Leng Ni

The protective effect of melatonin on smoke-induced vascular injury in rats and humans: a randomized controlled trial.

Smoking is one of the most harmful lifestyles in the world. Very few studies have investigated the effects of melatonin in smoke‐induced vascular injury. This study was designed to investigate whether melatonin could protect rats and humans from smoke‐induced vascular injury. 32 male rats and a double‐blind randomized controlled trial (RCT) containing 63 participants formed the subjects of this study. In rats, 10 mg/kg of melatonin was intraperitoneally injected. Blood samples and abdominal artery were harvested two weeks later. Melatonin decreased the expression of platelet endothelial cell adhesion molecule‐1 (CD31), intercellular adhesion molecule‐1 (ICAM‐1), vascular cell adhesion molecule‐1 (VCAM‐1) and endothelin‐1 (ET‐1) compared with the smoke exposed group (P < 0.05), whereas endothelial nitric oxide synthase (eNOS), nuclear erythroid 2‐related factor 2 (Nrf2), NAD(P)H quinone oxidoreductase 1 (NQO‐1), catalytic glutamate cysteine ligase (GCLC) and heme oxygenase‐1 (HO‐1) recovered markedly (P < 0.05). In humans, 3 mg/day of melatonin was taken orally by the participants. Blood samples were drawn at baseline and after two weeks of treatment. Compared with the oral placebo group, melatonin decreased the concentration of fibrinogen (Fbg) (P = 0.04) and free fatty acids (FFA) (P = 0.04) in smokers, along with the decreased expression of ICAM‐1, VCAM‐1 and ET‐1 (P = 0.004, P = 0.001, P < 0.0001, respectively). In contrast, Nrf2 and HO‐1 expression were markedly increased (P = 0.0001, P = 0.0049, respectively) after smokers took melatonin orally. In summary, our present data suggest that melatonin could ameliorate smoke‐induced vascular injury.

The p-ERK-p-c-Jun-cyclinD1 pathway is involved in proliferation of smooth muscle cells after exposure to cigarette smoke extract.

An epidemiological survey has shown that smoking is closely related to atherosclerosis, in which excessive proliferation of vascular smooth muscle cells (SMCs) plays a key role. To investigate the mechanism underlying this unusual smoking-induced proliferation, cigarette smoke extract (CSE), prepared as smoke-bubbled phosphate-buffered saline (PBS), was used to induce effects mimicking those exerted by smoking on SMCs. As assessed by Cell Counting Kit-8 detection (an improved MTT assay), SMC viability increased significantly after exposure to CSE. Western blot analysis demonstrated that p-ERK, p-c-Jun, and cyclinD1 expression increased. When p-ERK was inhibited using U0126 (inhibitor of p-ERK), cell viability decreased and the expression of p-c-Jun and cyclinD1 was reduced accordingly, suggesting that p-ERK functions upstream of p-c-Jun and cyclinD1. When a c-Jun over-expression plasmid was transfected into SMCs, the level of cyclinD1 in these cells increased. Moreover, when c-Jun was knocked down by siRNA, cyclinD1 levels decreased. In conclusion, our findings indicate that the p-ERK-p-c-Jun-cyclinD1 pathway is involved in the excessive proliferation of SMCs exposed to CSE.

Outcomes of vascular intervention and use of perioperative medications for nonpulmonary aneurysms in Behçet disease.

