Cardiovascular disease is a leading cause of death in Chinese population. It is of great significance to further explore the pathogenesis of cardiovascular diseases. Ferroptosis is a recently discovered iron-dependent and non-apoptotic form of regulated cell death, which exerts a regulatory role in a variety of biological events. Some studies have shown that ferroptosis plays an important role in the development of cardiovascular diseases. According to newly scientific reports, we summarized the mechanism and regulation in ferroptosis, and reviewed the results of ferroptosis in common cardiovascular diseases such as cardiac ischemia-reperfusion/myocardial infarction, cardiomyopathy, cardiac hypertrophy, atherosclerosis and abdominal aortic aneurysm.
【Abstract】ObjectiveTo investigate the effects of As2O3 on expression of NF-κB p65, survivin and caspase-3 in human breast infiltrating duct carcinoma xenograft model on nude mice. Methods A human breast infiltrating duct carcinoma model on nude mice was established and the nude mice were divided randomly into three groups: control group, DDP group and As2O3 group （1.5 and 3.0 mg/kg concentrations）. The expression of survivin mRNA was detected with the method of in situ hybridization and the expressions of NF-κB p65, survivin and caspase-3 protein were measured with immunohistochemistry. ResultsThe positive rates of NF-κB p65 and survivin expression were higher in the control group than those in the DDP group and the As2O3 groups, but that of caspase-3 was on the opposite way (P＜0.01). The positive rates of NF-κB p65 and survivin in As2O3 group were negatively related with the concentrations of As2O3 (P＜0.01), but that of caspase-3 was on the opposite way (P＜0.01). The expressions of NF-κB p65 and survivin protein were positively correlated with that of survivin mRNA, but any of them was negatively correlated with the expression of caspase-3 protein. ConclusionAs2O3 inhibites survivin probably by inhibiting the activity of NFκB p65 and subsequently activates caspase-3, which induces apoptosis of human breast infiltrating duct carcinoma cells and is in a dose-dependent manner.
Abstract: Objective To observe the expression of integrinlinked kinase (ILK) and matrix metalloproteinases9 (MMP9) in human nonsmall cell lung cancer (NSCLC) and investigate the correlation of ILK and MMP9 expression with the prognosis of NSCLC. Methods The expression of ILK and MMP9 in 75 specimens of NSCLC resected from January 2002 to January 2004 were detected by immunohistochemistry. According to the median of integral optical density (IOD), all patients were divided into the high or low ILK expression group and the high or low MMP-9 expression group. The relativity of ILK and MMP9 was determined, and the relationship of survival time with clinical features including expression of ILK and MMP-9 was compared by Logrank test. Results Both ILK and MMP-9 were expressed in NSCLC specimens. The expression between ILK and MMP-9 was positively correlated in 75 patients of our group (r=0.79, Plt;0.05). Patients with lower expression of ILK and MMP9 had a significantly longer survival time than those with higher expression of ILK and MMP-9 in the postoperative followup (χ2=15.067,14301,Plt;0.05). The survival time was not correlated with sex,age,smoking history or pathological type(χ2=0450,0078, 1.460, 1.623，Pgt;0.05), while tumor diameter, lymph node metastasis, TNM stage, the expression of ILK and MMP-9 significantly influenced the survival time (χ2=3.963, 15.169,20.529, 15.067，14.301，Plt;0.05). Conclusion The expression of ILK and MMP9 affects the prognosis of NSCLC. MMP-9 may advance infiltration and metastasis of tumor cells through ILK pathway. In summary, the expression of ILK and MMP9 may play an important role in the evaluation of prognosis for patients with NSCLC.
