1.Transdifferentiation of mesenchymal stem cells isolated from the rabbit mobilized peripheral blood into cardiomyocytes in vitro
Hongwei LIU ; Luyue GAI ; Duanzhen ZHANG
Basic & Clinical Medicine 2006;0(01):-
Objective To isolate mesenchymal stem cells(MSCs) from the mobilized peripheral blood and transdifferente them into cardiomyocytes for establishing an non-invasive cell source of stem cell transplantation for myocardial infarction therapy.Methods To granulocyte-colony stimulating factor((30 ?g/kg?day)) was injected into New Zealand White rabbits subcutaneously for 5 days,then MSCs were isolated from peripheral blood.After treatment with 5-azacytidine for 24 hours,the cultured cells were evaluated by immunohistochemical staining for actin,desmin and cardiac-specific troponin T(cTNT).Results After treatment with 5-azacytidine,the MSCs from the mobilized peripheral blood showed spindle-like and multinucleation,some cells aggregated and formed a ball-like appearance at 2 weeks.The ball-like cells and some spindle-like multinuclear cells were found with positively staining of actin,desmin and cTNT.Conclusion MSCs can be isolated from the mobilized peripheral blood and transdifferented into cardiomyocytes in vitro,suggesting that MSCs from the mobilized peripheral blood may be a new and non-invasive cell source of stem cell transplantation in myocardial infarction therapy.
2.Change of estrogen in patients with pulmonary artery hypertension secondary to congenital heart disease
Hongmei XUE ; Xianyang ZHU ; Duanzhen ZHANG ; Jing MENG
Chinese Journal of Postgraduates of Medicine 2009;32(21):13-16
Objective To study the change of estrogen in patients with pulmonary artery hypertension (PAH) secondary to congenital heart disease (CHD). Methods A total of 144 patients with CHD including 36 patients with normal pulmonary arterial pressure as control group, and 108 with PAH were investigated as PAH group. Their pulmonary artery pressure was measured by right heart catheterization and the serum concentrations of estradiol, progesterone, prolactin and follicle stimulating hormone (FSH) were detected by chemiluminescence immunoassay. Results The serum concentrations of estradiol, progesterone, prolactin and FSH in PAH group were significantly higher than those in control group (P<0.05). Multiple regression analysis showed that the concentrations of estradiol, progesterone and prolactin were not correlated with the site of shunt but significantly correlated with physiologic factor including sex, age and menstrual cycle, and the level of mean pulmonary arterial pressure. The correlation coefficient of mean pulmonary arterial pressure to them was 0.607,0.531 and 0.518 respectively. The concentration of FSH was positively correlated with the prolactin and estradiol with a related coefficient of 0.917 (P=0.012) and 0.759 (P= 0.000). Conclusion The estrogen plays an important role in modification of the pulmonary arterial pressure in patients with CHD and PAH.
3.Comparison between mobilization and transplantation of bone marrow stem cells for the therapy of myocardial infarction in rabbits
Hongwei LIU ; Luyue GAI ; Duanzhen ZHANG ; Qinhua JIN ; Wei DONG
Chinese Journal of Pathophysiology 1986;0(04):-
AIM: To compare bone marrow stem cell mobilization with bone marrow-derived mononuclear cells (BMCs) transplantation for the therapy of myocardial infarction (MI) in rabbits, and to explore more effective and practical stem cell therapeutic strategy for MI. METHODS: In mobilization group (M, n=10), granulocyte-colony stimulating factor (G-CSF) (30 ?g?kg~ -1 ?d~ -1 ) was injected subcutaneously 3 hours after MI and every 24 hours for 5 days. On the 5th day, the BMCs from 10 mL peripheral blood were labeled with bromodeoxyuridine (BrdU) for 24-48 hours, then reinjected intravenously. In transplantation group (T, n=10), BMCs transplantation was performed 5-7 days after MI. After being obtained from bone marrow (3- 5 mL ) of iliac crest and labeled with BrdU for 24-48 hours, BMCs were transplanted into infracted myocardium through intramyocardial injection. Control animals (C, n=10) did not receive any treatment after MI. Echocardiography were performed for the evaluation of cardiac function 1 week and 5 weeks after MI. Hemodynamic studies and histological study were performed 5 weeks after MI. RESULTS: LV ejection fraction increased significantly in group M, had no change in group T, and decreased 1 week and 5 weeks after MI in group C. Group M and group T had higher LV max +dp/dt and max -dp/dt, lower LV end-diastolic pressure compared with group C 5 weeks after MI. Histological studies revealed that there were BrdU positive cells in the infarcted area in group M and group T. The vascular density of group M and group T in the infarcted area was significantly greater in comparison with group C. No regeneration of smooth muscle cells and cardiomyocytes were found in the infarcted area. CONCLUSION: Bone marrow stem cell mobilization with G-CSF and transplantation of BMCs both significantly improve the cardiac function for the therapy of MI through vascular genesis in the infarcted area. Bone marrow stem cell mobilization may offer a new and non-invasive therapeutic strategy for MI.
