This study aimed to investigate the effects and potential mechanisms of Chikusetsusaponin V (CsV) on endothelial nitric oxide synthase (eNOS) and vascular endothelial cell functions. Different concentrations of CsV were added to animal models, bovine aorta endothelial cells (BAECs) and human umbilical vein endothelial cells (HUVECs) cultured in vitro. qPCR, Western blotting (WB), and B ultrasound were performed to explore the effects of CsV on mouse endothelial cell functions, vascular stiffness and cellular eNOS mRNA, protein expression and NO release. Bioinformatics analysis, network pharmacology, molecular docking and protein mass spectrometry analysis were conducted to jointly predict the upstream transcription factors of eNOS. Furthermore, pulldown and ChIP and dual luciferase assays were employed for subsequent verification. At the presence or absence of CsV stimulation, either overexpression or knockdown of purine rich element binding protein A (PURA) was conducted, and PCR assay was employed to detect PURA and eNOS mRNA expressions, Western blot was used to detect PURA and eNOS protein expressions, cell NO release and serum NO levels. Tube formation experiment was conducted to detect the tube forming capability of HUVECs cells. The animal vasodilation function test detected the vasodilation functions. Ultrasonic detection was performed to determine the mouse aortic arch pulse wave velocity to identify aortic stiffness. CsV stimulus on bovine aortic cells revealed that CsV could upregulate eNOS protein levels in vascular endothelial cells in a concentration and time dependent manner. The expression levels of eNOS mRNA and phosphorylation sites Ser1177, Ser633 and Thr495 increased significantly after CsV stimulation. Meanwhile, CsV could also enhance the tube forming capability of HUVECs cells. Following the mice were gavaged using CsV, the eNOS protein level of mouse aortic endothelial cells was upregulated in a concentration- and time-dependent manner, and serum NO release and vasodilation ability were simultaneously elevated whereas arterial stiffness was alleviated. The pulldown, ChIP and dual luciferase assays demonstrated that PURA could bind to the eNOS promoter and facilitate the transcription of eNOS. Under the conditions of presence or absence of CsV stimulation, overexpression or knockdown of PURA indicated that the effect of CsV on vascular endothelial function and eNOS was weakened following PURA gene silence, whereas overexpression of PURA gene could enhance the effect of CsV upregulating eNOS expression. CsV could promote NO release from endothelial cells by upregulating the expression of PURA/eNOS pathway, improve endothelial cell functions, enhance vasodilation capability, and alleviate vessel stiffness. The present study plays a role in offering a theoretical basis for the development and application of CsV in vascular function improvement, and it also provides a more comprehensive understanding of the pharmacodynamics of CsV.
Sung Kiick;Park Kay-Hyun;Lee Young Tak;Jun Tae-Gook;Yang Ji-Hyuk;Kim Su Wan;Kim Jin Sun;Cho Sung Woo;Kim Si Wook;Choi Jin Ho;Park Pyo Won
Journal of Chest Surgery
/
v.38
no.7
s.252
/
pp.483-488
/
2005
Aortic valve-sparing procedures could reduce valve-related morbidity, but may increase operative risks; therefore, these procedures could not be performed routinely. We attempted to find out the early results while focusing on the operative risks associated with these procedures in our hospital. Material and Method: From May 1996 to July 2003, 26 patients underwent these procedures including 15 patients with Marfan syndrome and 1 patient with Behcet disease. There were 17 men and 9 women with mean age of $37.9\pm19.2$ years (range: 6 months-74 years). Ten patients had ascending aortic dissection, 18 patients had more than moderate degree of aortic valve insufficiency (AI). Two types of valve-sparing procedures were performed: valve reimplantation in 14 and root remodeling in 12 patients. Associated procedures were performed as follows: aortic valve plasty in 6, mitral valve plasty in 5, hemi-arch replacement in 4, total arch replacement in 2, coronary artery bypass surgery in 1 and Maze procedure in 1 patient(s). Result: In four patients, valve-sparing procedures were converted to Bentall procedures during operation. Including these patients, there was no operative deaths, 3 patients underwent re-operation due to bleeding, 1 patient had permanent pacemaker. The median duration of ICU stay was 45.5 hours, the median duration of hospital stay was 10.5 days. In 22 patients excluding 4 converted patients, intraoperative transesophageal echocardiogram (TEE) showed less than mild degree of AI in all except one who had not received intra-operative TEE in the beginning and showed moderate degree of AI at discharge. The mean duration of follow-up was $21.2\pm27.4$ months. All patients were alive except one who died during other departmental surgery. In 3 patients, more than moderate degree of AI was recurred, but there were no reoperation. Conclusion: Aortic valve-sparing procedures could be performed relatively safely in selected patients who had annuloaortic ectasia.
