Along with the coming of aged society, the prevalence of heart valvular disease is significantly increasing, and the use of bioprosthetic valves for treating patients with severe valve disease has increased over the last two decades. As a consequence, a growing number of patients with surgical bioprosthesis degeneration is predicted in the near future. In this setting, valve-in-valve (ViV) transcatheter aortic/mitral valve replacement (TAVR/TMVR) has emerged as an alternative to redo surgery. A deep knowledge of the mechanism and features of the failed bioprosthetic heart valve is pivotal to plan an adequate procedure. Multimodal imaging is fundamental in the diagnostic and pre-procedural phases. The immediate and mid-term clinical and hemodynamic results have demonstrated the safety and feasibility of ViV techniques, but the development of these techniques faces several specific challenges, such as coronary obstruction, potential post-procedural mismatch and leaflet thrombosis. This article reviews the current status and prospects of ViV-TAVR technology in the treatment for biological valve degeneration, and suggests that ViV-TAVR should be promoted and implemented in existing medical centers with good surgical aortic valve replacement experience, so as to provide better treatment for patients.
Objective To investigate the effects of 1, 25-( OH) 2D3 on the expression of matrix metalloprotease-9 ( MMP-9) and nuclear factor κB ( NF-κB) activity in a murine model of chronic asthma. Methods BALB/ c mice were sensitized and challenged with ovalbumin to establish chronic asthmatic model. The animals were randomly divided into a control group, an asthma group and a VD group. Lung sections from the mice were stained by HE and Masson’s trichrome, respectively. Morphometric analysis of the stained sections was performed using computerized image analysis system. Nuclear translocation of NF-κB p65 was examined using Western blot. The level of IκBαwas detected with real-time quantitative PCR ( RTPCR) and Western blot. In addition, the expression of MMP-9 in both activity and mRNA level was detected by gelatin zymograph and RT-PCR, respectively. Results Prominent airway remodeling developed in the asthma group, including the inflammatory cell infiltration, subepithelial collagen deposition and increased airway smooth muscle mass. In contrast, 1, 25-( OH) 2D3 attenuated these established structural changes of the airways. Stimulation with OVA induced a 7. 87-fold increase in the MMP-9 activity compared with that in the control group, and 1, 25-( OH) 2D3 treatment only induced a 3. 46-fold increase in the MMP-9 activity compared with that in the control group ( P lt;0. 05) . The mRNA level of MMP-9 in the VD group ( 3.16 ± 0.09) was decreased compared with the asthma group ( 5.74 ±0.13) ( P lt;0.05) , but itwas still higher than that in the control group ( 0.57 ±0.08) ( P lt;0.05) . 1, 25-( OH) 2D3 reduced the nuclear translocation of NF-κB p65 while up-regulated the IκBα level in lung tissue of chronic asthma. Conclusions 1, 25- ( OH) 2D3 can inhibit the NF-κB activity and down-regulate the expression of MMP-9 in lung tissue of chronic asthma, thus alleviating the established chronic asthma-induced airway remodeling.
Objective By observation of the diameter, progression rate, wall thickness, and the opening angle of the abnormal aortic of abdominal aortic aneurysm (AAA) in rats, to observe the effect of saturated hydrogen saline on residual strain of AAA rats, and to investigate its inhibition effect on AAA formation. Methods Twenty healthy male Sprague Dawley rats (weighing, 200-220 g) were randomly divided into 2 groups, which was made the AAA model by infiltration of the abdominal arota with 0.5 mol/L calcium chloride. Saturated hydrogen saline (5 mL/kg) or saline (5 mL/kg) was injected intraperitoneally in the experimental group or control group respectively, every day for 28 days. At 28 days, the diameter, progression rate, wall thickness, and opening angle of the abnormal aorta were mearsured. The aortic tissue was harvested for histological examination (HE staining and aldehyde-fuchsin staining). Results At 28 days after operation, the diameter of abnormal aorta in 2 groups were significantly higher than preoperative ones (P lt; 0.05), the progression rate in experimental group (65% ± 15%) was significantly lower than that in control group (128% ± 54%) (t=3.611, P=0.005). The opening angle and the wall thickness in experimental group were (88.78 ± 29.20)° and (0.14 ± 0.03) mm respectively, had significant differences when compared with the values in control group [(44.23 ± 28.52)° and (0.36 ± 0.05) mm respectively] (P lt; 0.01). The integrity and continuity of the aortic wall in experimental group were superior to that in the control group. Compared with the control group, the injury of elastic fiber in aortic wall and the infiltration of inflammation were all reduced. Conclusion Saturated hydrogen saline can maintain good mechanical properties and reduce dilatation of the aorta by increasing residual strain and reducing the remodeling of it.