4.Risk factors and early diagnosis of severe thrombocytopenia complicating transcatheter occlusion of a ;patent ductus arteriosus
Po ZHANG ; Xianyang ZHU ; Duanzhen ZHANG ; Qiguang WANG ; Xiumin HAN ; Xiaotang SHENG ; Chunsheng CUI
Chinese Journal of Interventional Cardiology 2016;24(1):23-27
Objective To investigate the risk factors and early diagnosis of the severe thrombocytopenia complicating transcatheter ccclusion of patent ductus arteriosus ( PDA ) . Methods Between February, 2011 and May, 2015, 80 patients with patent ductus arteriosus underwent percutaneous intervention occlusion were studied. Results Average age were ( 17. 5 ± 17. 1 ) years, 63 were females (78. 8%), mean weight were (35. 6 ± 20. 2)kg (from 6. 0 to 75. 0 kg), mean body surface area (BSA) were (1. 09 ±0. 44) m2(from 0. 32 to 1. 91 m2). A bolus of heparin calcium (80 U/kg) was administered by intravenous injection. The mean diameters of patent ductus arteriosus were 4 mm (from 2 to 18 mm), and the mean diameters of occluders were 12 mm (from 6 to 30 mm). 14 patients were found to have severe thrombocytopenia (PLT count﹤100 × 109/L). The reduction rate of platelet in 12 of 14 patients was more than 19%. The diameters of all occluders were equal to or more than 14 mm, the mean diameters of patent ductus arteriosus were 10 mm ( from 6 to 18 mm) and the mean diameters of occluders were 18 mm ( from 14 to 30 mm). All the 14 patients started to present progressive decrease in PLT count since the second day post procedure. Taking the selected occluder diameter greater than 14 mm as cut-off points in diagnosis of severe thrombocytopenia, the sensitivity was 100%, specificity was 68%, the positive predictive value was 40%, and the negative predictive value was 100%. Combined with the postprocedural second day complete blood count analysis and the platelet count decreased by 10% as cut-off points in diagnosis of severe thrombocytopenia patients, the sensitivity was 93%, specificity was 67%, the positive predictive value was 65%, the negative predictive value was 93% . If taking the platelet count decreased by 7% on second day as cut-off points in diagnosis of severe thrombocytopenia patients, the sensitivity was 100%, specificity was 57%, the positive predictive value was 61%, the negative predictive value was 100% . Logistic regression analysis discovered that risk factors of severe thrombocytopenia after PDA are procedural platelet count and occluder diameter. Conclusions The risk factors of severe thrombocytopenia complicating transcatheter ccclusion of patent ductus arteriosus were the procedural reduction of platelet count and big occluder diameter. Patients with PDA who were inplanted with occluders equal to or bigger than 14 mm should retest the numbers of platelet on the second day after procedure and retest on third day if the numbers reduce on the second day, which may help in the prediction of severe thrombocytopenia.
