Autologous vein grafts is still commonly used for arterial reconstructive procedures. Their success is limited by the development of neointimal hyperplasia. Clinical and experimental evidence suggest that the bone marrow derived mesenchymal stem cells (MSCs) participate in the neovascularization. The current study used a direct approach to test the hypothesis that, after vein grafting in a rat model, MSCs have potential effects on reendothelialization and neointimal formation. MSCs were isolated by bone marrow cell adherence. Autologously interpositioning left external jugular vein (LEJV) to left common carotid artery-induced vein grafting model of r at w as utilized. Vascular lesion formation after transplantation of MSCs labeled with 4',6-diamidino-2-phenylindole (DAPI) was investigated. Two weeks after implantation, immunofluorescence studies revealed that engrafted cells acquired an endothelial phenotype, and some expressed endothelial nitric oxide synthase (eNOS). Furthermore, proliferation of cells and neointimal formation decreased significantly after MSC implantation. Real-time reverse transcription-PCR and western blotting analysis showed a rise of eNOS expression in the MSC group compared with the vein grafting group. Therefore, engrafted MSCs appeared to differentiate into endothelial cells, diminish the neointima formation and contribute to the improvement on endothelial function, which indicates that MSCs may exert an important function as repair mechanism in vascular injury after vein grafting.
To date, hypoxia-inducible factor 1a (HIF-1a) and astrocyte elevated gene-1 (AEG-1) have been involved in the proliferation, migration and morphological changes of vascular smooth muscle cells. However, the potential relationship of HIF-1a-AEG-1 pathway in human aortic smooth muscle cell (HASMC) has not been reported. In the present study, in-vitro assays were utilized to explore the potential impact of HIF-1a-AEG-1 signaling on HASMC phenotype. Here, we found that HIF-1a expression was up-regulated in the media of thoracic aortic dissection tissues as compared with normal aortic tissues, and was associated with increased apoptotic SMCs and decreased AEG-1 expression. Mechanically, hypoxia promoted the expression of HIF-1a by PI3K-AKT pathway in HASMCs; HIF-1a further suppressed the expressions of AEG-1, a-SMA and SM22a, and promoted osteopontin (OPN) expression. Functionally, HIF-1a inhibited the proliferation and migration of HASMCs. However, si-HIF-1a or Akt inhibitor abrogated HIF-1a-mediated related expressions and biological effects above. In conclusion, HIF-1a induces HASMC phenotype switch, and closely related to PI3K/AKT and AEG-1 signaling, which may provide new avenues for the prevention and treatment of aortic dissection diseases.
Bone marrow‐derived mesenchymal stem cells (BMSCs) have great therapeutic potential for many diseases. However, the homing of BMSCs to injury sites remains a difficult problem. Recent evidence indicates that simvastatin stimulates AKT phosphorylation, and p‐AKT affects the expression of chemokine (CXC motif) receptor‐4 (CXCR4). Therefore, simvastatin may improve the expression of CXCR4 in BMSCs, and microRNAs (miRs) may participate in this process. In this study, we demonstrated that simvastatin increased both the total and the surface expression of CXCR4 in BMSCs. Stromal cell‐derived factor‐1α (SDF‑1α)‐induced migration of BMSCs was also enhanced by simvastatin, and this action was inhibited by AMD 3100(a chemokine receptor antagonist for CXCR4). The PI3K/AKT pathway was activated by simvastatin in this process, and LY294002 reversed the overexpression of CXCR4 caused by simvastatin. MiR‐9 directly targeted CXCR4 in rat BMSCs, and simvastatin decreased miR‐9 expression. P‐AKT affected the expression of miR‐9; as the phosphorylation of AKT increased, miR‐9 expression decreased. In addition, LY294002 increased miR‐9 expression. Taken together, our results indicated that simvastatin improved the migration of BMSCs via the PI3K/AKT pathway. MiR‐9 also participated in this process, and the phosphorylation of AKT affected miR‐9 expression, suggesting that simvastatin might have beneficial effects in stem cell therapy.