Background: The aim of our study was to assess the extent of regression of left ventricular mass after aortic valve replacement in isolated aortic regurgitation. Material and Method: Retrospective analysis of echocardiographic data was collected preoperative and postoperative 1 year. There were 20 patients (12 males, 8 females, mean age $55.8{\pm}11.8$ years, mean body surface area $1.64{\pm}0.19m^2$) with aortic regurgitation from 2002 through 2007. We studied the change of left ventricular ejection fraction, ventricular septum and left ventricular posterior wall thickness, and left vemtricular muscle index (LVMI). The control group was age matched with normal echocardiographic study results. Patients with combined surgery or infective endocarditis were excluded. Result: Seven cases of tissue valves and thirteen cases of mechanical valve were used. The valve sizes were 21 mm (3 cases), 23 mm (13 cases) and 25 mm (4 cases). The postoperative ($125.5{\pm}42g/m^2$) LVMI has decreased than preoperative LVMI ($212.3{\pm}80g/m^2$, p=0.000) but higher than that of control group ($80.5{\pm}15.9g/m^2$, p=0.000). Postoperative septal wall (systolic/diastolic: $13.5{\pm}3.4mm/17.1{\pm}4.1mm$) and left ventricular posterior wall (systolic/diastolic: $12.9{\pm}3.4mm/16.7{\pm}3.4mm$) thickness were slightly decreased after the valve replacement but was not significantly different than preoperative levels. And postoperative interventricular septal wall and left ventricular posterior wall thickness (systolic/diastolic: $8.6{\pm}1.4mm/12.1{\pm}1.7mm$, systolic/diastolic: $8.4{\pm}1.4mm/13.2{\pm}1.9mm$) were higher than that of the control group (p<0.001). Conclusion: The significant regression of LVMI after aortic valve replacement developed at postoperative one year but the level was higher than control group. The main cause of decreased LVMI is decreased in left ventricular dimension.
Background: Side clamping of ascending aorta during proximal graft anastomosis in coronary bypassing surgery in-creases the risk of direct aortic injury as well as embolization of intimal atheroma. Heartstring proximal sealing system (Guidant Corporation, Santa Clara, Calif), developed to avoid aortic side clamping, may minimize risks of such complications. The aim of the current study is to compare the surgical outcomes of the two proximal anastomosis techniquesi.e., Heartstring system versus aortic side clamping in off pump coronary bypassing' surgery (OPCAB). Material and Method: From January 2003 to August 2008, 499 patients underwent OPCAB. Of them, proximal graft anastomosis was performed using Heartstring system in 182 patients (Group I) and conventional manual anastomosis in 317 patients (Group II). The two groups were compared for postoperative major complications and mortality. Result: Two groups showed similar characteristics in terms of preoperative demographic data, left ventricular ejection fraction, renal function and history of diabetes, hypertension and smoking. Although there was no inter-group difference in the history of cerebral ischemia (p=0.48), preoperative brain magnetic resonance angiography revealed greater incidence of severe carotid artery stenosis (>75% of lumen) in the Group I than in the. Group II (44.5% in the Group I and 30.0% in the Group II, p=0.003). There were no inter-group differences in postoperative mortality (p=0.40) and complications (p=0.47) including neurologic events (3 in the Group land 2 in the Group II, p=0.258). Whereas neurologic events all comprised transient ischemic attacks in the Group I, they comprised multiple embolic strokes in the Group II. One patient in the Group II experienced aortic dissection during proximal anastomosis which resulted in ascending aortic replacement. Conclusion: Although proximal anastomosis using Heartstring system did not show statistically significant benefit over aortic side clamping, the. absence of embolic stroke maybe a definite benefit which may be better defined through further studies over a larger cohort.