5.Influence of simvastatin on differentiation, proliferation, migration and adhesion of smooth muscle progenitor cells
Yanxia LIU ; Lan HUANG ; Xianyang ZHU ; Po ZHANG ; Duanzhen ZHANG ; Xiumin HAN ; Qiguang WANG
Chinese Journal of cardiovascular Rehabilitation Medicine 2014;23(5):519-522
Objective:To observe influence of simvastatin on differentiation ,proliferation ,migration and adhesion of marrow-derived smooth muscle progenitor cells (SPCs) and screen coated eluting stent drugs of new generation . Methods :The mononuclear cells (MNCs) were isolated from rat marrow by density gradient centrifugation method , and then plated on fibronectin-coated culture dishes ,after culture 8d ,marrow-derived SPCs were identified by α-smooth muscle actin (α-SMA) immunofluorescent staining and counted under inverted fluorescence microscope .The MNCs and adhesion cells were treated with simvastatin (0.01~10 μmol/L) respectively for 8 d and 24h .SPCs pro-liferation ,migration and adhesion were observed by Tritium thymidine (3 H-TdR) intake method ,modified Boyden chamber assay and adhesion assay .Results:Compared with control group (no simvastatin intervention ) ,0.01μmol/L simvastatin significantly inhibited the MNCs differentiation towards SPCs [ (85 ± 4) vs .(79 ± 5)] ,proliferation [ (4070 ± 184) vs .(3833 ± 126)] ,migration [ (44 ± 3) vs .(39 ± 3)] and adhesion of SPCs [ (59 ± 5) vs .(52 ± 4)] , P<0.05 all ,and number of SPCs significantly reduced along with simvastatin concentration increased (P<0.01) . Conclusion:Simvastatin could inhibit the differentiation ,proliferation ,migration and adhesion of marrow-derived smooth muscle progenitor cells .
6.Expressions of endothelin-1 in primary cultured atrial myocytes during early rapid pacing
Yanxia LIU ; Po ZHANG ; Xianyang ZHU ; Xiumin HAN ; Duanzhen ZHANG ; Qiguang WANG
Chinese Journal of cardiovascular Rehabilitation Medicine 2012;21(4):341-345
Objective: To study the expressions of endothelin-1 in primary cultured atrial myocyte model at early stages of atrial fibrillation by rapid pacing. Methods: The primary rat atrial myocytes were cultured, in which a rapid paced cell model was established. The polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) were applied to detect the messenger ribonucleic acid (mRNA) expression and secretion of endothelin-1 on 3 h, 6 h, 12 h and 24 h after rapid pacing. Results: Compared with before pacing, there were continuous and significant increase in expression of ET-1mRNA [ (0.31±0.02) vs. (0.52±0.07), (0.62±0.09), (0.75±0.05) ] and secretion of endothelin-1 [ (3.4±0.8) ng/L vs. (6.0±1.4) ng/L, (8.3±1.5) ng/L, (11.2±2.1) ng/L] on 6 h, 12 h and 24 h after rapid pacing, P<0.01 all. Conclusion Expressions of ET-1mRNA and secretion of endothelin-1 significantly increase depend on time in early rapid pacing atrial myocytes, indicating that endothelin-1 participates in atrial pathological remodeling during atrial fibrillation.
7.Relationship between the size of ostium secundum atrial seplal defect and the pulmonary arterial pressure in children less than 5 years of age
Po ZHANG ; Xianyang ZHU ; Duanzhen ZHANG ; Qiguang WANG ; Xiumin HAN ; Xiaotang SHENG ; Chunsheng CUI
Journal of Interventional Radiology 2014;(7):565-568
Objective to investigate the relationship between the size of ostium secondary atrial septal defect (ASD) and the pulmonary arterial pressure (PAP) in children less than 5 years of age. Methods During the period from April 2000 to January 2011, a total of 189 child patients less than 5 years of age with ostium secondary ASD were admitted to General Hospital of Shenyang Military Command. Under general anaesthesia with ketamine cardiac catheterization was performed, PAP was measured, and percutaneous occlusion of ASD was carried out in all patients. The clinical indexes, including sex, age, body height, body weight, body surface area, diameter of ASD defect, heart- to- thorax ratio, the systolic, diastolic and mean pressure of the pulmonary artery, etc. were determined. The patients were followed up for one year and postoperative cardiac ultrasonography was performed to check the results. The patients were divided into groups according to the defect size. Results The 189 patients consisted of 77 males and 112 females with a male-to-female ratio of 1 ∶ 1.5. The mean age was (4.1 ± 0.9) years old, ranging from 2 to 5 years old. The mean weight was (17.2 ± 3.6) kg, ranging from 10.0 to 30.0 kg. The mean height was (104.9 ± 9.2) cm, ranging from 77 to 135 cm. The mean body surface area (BSA) was (0.71 ± 0.10) m2, ranging from 0.46 to 1.02 m2. The mean size of ASD was (12.6 ± 4.8) mm, ranging from 5 to 29 mm. The mean size of ASD, which was modified by BSA, was (18.0 ± 7.0) mm/m2, ranging from 5.3 to 38.9 mm/m2. The mean systolic PAP was (41.1 ± 8.9) mmHg with a range of 15 - 67 mmHg. The mean diastolic PAP was (16.8 ± 6.5) mmHg with a range of 3 - 45 mmHg. The mean PAP was (24.9 ± 6.7) mmHg with a range of 12 - 48 mmHg. One hundred and fifty- nine patients (89.4%) had pulmonary arterial hypertension (PAH) which was determined by right heart catheterization, but no patient showed PAH when the pulmonary arterial pressure was measured by echocardiography before the procedure as well as 1, 3, 6, 12 months after the procedure. No definite correlation existed between the size of ASD and the pulmonary artery pressure (P > 0.05). Conclusion Pulmonary artery pressure measured by right heart catheterization has no definite correlation with the size of ASD in children less than 5 years of age. Pulmonary artery pressure obtained from right heart catheterization is higher than that determined by cardiac ultrasonography, which may be caused by the effect of ketamine when general anaesthesia is used in performing right heart catheterization.
