living, multilayered blood vessels to form in vivo arteries is a promising alternative to peripheral artery bypass using acellular grafts restricted by thrombosis and occlusion at long term. Bone Morphogenetic Protein 2 (BMP2) is a growth factor determining in the early vascular embryonic development. The aim of the present study was evaluate the collaborative effect of recombinant human-BMP2 and Bone marrow-Mesenchymal stem cells (BM-MSCs) seeded on vascular patch to regenerate a vascular arterial wall in a rat model. BM-MSCs expressing green fluorescent protein (GFP) seeded on vascular patch were cultured in presence of recombinant human-BMP2 [100 ng/mL] during 1 week before their implantation on the abdominal aorta of Wistar rats. We observed after 2 weeks under physiological arterial flow a regeneration of a three layers adult-like arterial wall with a middle layer expressing smooth muscle proteins and a border layer expressing endothelial marker. In vitro study, using Matrigel assay and co-culture of BM-MSCs with endothelial cells demonstrated that rh-BMP2 promoted tube-like formation even at long term (90 days) allowing the organization of thick rails. We demonstrated using inhibitors and siRNAs that rh-BMP2 enhanced the expression of HIF-1α and Id1 through, at least in part, the stimulation of JAK2/STAT3/STAT5 signaling pathways. Rh-BMP2 by mimicking embryological conditions allowed vascular BM-MSCs differentiation. [ABSTRACT FROM AUTHOR]

Objective: Percutaneous branch Pulmonary Artery (PA) stenting can be challenging, especially when associated with stenosis of the Right Ventricular Outflow Tract (RVOT), after previous angioplasty or with complexity of PAs branches. Surgical patch enlargement of Pas alone can be disappointing in these situations. A hybrid-approach, with PA stenting during surgery, may be an alternative to optimize surgical management in complex pulmonary artery stenosis. Methods: In a 2 year period, 14 consecutive patients with PA stenosis associated with congenital heart disease underwent intraoperative PA stenting. We retrospectively analyzed clinical data, procedural details and outcomes of all patients. Results: 14 patients (1 female), underwent hybrid stenting of the PA. The median age was 6.9 years (range 6 days to 28 years). Primary cardiac diagnoses were pulmonary atresia ( n = 7), tetralogy of Fallot ( n = 5) and other ( n = 2). The left PA was stented in 4 patients, the right in 1 patient and both in 8 patients, for a total of 21 stents. The median maximal balloon diameter was 12 mm (range 6 to 25 mm). Concomitant surgical procedures were RVOT reconstruction with PA patch angioplasty ( n = 8), pulmonary valve replacement ( n = 3) and other ( n = 3). Active suture fixation of the proximal stent was performed in each case. No complications occurred during stent implantation, and no significant cardiac complications occurred perioperatively. The median length of stay in the intensive care unit was 2 days (range 2 to 7 days). The mean follow-up was 9.8 months (range 1 to 19 months). Echocardiography at discharge showed good results in PA branches: the mean peak gradient was 3.8 mmHg (range 0 to 14 mmHg). Most patients showed significant fall in right ventricular systolic pressure after the procedure. No stent needed repeat dilatation. Conclusion: Hybrid PA stenting during surgery for congenital heart disease in cases of complex branch PA stenosis is an alternative to traditional angioplasty. The procedure is safe and effective, and ameliorates right-ventricular dysfunction. [ABSTRACT FROM AUTHOR]

Sterile inflammation is a key determinant of myocardial reperfusion injuries. It participates in infarct size determination in acute myocardial infarction and graft rejection following heart transplantation. We previously showed that P2Y11 exerted an immunosuppressive role in human dendritic cells, modulated cardiofibroblasts' response to ischemia/reperfusion in vitro and delayed graft rejection in an allogeneic heterotopic heart transplantation model. We sought to investigate a possible role of P2Y11 in the cellular response of cardiomyocytes to ischemia/reperfusion. We subjected human AC16 cardiomyocytes to 5 h hypoxia/1 h reoxygenation (H/R). P2Y11R (P2Y11 receptor) selective agonist NF546 and/or antagonist NF340 were added at the onset of reoxygenation. Cellular damages were assessed by LDH release, MTT assay and intracellular ATP level; intracellular signaling pathways were explored. The role of P2Y11R in mitochondria-derived ROS production and mitochondrial respiration was investigated. In vitro H/R injuries were significantly reduced by P2Y11R stimulation at reoxygenation. This protection was suppressed with P2Y11R antagonism. P2Y11R stimulation following H2O2-induced oxidative stress reduced mitochondria-derived ROS production and damages through PKCε signaling pathway activation. Our results suggest a novel protective role of P2Y11 in cardiomyocytes against reperfusion injuries. Pharmacological post-conditioning targeting P2Y11R could therefore contribute to improve myocardial ischemia/reperfusion outcomes in acute myocardial infarction and cardiac transplantation. [ABSTRACT FROM AUTHOR]