Background; The purpose of this study was to analyze the early and midterm results of Cabrol technique to assist in making future decisions on a more adequate technique for repairing aortic root diseases. Material and Method; From August 1993 to July 1999, we performed Cabrol technique in 18 patients ; 12 annuloaortic ectasia, 6 Stanford type A aortic dissection. Male and female ratio was 11;7, mean age was 46.9$\pm$12.3 years and mean follow up period was 22.5$\pm$21.5 months. We analysed the factors influencing postoperative complications and early mortality. The factors were old age(>60 years), high NYHA(>III), preoporative concomitant disease, urgency of operation, concomitant procedure, long pump preoperative concomitant disease, urgency of operation, concomitant procedure, long pump time(>200 minute), and hospital stay time (>30 days). Result; Operative mortality was 11.1%, late mortality was 11.1%, and overall mortality was 22.2%. The causes of operative death were a heart failure and an arrhythmia. The causes of late death were an acute myocardial infarction and an unknown etiology. Postoperative complications were bleeding, wound infection, toxic hepatitis, acute renal failure, and cerebral infarction. The factors influencing postoperative complications were hihg MYHA Fc(>III) (p=0.044), concomitant disease (p=0.044), long pump time(>200 minute)(p=0.015), and concomitant procedure(p=0.004). There were no significant factors influencing early mortality. Conclusion; The lower postoperative bleeding rate and no complication related to tension of anastomosis after Cabrol technique warrant its consideration in patients requiring aortic root replacement, especially without feasible mobilization of coronary arteries. However, to confirm the graft thrombosis, a more detailed study including periodic angiography will be required.
During 1986, 111 cases of open heart surgery were performed at Yeungnam University Hospital consisting 88 cases of congenital heart disease and 23 cases of acquired heart disease. Among 88 congenital heart disease, 72 were acyanotic group and 16 were cyanotic. Common congenital heart diseases were ventricular septal defect(51%), atrial septal defect(18%) and Tetralogy of Fallot(16%). Among 23 acquired heart disease, 22 cases were valvular heart disease and one was dissecting aortic aneurysm. Three cases of the postoperative death were present resulting 2.7% of surgical mortality rate.
This study reviewed useful aspects of the intraoperative transesophageal echocardiography among the patients in whom heart surgery were undertaken between January 1996 and July 1996 at St.Pauls hospital, Medical College of Catholic University, Seoul, Korea. During that period, 61 patients were operated on because of valvular heart disease(25 patients), coronary artery disease(22 patients), congenital heart disease(13 patients), and combined coronary artery disease and valvular heart disease(1 patient). Two patients(1 redo-VSD and 1 valvular heart diease) needed repeated aortic cross clamping and complementary procedures because of incomplete initial procedures. There was no incidence of air embolism. We could observe significant relationship of cardiac output monitoring methods either by thermodilution technique and transesophageal echocardiography by linear regression analysis(p<0.001). We tested myocardial response(percentage of systolic wall thickness, PSWT) with low dose dobutamine challenge to predict post-CABG myocardial perfusion. And the test showed statistically significant resp.onse(sensitivity 76%, specificity 94.7%, positive predictive value 95%, negative predictive value 75%). These results suggest that cardiac surgeon could draw more benefits by intraoperative transesophageal echocardiography.
Ha, Jung Min;Jin, Seo Yeon;Lee, Hye Sun;Shin, Hwa Kyoung;Lee, Dong Hyung;Song, Sang Heon;Kim, Chi Dae;Bae, Sun Sik
The Korean Journal of Physiology and Pharmacology
/
v.20
no.5
/
pp.533-538
/
2016
Angiogenesis plays an essential role in embryo development, tissue repair, inflammatory diseases, and tumor growth. In the present study, we showed that endothelial nitric oxide synthase (eNOS) regulates retinal angiogenesis. Mice that lack eNOS showed growth retardation, and retinal vessel development was significantly delayed. In addition, the number of tip cells and filopodia length were significantly reduced in mice lacking eNOS. Retinal endothelial cell proliferation was significantly blocked in mice lacking eNOS, and EMG-2-induced endothelial cell sprouting was significantly reduced in aortic vessels isolated from eNOS-deficient mice. Finally, pericyte recruitment to endothelial cells and vascular smooth muscle cell coverage to blood vessels were attenuated in mice lacking eNOS. Taken together, we suggest that the endothelial cell function and blood vessel maturation are regulated by eNOS during retinal angiogenesis.