Objective To summarize and analyze the clinical experience and surgical results of re-do coronary artery bypass grafting (Re-CABG) for reconvert coronary artery disease. Methods Eighteen patients who underwent Re-CABG in this hospital between June 2001 and December 2006 were analyzed. There were 15 males and 3 females aged from 65 to 78 years old. Seven patients were in class III angina(CCS) and 11 patients were in class IV. Coronary artery angiography showed stenosis or occlusion of great saphenous vein grafts in 16 patients, occlusion of left internal mammary artery(LIMA) grafts in 2 patients and new significant stenosis of the native coronary artery in 6 patients. All Re-CABG were done through re-sternotomy. Fifteen patients underwent cardiopulmonary bypass (CPB for their Re-CABG and 3 patients underwent off-pump Re-CABG. The concomitant procedures included left ventricular aneurysmectomy in 1 patient, mitral valve repair in 3 patients, combined aortic and mitral valve replacement and carotid endarterectomy in 1 patient. Bilateral IMA were used in 4 patients, LIMA in 12 patients, radial artery in 3 patients, and the rest of the grafts consisted of great and lesser saphenous vein. Results In on-pump Re-CABG, the aortic cross clamp time was 57±26min (range 45 to 112 min), the CPB time was 78±24min (range 66 to 140 min).The mean number of distal anastomosis per patient was 3.11(range 1 to 5). Intraoperative flow study of the grafts by Medi-Stim Butterfly showed a mean flow rate of 27.0±12.5 ml/min with pulsatility index( PI)less than 4.2. Intra-aortic balloon pump (IABP) was used in 1 patient who underwent concomitant aortic and mitral valve replacement and carotid endarterectomy. Post-operatively this patient developed renal failure and expired 6 days later. There was no residual angina and peri-operative myocardial infarction in the remain 17 patients.The post-operatively mechanical ventilation time varied from 5 to 15 hours, chest drainage varied from 290 to 1 040ml. Seventeen patients were discharged uneventfully. Follow-up from 6 months to 4.5years in 17 patients showed no evidence of recurrent angina. Postoperative coronary artery angiography in 4 patients showed patent grafts. Conclusion Re-CABG can be performed as safely and effectively as primary CABG in spite of the fact that it is more demanding. Selecting the proper target vessels, satisfactory blood flow of grafts, complete revascularization and proper peri-operative management are all key factors to a successful Re-CABG.
ObjectiveTo analyze the clinical effects of allograft orthotopic heart transplantation.MethodsThe clinical data of 36 patients with allograft orthotopic heart transplantation performed in the Heart Centre of Nanjing First Hospital from January 1, 2014 to January 1, 2019 were retrospectively analyzed. There were 31 males and 5 females, aged 23-65 (46.2±8.8) years. Protopathy diseases of recipients included dilated cardiomyopathy in 33 patients, end-stage coronary heart disease in 2 patients, and end-stage valvular heart disease in 1 patient. Heart transplantations were performed through double vena cava anastomosis. Immune induction during operations was treated with a combination therapy of both bariximab and methylprednisolone. Postoperatively, all patients were treated with a new triple immunosuppression protocol: FK506+cellcept+prednisone.ResultsDuring the perioperative period, 1 patient died of severe infection. For 8 patients with heart failure, after adjustment and intra-aortic balloon pump, the cardiac function of all the 8 patients improved. For 5 patients with renal failure, after continuous renal replacement therapy, the renal function of all the patients returned to normal. One patient died of graft failure after 1 year of follow-up. The follow-up time for each patient postoperatively differed from 3 to 49 months with an average time of 16±4 months while the 1-year survival rate was 97.1% (34/35). Among them, 10 patients were marginal donors, with no significant differences between conventional donors and them. Conclusion For end-stage heart diseases, heart transplantation is one of the effective treatment methods in China with fine early- and middle-term curative effects. Reasonable application of intra-aortic balloon pump, continuous renal replacement therapy and other adjuvant treatments and the new triple immunosuppression protocol can significantly improve the success rate of heart transplantation, reduce the occurrence of acute and chronic rejections. The application of marginal donors can alleviate the current situation of shortage of donors to some extent.