BACKGROUND Aneurysms attributable to Behçet disease (BD) are not common but are associated with a poor prognosis because of a high risk of rupture. Special considerations are required for vascular intervention, because the intense local inflammation may increase complications. The aim of this study was to assess the outcome of operative intervention and the use of perioperative medical therapy for aneurysms in patients with BD. MATERIALS AND METHODS We reviewed retrospectively the medical records of patients with BD admitted to Peking Union Medical College Hospital between January 1995 and January 2015. RESULTS Among 874 patients diagnosed with BD, 176 patients had vascular involvement, of whom 59 had arterial aneurysms. Thirty-six patients with 51 arterial aneurysms underwent operative intervention. The 51 primary operative interventions included 20 open operations and 31 endovascular interventions. Eleven (22 %) recurrent aneurysms developed in 10 patients and 5 (10%) thrombosis occurred in 5 patients. Of the 19 endovascular stents placed for aortic aneurysms, 1 type I endoleak, 1 graft occlusion, 3 recurrent aneurysms, and 1 recurrent aneurysmal rupture occurred. Among the revascularization procedures for extremity arteries, there were more complications with endovascular intervention than with open surgery. The cumulative risk of recurrent aneurysmal formation at the operative site was significantly less in patients treated with operative intervention combined with use of immunosuppressants than those treated with operative intervention alone (P = .01). CONCLUSION In patients with BD, an endovascular approach is feasible and effective for aortic aneurysms, whereas bypass surgery appears to provide better outcomes for extremity arterial aneurysms than placement of endovascular stents. The administration of corticosteroids combined with cyclophosphamide perioperatively decreases the cumulative risk of recurrent aneurysm.

Role of Thrombophilia in Premature Peripheral Arterial Obstructive Disease – Experience of a Vascular Centre in China

OBJECTIVE To evaluate aetiology profile and role of thrombophilia in patients with premature peripheral arterial obstructive disease (PAOD) in China. METHODS Between January 2000 and January 2010, among 368 patients presenting with PAOD, but not Buergers disease, at an age of less than 45 years, 150 patients have been screened for thrombophilia and the data analysed retrospectively. Aetiologies of thrombophilia which involved in premature PAOD were assessed and surgical outcomes were stratified for presence of thrombophilia. RESULTS In 57 of 150 patients (38%), laboratory assay results suggested thrombophilia, and the rest of them presented with other aetiology (62%). A total of 108 patients, including 38 patients with thrombophilia (35%), needed some type of revascularisation. At 30 days, recurrent thrombosis (29% vs. 9%; p = 0.005) and major amputations (11% vs. 1%; p = 0.032) were more common in patients with thrombophilia. At 1 year, primary patency (56% vs. 75%, p = 0.043), secondary patency (68% vs. 92%, p = 0.036) and limb salvage (74% vs. 96%, p = 0.038) were significantly lower in patients with thrombophilia. CONCLUSION Thrombophilia is frequently diagnosed among premature PAOD in China and adversely affects outcome after revascularisation. Clinicians should be aware of its high prevalence and aim at screening and sustained thrombophilia treatment.

Melatonin attenuates smoking‐induced hyperglycemia via preserving insulin secretion and hepatic glycogen synthesis in rats

Epidemiology survey indicated that cigarette smoking is a risk factor of diabetes. However, the precise mechanisms remain to be clarified. In this study, we found that smoking caused metabolic malfunctions on pancreas and liver in experimental animal model. These were indicated by hyperglycemia, increased serum hemoglobin A1c level and decreased insulin secretion, inhibition of liver glycogen synthase (LGS), and hepatic glycogen synthesis. Mechanistic studies revealed that all these alterations were caused by the inflammatory reaction and reactive oxygen species (ROS) induced by the smoking. Melatonin treatment significantly preserved the functions of both pancreas and liver by reducing β cell apoptosis, CD68‐cell infiltration, ROS production, and caspase‐3 expression. The siRNA‐knockdown model identified that the protective effects of melatonin were mediated by melatonin receptor‐2 (MT2). This study uncovered potentially underlying mechanisms related to the association between smoking and diabetes. In addition, it is, for first time, to report that melatonin effectively protects against smoking‐induced glucose metabolic alterations and the signal transduction pathway of melatonin is mainly mediated by its MT2 receptor. These observations provide solid evidence for the clinically use of melatonin to reduce smoking‐related diabetes, and the therapeutic regimens are absent currently.