8.Curative effect of fenestrated occluders in atrial septal defects with severe pulmonary arterial hypertension
Huoyuan CHEN ; Xianyang ZHU ; Xiaotang SHENG ; Duanzhen ZHANG ; Qiguang WANG ; Xiumin HAN ; Chunsheng CUI ; Jingsong GENG
Chinese Journal of Interventional Cardiology 2015;(11):601-605
Objective To evaluate clinical effectiveness of transcatheter closure of atrial septal defects ( ASD) with severe pulmonary arterial hyperyension ( sPAH) by fenestrated Amplatzer septal occluders ( ASO) . Methods From September 2002 to April 2013, 17 patients of ASD with sPAH received transcatheter ASD closure using fenestrated occluders. Aged from 18 - 72 years, the diameters of ASDs were 18 - 33 mm. The systolic pulmonary arterial hypertension measured by transthoracic echocardiogram were 80 - 112 (96. 9 ± 8. 9) mmHg. The follow-up study included electrocardiography, chest radiography and echocardiography. All the patients were followed up for 1. 5 - 12 ( mean 6. 4 ± 0. 7) years. Results Systolic pulmonary arterial pressure (sPAP) of 60 - 108 (88. 7 ± 11. 7) mmHg and mean pulmonary artery pressure ( mPAP) of 29. 3 - 60 (51. 0 ± 8. 1) mmHg were measured by cardiac catheterization before ASD closure. Qp/ Qs was 1. 50 - 2. 44 (1. 8 ± 0. 31) and the pulmonary vascular resistance was 3. 1 - 9. 7 (5. 6 ± 1. 5) wood units (wu) . Immediately after the implantation of fenestrated occluders, sPAP decreased to 56 - 99 (70 ± 11. 5) mmHg and mPAP to 27 - 51. 7 (41. 1 ± 7. 1) mmHg. On the 3 d, 3 m and 6 m follow-up exam, RVEDd decreased ( P ﹤ 0. 05), while LVEDd, LVEDV and LVEF increased significantly (P ﹤ 0. 05) . sPAP decreased significantly after transcatheter closure at 3 m and 6 m as compared to pre-closure levels (both P ﹤ 0. 05) . The mean sPAP in long term follow up was (60. 2 ± 13. 3) mmHg which had significant decrease compared to pre-closure level ( P ﹤ 0. 01), but no significant difference found when compared to 6 m follow up (P ﹥ 0. 05). Conclusions ASD closure with fenestrated ASO is a satisfactory approach for ASD with severe PAH.
9.Protection of curcumin against tumor necrotic factor-alpha-mediated inflammatory injury of vascular endothelial cells
Yun ZHAO ; Xiumin HAN ; Ming ZHAO ; Yinghui SUN ; Xianyang ZHU ; Duanzhen ZHANG
Chinese Journal of Tissue Engineering Research 2014;(38):6165-6171
BACKGROUND:Previous studies have shown that, curcumin plays a crucial role on the inflammation in cells caused by oxidative stress.
OBJECTIVE:To elucidate the biological effect and mechanism of curcumin in the pathological inflammation reaction in vascular endothelial cells.