Objective To investigate the risk factors of grafts stenosis following coronary artery bypass grafting (CABG), in an effort to benefit the prevention and treatment of graft stenosis after CABG. Methods The clinic data of 197 patients who underwent CABG and received selective angiography between January 1999 and December 2007 were retrospectively analyzed and all patients were subdivided into stenosis group (n=87) and normal group(n=110). Statistic analysis of χ2 test, ttest and multiple logistic regressions were used to find out the risk factor. Results It was demonstrated by angiography that there was graft stenosis after CABG in 87 patients involved 321 stomas (305 in the distal and 16 in the proximal). Univariate analysis revealed that diabetes mellitus，dyslipidemia, distal anastomoses in right coronary artery (RCA) territory, ＜70% stenosis in target coronary artery, ＜1.5 mm in diameter in target artery, saphenous vein grafts(SVG) and offpump CABG were significantly related to stenosis of grafts following CABG, and logistic multivariate regression analysis showed that diabetes mellitus(OR=3.654)， dyslipidemia(OR=2.625), distal anastomoses in RCA(OR=1.694), ＜70% stenosis in target coronary artery(OR=1.763), ＜1.5 mm in diameter in target artery (OR=1.337)and utilization of SVG (OR=1.652) were independent risk factors of graft stenosis. Conclusion Diabetes mellitus，dyslipidemia, distal anastomoses in RCA, ＜70% stenosis in target coronary artery, ＜1.5 mm in diameter in target artery and utilization of SVG are the risk factors of graft stenosis following CABG.
Objective To summarize the early outcomes and clinic al experience of off-pump coronary artery bypass grafting (off-pump CABG) afte r off-pump coronary endarterectomy (CE) for patients with diffused coronary art ery disease. Methods From May 2003 to November 2006，83 patients with diffu sed coronary artery disease underwent CE without cardiopulmonary bypass and off-pump CABG. There were 61 males and 22 females with age ranged from 55 to 80 ye ars (65±7 years). There were 7 patients in Canadian Cardiac Society(CCS) an gina classⅡ,20 patients in class Ⅲ,and 56 patients in class Ⅳ. 36(43.4%) pat ients had history of myocardial infarction. Coronary angiogram revealed th at 5 patients had double vessels disease, and other 78 patients had triple ves s els disease with 16 left main stem disease. The left ventricular ejection fract ion(LVEF) ranged from 25% to 65% (51%±16%). One hundred and ten endarter e ctomies were performed in 83 patients totally which included 67 in left anterior descending artery(LAD)，9 in circumflex artery and 34 in right coronary artery . Twenty patients received onlay venous patch after CE in LAD and then grafte d by internal mammary artery (IMA) on the patch. There were 83 left IMA, 2 radia l arteries, others were great saphenous veins, the mean number of grafts was 3.9 ±1.2. Results There was no death in all patients. Intraoper ative graft flowmeter was used to check the flow in the grafts before chest cl osure. One hundred and one (92%) out of 110 grafts after CE showed a satisfactor y grafts flow(22±16ml/min) intraoperatively. Four patients had perioperative myocardial infarctions but none had hemodynamic changes. All patients discharged uneventfully. Seventyfive patients (90.4%) had 8 to 50 months followup with no angi na reoccurrence. Eight patients had coronary angiogram from 3 to 29 months af ter operation with all patent grafts to the CE coronaries. Conclusion Off-pump CABG with coronary endarterectomy is feasible and achieves surgical revascularization in patients with diffuse cor onary artery disease.