Endovascular stenting for extracranial carotid artery aneurysms: Experiences and mid-term results

AbstractThe aim of this study was to investigate the safety and effectiveness of endovascular stenting for extracranial carotid artery aneurysms (ECAAs) and evaluate the mid-term outcomes.Twelve consecutive symptomatic patients (mean age 43.8 ± 14.9 years; 8 men) with ECAAs who were treated with endovascular stenting between 1997 and 2015 were retrospectively analyzed. Clinical follow-up data including symptoms and neurological events were obtained from outpatient records. Imaging follow-up with duplex ultrasound and/or computed tomographic angiography (CTA) was performed to examine the aneurysm obliteration and patency of the stents at 3, 6, 12 months and yearly thereafter.A total of 5 true aneurysms and 7 pseudoaneurysms were included in our series. Neurological symptoms (n = 5, 41.7%) and a pulsatile neck mass (n = 5, 41.7%) were the most common presenting symptoms. Endovascular stenting procedures were technically successful in all cases; 3 patients received bare stents, and 9 patients received covered stents. No perioperative neurologic or cardiopulmonary complications occurred. Over a period of follow-ups (mean 21.8 ± 25.1 months), all patients were alive and free from neurological or other adverse events. All aneurysms were completely excluded except for 1 patient who was exposed to a residual medium leaking into the aneurysm sac. No reintervention was performed in this specific patient because aneurysm growth or significant clinical symptoms did not occur. Recurrent restenosis assessed by CTA imaging at 12 months occurred in 1 (8.3%) patient in our series. Target lesion revascularization for this hemodynamic restenosis was treated with placement of an additional stent.In our series, endovascular stenting for ECAAs was found to be safe, effective, and proved to have promising mid-term results. Although long-term results need to be further explored, advantages including less procedure-related complications and a shorter recovery time make endovascular stenting an attractive option for ECAAs, especially for the patients who are unfit for traditional open surgery.

The effect of soy or isoflavones on homocysteine levels: a meta‐analysis of randomised controlled trials

BACKGROUND The present study aimed to evaluate the effect of soy or isoflavones on blood homocysteine levels via a systematic review and meta-analysis. METHODS Pubmed, Embase, Web of Science and the Cochrane Library (up to 16 December 2015) were used for the literature review. Only randomised controlled trials were included. The primary outcome was the standard mean difference (SMD) of blood homocysteine levels between the experimental and control groups. RESULTS Nineteen randomised controlled studies were included for qualitative analysis. Eighteen studies were included in the data synthesis. Soy or isoflavones were found to have no effect on homocysteine levels, with a SMD of -0.21 (95% confidence interval = -0.43 to 0.00, I2 =67.7%, random effect model). No publication bias was found among those studies (P = 0.296 for Eggers test, and P = 0.198 for Beggs test). CONCLUSIONS Soy or isoflavones were not found to be associated with a reduction in homocysteine levels. Further studies might still be needed in carefully selected populations.

Sulodexide recovers endothelial function through reconstructing glycocalyx in the balloon-injury rat carotid artery model

Disruption of endothelial cell function is a principle event in cardiovascular disease. Accordingly, therapies have mostly focused on repairing the endothelium, but little attention has been paid to the reconstruction of glycocalyx, which covers the endothelium and protects the function of endothelial cells. Sulodexide has a similar glycosaminoglycan structure to glycocalyx, so it is assumed to be effective in remodeling the glycocalyx following damage. We assessed the effect of sulodexide on glycocalyx remodeling and endothelial function in the balloon-injury rat carotid artery model. Electron micrographs showed that sulodexide (2mg/kg, administered by intraperitoneal injection for seven days after injury) could reconstruct the endothelial glycocalyx and recover the clear cytoarchitecture. With regard to endothelial function, sulodexide increased endothelial nitric oxide synthase level, attenuated endothelial hyperplasia, and inhibited platelet aggregation that benefitted from glycocalyx reforming. Sulodexide decreased the glycocalyx damage related expression of CD31 and intercellular cell adhesion molecule-1 in endothelium, accompanying by the downregulation of leukocyte counts and C-reactive protein levels. The levels of the atherosclerosis-related factors, osteopontin and vascular cell adhesion molecule-1, which increased in activated endothelial cells lacking glycocalyx, were normalized by sulodexide. Along with the benefit of glycocalyx reconstruction, sulodexide reversed the dyslipidemia. Moreover, sulodexide prevented CD68-positive inflammatory cells infiltration into the vascular wall, presumably as a result of glycocalyx reconstruction. In summary, sulodexide treatment reconstructed glycocalyx which therefore preserved endothelial function and attenuated the expression of inflammatory factors, and decreased the blood coagulation and lipid metabolism, all of which are important for vascular healing.