Development of nitrate tolerance is a major drawback to nitrate therapy. Prostacyclin (PGI2) is a powerful vasodilator produced from prostaglandin (PGH2) by prostacyclin synthase (PGIS) in endothelial cells. This study aimed to determine the role of PGIS S-nitrosylation in nitrate tolerance induced by nitroglycerin (GTN). In endothelial cells, GTN increased PGIS S-nitrosylation and disturbed PGH2 metabolism, which were normalized by mutants of PGIS cysteine 231/441 to alanine (C231/441A). Clearance of nitric oxide by carboxy-PTIO or inhibition of S-nitrosylation by N-acetyl-cysteine decreased GTN-induced PGIS S-nitrosylation. Enforced expression of mutated PGIS with C231/441A markedly abolished GTN-induced PGIS S-nitrosylation and nitrate cross-tolerance in Apoe mice. Inhibition of cyclooxygenase 1 by aspirin, supplementation of PGI2 by beraprost, and inhibition of PGIS S-nitrosylation by N-acetyl-cysteine improved GTN-induced nitrate cross-tolerance in rats. In patients, increased PGIS S-nitrosylation was associated with nitrate tolerance. In conclusion, GTN induces nitrate cross-tolerance through PGIS S-nitrosylation at cysteine 231/441.
Postoperative oxygenation impairment is a common complication of surgery for type-A acute aortic dissection. Body mass index, preoperative oxygenation impairment, preoperative homocysteine, circulatory arrest time, and plasma transfusion were independent risk factors for oxygenation impairment after a total arch replacement procedure.
Background Antegrade cerebral perfusion (ACP), including unilateral and bilateral, is most commonly used for cerebral protection in aortic surgery. There is still no consensus on the superiority of the two methods. Our research aimed to investigate the clinical effects of u-ACP and b-ACP. Methods 321 of 356 patients with type A aortic dissection were studied retrospectively. 124 patients (38.6%) received u-ACP, and 197 patients (61.4%) received b-ACP. We compared the incidence of postoperative neurological complications and other collected data between two groups. Besides, we also analyzed perioperative variables to find the potential associated factors for neurological dysfunction (ND). Results For u-ACP group, 54 patients (43.5%) had postoperative neurological complications, including 22 patients (17.7%) with permanent neurologic dysfunction (PND) and 32 patients (25.8%) with temporary neurologic dysfunction (TND). For b-ACP group, 47 patients (23.8%) experienced postoperative neurological complications, including 16 patients (8.1%) of PND and 31 patients (15.7%) of TND. The incidence of PND and TND were significantly different between two groups along with shorter CPB time (p = 0.016), higher nasopharyngeal temperature (p≦0.000), shorter ventilation time (p = 0.018), and lower incidence of hypoxia (p = 0.022). Furthermore, multivariate stepwise logistic regression analysis confirmed that preoperative neurological dysfunction (OR = 1.20, p = 0.028), CPB duration (OR = 3.21, p = 0.002), and type of cerebral perfusion (OR = 1.48, p = 0.017) were strongly associated with postoperative ND. Conclusions In our study, it was observed that b-ACP procedure exhibited shorter CPB time, milder hypothermia, shorter ventilation time, lower incidence of postoperative hypoxia, and neurological dysfunction compared to u-ACP. Meanwhile, the incidence of ND was independently associated with three factors: preoperative neurological dysfunction, CPB time, and type of cerebral perfusion.
Background: More evidence was required to guide the management of left subclavian artery (LSA) during thoracic endovascular aortic repair (TEVAR). The present study aimed to compare the outcomes of LSA coverage with LSA revascularization. Another purpose of this study was to share our experience of LSA revascularization with castor single-branched stent-graft. Methods: From January 2016 to December 2019, 134 patients with type B aortic dissection (TBAD) or intramural hematoma (IMH) were enrolled and divided into two groups, the LSA-covered group (n = 61) and the LSA-revascularized group (with castor single-branched stent-graft, n = 73). The results, such as in-hospital and 30-day mortality, stroke, paraplegia, left arm ischemia, operation time, endoleak, were compared between the two groups. Results: The incidence of 30-day stroke in the LSA-covered group (8.2%) was significantly higher compared with the LSA-revascularized group (0%, P = 0.018). 30-day ischemia of left arm occurred in more patients in the LSA-covered group (11.5%, P = 0.003). No statistical difference was found in the incidences of paraplegia, endoleak, in-hospital mortality, and 30-day mortality. Conclusions: LSA should be revascularized during TEVAR to reduce the incidences of stroke and left arm ischemia. Castor single-branched stent-graft was feasible and safe for treating TBAD or IMH.
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