Objective To investigate the effect of combined carotid endarterectomy (CEA) and offpump coronary artery bypass grafting (OPCAB) on patients with carotid arteriostenosis and coronary heart diseases. Methods A total of 121 consecutive patients with carotid arteriostenosis and coronary artery diseases underwent CEA and OPCAB between January 2003 and December 2009 in Nanjing First Hospital of Nanjing Medical University. There were 81 males and 40 females, with their ages ranged from 62 to 72 years (67.2±4.5 years). All patients had 3vessel coronary artery lesions, and there were 3 cases of left main coronary artery lesion. Unilateral carotid arteriostenosis (≥50%) occurred in 95 patients, and bilateral (≥50%) in 26 patients. The occurrence of stroke, myocardial infarction, angina pectoris and other complications after operation was observed, and followup was carried out. Results All patients underwent unilateral CEA including 50 on the right side and 71 left. The mean block time of carotid artery in CEA was 20.5±7.0 minutes. The average number of distal grafts per patient in OPCAB was 2.9±0.3. None of the patients had stroke or myocardial infarction and no perioperative death occurred. Eightyseven patients felt well in terms of their neuropsycho symptoms; 32 felt no change; and 2 worsened. Follow-up was done for all the patients with a follow-up rate of 100%. The mean time of the follow-up was 67.5±12.5 months. During this period, none of the patients manifested stroke, myocardial infarction or neuropsycho symptoms. Conclusion Concomitant OPCAB and CEA is a safe and effective procedure in patients with carotid arteriostenosis and coronary artery diseases. It can reduce the rate of postoperative stroke significantly. However, longterm outcome of the procedure needs operative experience accumulation, longterm follow-up and observation, and serious research and illumination.
Objective To investigate the dose-dependent relationship of bone marrow mesenchymal stem cells(MSCs) transplantation in improving ischemic myocardial dysfunction? in a rat ischemic heart model. Methods Myocardial infarction was induced in 32 inbred F344 rats by acute ligation of the left anterior descending(LAD) coronary artery. One week after ligation, the ratswere randomized? into four equal groups, with eight rats in each group. Equal volume Iscove’s modified Dulbecco’s medium was injected in the control group, 1×103(group 1), 1×105(group 2), and 1×107(group 3) 5-bromodeoxyuridine (BrdU) labeled bone marrow MSCs were injected into the infarcted myocardium. Cardiac function was evaluated by ultrasound before the ligation of the LAD, before the transplantation and the 4th week after transplantation. The expressions of BrdU,Connexin43,Myosin heavy chain β(MHC), and smooth muscle actin α(α-SMA) were detected by immunofluorescence and immunohistochemistry at the 4th week after transplantation. The amount of functional vessels stained by α-SMA was counted simultaneously. Results At the 4th week? after transplantation, the ejection fraction(EF) in goup 2 was more significantly improved than that in group1(0.54±0.20 vs. 0.34±0.16, P＝0.004) and EF in group 3 was more significantly improved than that in group 2(0.71±0.24 vs. 0.54±0.20,P＝0.018), whereas no significant difference between group 1 and control group was detected (0.34±0.16 vs. 0.36±0.15,Pgt;0.05). The BrdU labeled MSCs could be found in host myocardium. The number of cells in group 2 by double staining both for BrdU and for MHC observed in ischemic myocardium were significantly more than that in group 1? (323.20±91.62 n/HP vs. 51.75±27.58 n/HP,P＝0.049) and the same was true between group 3 and group 2(409.75±106.65 n/HP vs. 323.20±91.62 n/HP,Plt;0.001), whereas the result of control group was negative.The majority of transplanted cells were found positive staining both for MHC and for Connexin43 in all groups. There were lots of positive staining of α-SMA whose form were partly irregular in ischemic myocardium indicating that there was neovascularization in group1 and control group. More neovascularization in group2 was found than that in group 1 (28.38±12.79 n/HP vs. 22.75±9.07 n/HP, P＝0015) and more neovascularization in group 3 was found? than that in group 2 (35.63±13.27 n/HP vs. 28.38±12.79 n/HP, P＝0.002) . Conclusion Transplanted into infarcted myocardium, bone marrow MSCs may have significant and dose-dependent potential for cardiomyogenesis with functional recovery from myocardial ischemia.