Nitrotyrosine was found to be dependent on the severity of myxomatous mitral valve disease (MMVD). However, a correlation of serum nitrotyrosine concentration in dogs with MMVD and the progression of the disease has not been investigated. This study compared changes in serum nitrotyrosine concentration with the progression of MMVD. Nine client-owned dogs were recruited for the study. Dogs were classified by measuring the amount of regurgitation using echocardiography into mild, moderate, or severe MMVD groups. Serum nitrotyrosine concentration was measured by an enzyme-linked immunosorbent assay test. Serum nitrotyrosine concentration was significantly higher at 180 days than at 0 day (P < 0.05). However, serum nitrotyrosine concentration at 360 days was lower than that at 180 days (P < 0.05). Serum nitrotyrosine concentration at 540 days was lower than at 180 days (P < 0.05). There was no correlation between serum nitrotyrosine and left atrial to aortic root diameter ratio (LA/Ao ratio) (n = 33, $R^2=0.003$, P = 0.759). Also, there was no correlation between serum nitrotyrosine and vertebral heart score (VHS) (n = 33, $R^2=0.026$, P = 0.368) and left ventricular end-diastolic diameter, normalized for body weight by the formula (LVEDDN) (n = 33, $R^2=0.053$, P = 0.196). The results of the study suggest that the progression of MMVD is correlated with changes in serum nitrotyrosine concentration, which shows potential for use as a cardiac biomarker which can be used to analyze the progression of disease in MMVD.
Since the open heart surgery was performed, various kinds of problem concerning the extracorporeal circulation[EGG] have been known. The author investigated the changes of serum potassium ion before and after ECC among the 102 patients including 63 adults and 39 children who underwent open heart surgery from April 19S6 to February 1990 in Chung-Ang University Hospital. The mean values of potassium ion before and after ECC were analyzed according to the influencing factors such as priming solution, aortic cross clamping time, the underlying disease, the type of oxygenator and the amount of cardioplegic solution. The results were as follows: l. In the aspect of congenital and acquired heart disease groups, the mean values of serum potassium ion[Mean\ulcornerS.D.] before and after ECC revealed a significant change only in the acquired heart disease group[congenital; 3.87$\pm$0.48mEq /L vs. 4.05$\pm$0.73mEq /L, P>0.05, acquired: 4.40 $\pm$0.98mEq /L vs. 4.11$\pm$0.52mEq /L, P<0.05]. Between the two groups, the changes of the mean values of serum potassium ion before and after ECC were significant[P<0.05]. But all values were within normal limits. 2. In the aspect of the aortic cross clamping time[ACCT], in the groups of less or more than 120 minutes, the mean values of serum potassium ion before and after ECC revealed no significant change[less than 120 min; 3.97+-0.64mEq /L vs. 3.99+0.67mEq /L, P>0.05, more than 120 min; 4.34+0.82mEq /L vs. 4.27+0.62mEq /L, P>0.05], and The changes of mean values of serum potassium ion between the two groups were not significant[P>0.05]. 3. In both membrane and bubble oxygenator groups, the mean values of serum potassium ion before and after ECC did not reveal a significant difference respectively [membrane; 4.74 +1.40mEq /L vs. 4.28+0.3lmEq /L, P>0.05, bubble; 4.02 +0.60mEq /L vs. 4.05 L0.68mEq/L, P>0.05], and no differences between the membrane and bubble oxygenator groups[P >0.05]. 4. In the groups of membrane and bubble oxygenator in the cases of ACCT more than 120 minutes, the mean values of serum potassium ion before and after ECC did not reveal a significant difference respectively[membrane; 4.36$\pm$0.85mEq /L vs. 4.37$\pm$0.26mEq /L, P>0.05, bubble; 4.30 $\pm$0.80mEq/L vs. 4.23$\pm$0.67mEq/L, P>0.05], and no differences between the two groups[P>0.05]. 5. In spite of increased amount of cold potassium cardioplegic solution, the mean values of serum potassium ion before ECC were similar to those of serum potassium ion after ECC[less than 20ml /kg
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