Prediction of Cerebral Hyperperfusion Syndrome with Velocity Blood Pressure Index.

Background:Cerebral hyperperfusion syndrome is an important complication of carotid endarterectomy (CEA). An >100% increase in middle cerebral artery velocity (MCAV) after CEA is used to predict the cerebral hyperperfusion syndrome (CHS) development, but the accuracy is limited. The increase in blood pressure (BP) after surgery is a risk factor of CHS, but no study uses it to predict CHS. This study was to create a more precise parameter for prediction of CHS by combined the increase of MCAV and BP after CEA. Methods:Systolic MCAV measured by transcranial Doppler and systematic BP were recorded preoperatively; 30 min postoperatively. The new parameter velocity BP index (VBI) was calculated from the postoperative increase ratios of MCAV and BP. The prediction powers of VBI and the increase ratio of MCAV (velocity ratio [VR]) were compared for predicting CHS occurrence. Results:Totally, 6/185 cases suffered CHS. The best-fit cut-off point of 2.0 for VBI was identified, which had 83.3% sensitivity, 98.3% specificity, 62.5% positive predictive value and 99.4% negative predictive value for CHS development. This result is significantly better than VR (33.3%, 97.2%, 28.6% and 97.8%). The area under the curve (AUC) of receiver operating characteristic: AUCVBI= 0.981, 95% confidence interval [CI] 0.949–0.995; AUCVR= 0.935, 95% CI 0.890–0.966, P = 0.02. Conclusions:The new parameter VBI can more accurately predict patients at risk of CHS after CEA. This observation needs to be validated by larger studies.

The protective effect of melatonin on brain ischemia and reperfusion in rats and humans: In vivo assessment and a randomized controlled trial

Carotid endarterectomy (CEA) is the treatment of choice for carotid stenosis. Some patients develop ischemia and reperfusion (I/R) injury after CEA. This study was designed to investigate the neuroprotective effects of melatonin on I/R injury in both rats and humans. To this end, 36 male rats were evaluated, and a double‐blind randomized controlled trial (RCT) including 60 patients was performed. A rat model of middle cerebral artery occlusion was used to mimic cerebral I/R. After 2 hour of occlusion and 24 hour of reperfusion, blood samples and brain tissues were harvested for further assessments. Compared with the vehicle treatment, melatonin decreased the expression of nuclear factor κ light‐chain‐enhancer of activated B cells (NF‐κB) and S100 calcium‐binding protein β (S100β) (P < 0.05) and markedly increased the expression of nuclear erythroid 2‐related factor 2 (Nrf2), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) (P < 0.05). The participants in the RCT took 6 mg/d melatonin orally from 3 days before surgery to 3 days after surgery. Blood samples were drawn at the following times: baseline; pre‐anesthesia; carotid reconstruction completion; and 6, 24, and 72 hour after CEA. Compared with the oral placebo treatment, melatonin decreased the expression of NF‐κB, tumor necrosis factor‐α, interleukin‐6 (IL‐6), and S100β (P < 0.05) and increased the expression of Nrf2, SOD, CAT, and GPx (P < 0.05) in patients after CEA. Our findings suggested that melatonin could ameliorate brain I/R injury after CEA and that this outcome was essentially due to the antioxidant and anti‐inflammatory effects of melatonin.