METHODHuman vascular endothelial cells were taken as the cellmodels. Tumor necrosis factor (10μg/L) treatment was used to induce the inflammation of cells. Curcumin (0, 50, 100μg/L) treatment for 24 hours was used to intervene the cells. The intercellular hyperpermeability of the vascular endothelial cellmonolayers was examined by HRP-conjugated bovine serum albumin, and intercellular filamentous actin stress fiber formation was examined by rhodamin-phal oidin staining. ELISA assay was used to detect the secretion of interleukin-1βin vascular endothelial cells. Immunoflurensece staining was applied to investigate the expression and translocalization of nuclear factor-κB. Western blot analysis reflected the expression of NRLP3 and caspase-1.
RESULTS AND CONCLUSION:HRP-bovine serum albumin detection results showed that, curcumin inhibited the intercellular hyperpermeability of the vascular endothelial cellmonolayers and the formation of robust intercellular filamentous actin in a dose-dependent manner. ELISA assay showed that curcumin protected vascular endothelial cells against tumor necrotic factor-α-induced interleukin-1βsecretion in a dose-dependent manner. Meanwhile, the nuclear factor-κB expression was increased and the translocation of nuclear factor-κB into the nuclei was obviously seen in vascular endothelial cells induced by tumor necrosis factor-α, but the translocation was not changed in 100μg/L curcumin-treated cells. Furthermore, western blot analysis revealed that the expression of NRLP3 and caspase-1 were inhibited in curcumin-treated cells. Curcumin can inhibit tumor necrosis factor-α-induced activation of inflammasome and secretion of interleukin-1βin vascular endothelial cells by down-regulating the expression of nuclear factor-κB, thus prevent pathological inflammatory injury in cells.
10.Clinical efficacy and long-term outcome of transcatheter occlusion for rupture of valsalva aneurysm ruptured into right atrium
Jiawang XIAO ; Xianyang ZHU ; Qiguang WANG ; Duanzhen ZHANG ; Chunsheng CUI ; Po ZHANG ; Lili MENG ; Huoyuan CHEN ; Ming ZHAO
Chinese Journal of Interventional Cardiology 2017;25(3):127-132
Objective To evaluate the clinical safety, efficacy and long-term outcome of transcatheter occlusion for ruptured aortic sinus of valsalva aneurysm (RASA) into the right atrium.Methods Between January 2006 and April 2013, fifteen patients [11 males and 4 females,aged from 21 to 48 years with an mean age of (35.50±8.79) years] with RASA ruptured into the right atrium were enrolled in this study.Domestic made patent ductus arteriosus (applied in six patients) or small waist double-disk ventricular septal defect (applied in nine patients) occluders were used for transcatheter closure.All the patients were followed up for any change in cardiac rhythm,and residual shunt,occluders morphology and possible valve regurgitation by echocardiography.Results All RASA were confirmed by aortography,including eleven cases with rupture of right coronary sinus of valsalva and four cases with rupture of the noncoronary sinus of valsalva shunting into the right atrium.NYHA function class was(2.56±0.63)before the occlusion.Cardiac catheterization showed mean pulmonary arterial pressure and Qp/Qs ratio were (25.38±8.21)mmHg (1 mmHg=0.133 kPa) and 1.34-2.81(1.93±0.39), respectively.Aortic angiography showed that the RSA was 4-10(6.42±1.92)mm at its narrowest end.There was no serious complication during the operation and all the patients had successful transcatheter closure without residual shunt.After transcatheter RASA occlusion, mean pulmonary artery pressure decreased to (16.1±5.3) mmHg (P<0.05).The diameter of right atrium,right ventricle, left atrium and pulmonary artery diameter and left ventricular end-diastolic dimension all showed significant decrease (P<0.01).All patients were followed up for 35-132(78.6±28.57)months.All patients presented with a NYHA function class Ⅰ to Ⅱ cardiac function in their last follow up which was significantly improved compare to pre-occlusion level (P<0.01).There were no infective endocarditis,device displacement and embolism,serious aortic regurgitation,myocardial ischemia,serious arrhythmia or death in any of the patients during follow up.Conclusions Transcatheter closure of Valsalva aneurysm ruptured into right atrium with the domestic made patient ductus arteriosus and small-waist ventricular septal defect occluder is safe and effective with a good long term prognosis.