ObjectiveTo review the role and mechanism of protein factors in bone remodeling, and provides theoretical basis for further elucidating the pathogenesis and clinical treatment of bone-related diseases. MethodsThe relevant research results at home and abroad in recent years were extensively consulted, analyzed, and summarized. ResultsBone remodeling is an important physiological process to maintain bone homeostasis. Protein, as an important stimulator in bone remodeling, regulates the balance between bone resorption and bone formation. ConclusionAt present, the research on the mechanism of protein in bone remodeling is insufficient. Therefore, it is necessary to further study the specific time, process, and interaction network of protein in bone remodeling, and to confirm its mechanism in bone remodeling, so as to reveal and treat the pathogenesis of bone-related diseases.
Abstract： Objective To investigate the effects of βreceptor blocker on intraventricular pressure gradient and left ventricle remodeling after valve replacement for critical aortic stenosis. Methods Fifty-six patients with critical aortic stenosis underwent aortic valve replacement surgery from January 2008 to January 2010 in the First Affiliated Hospital of Zhengzhou University. Thirtytwo of them who were followed up were selected to be enrolled in this study. The patients were divided into two groups under the same basis of clinical features. Twelve patients in the experimental group received oral βreceptor blocker (Metoprolol, 6.2525.00 mg once, twice daily). The rest 20 patients in the control group had no βreceptor blocker. The various indicators of ultrasound cardiogram (UCG) shortly after operation (within a week) and long after operation (6-24 months) were compared between the two groups. Results No death occurred in both groups, and chest distress, shortness of breath and other symptoms were obviously alleviated. Although left ventricular endsystolic dimension (LVESD) and left ventricular outflow tract dimension (LVOTD) of both groups increased 6-24 months after operation, compared with the early postoperative period, only the increase of LVOTD in the experimental group showed statistical difference (t=-47.937, P=0.001). In both groups, interventricular septum thickness (IVST), left ventricular posterior wall thickness (LVPWT), filament band velocity of left ventricular outflow tract (V), intraventricular pressure gradient (G) and left ventricular mass index (LVMI) of the later period after operation were significantly lower than those of the early postoperative period. All these indicators in the experimental group showed significant differences (t=7.781, P=0.001；t=5.749, P=0.001; t=2.637, P=0.023; t=7.167, P=0.001; t=100.061, P0.001), while only V, G， and LVMI showed statistical differences in the control group (t=4.051, P=0.001; t= 4.759, P= 0.001; t=-0.166,P=0.001). EF in the experimental group also indicated significant difference compared with early period after aortic valve replacement (t=-6.621, P=0.001). EF between two groups indicated no significant difference (t=-0.354,P=0.726). But differences between the two groups in LVEDD, IVS, G， and LVMI were all statistically significant in the later period after surgery (t=-2.494, P=0.018; t=-3.434, P=0.002;t=-2.171,P=0.038; t=-2.316, P=0.028). Conclusion β-receptor blocker is a safe and reliable drug for those patients who have undergone aortic valve replacement surgery for critical aortic stenosis, and can decrease significantly the residual intraventricular pressure gradient and accelerate left ventricular cardiac remodeling.
Objective To observe the effects of taurine on ventricular remodeling of rats with acute myocardial infarction (AMI) though the establishment of rat AMI model by ligating the left anterior descending coronary branch. Methods Sixty 8-week-old male Wistar rats were randomly divided into four groups: sham group, AMI group, small-dose and high-dose taurine group, with 15 rats in each. Rats in the AMI group and taurine groups received ligation of the anterior descending coronary branch to establish an animal model of AMI. Meanwhile, rats in the sham group were subjected to sham coronary ligature. From the next day of the operation, rats in the taurine groups were dosed orally per day with taurine 300 mg/kg or 400 mg/kg for 8 weeks, respectively. Echocardiographic images were acquired before and 8 weeks after the operation, to get the indexes such as left ventricular end systolic diameter (LVIDs), left ventricular end diastolic diameter (LVIDd), left ventricular posterior wall end diastolic thickness (LVPWd), left ventricular ejection fraction (LVEF), fractional shortening (FS), mitral inflow velocity E (E), mitral inflow velocity A (A), and E/A ratio, and all the measurements above were expressed as the average of 6 consecutive cardiac cycles. After the animals were executed, cardiac mass and left ventricular mass were measured, and cardiac mass index (CMI) and left ventricular mass index (LVMI) were calculated. Brain natriuretic peptide (BNP) in all groups were measured by enzyme-linked immunosorbent assay before and 8 weeks after the operation. Results In comparison with the AMI group, CMI, LVMI, LVIDd and LVIDs of the small-dose and high-dose taurine groups were lower, and LVPWd, LVEF, FS and E/A were higher (P<0.05). Plasma BNP level in the AMI group and two taurine-treated groups were higher than that in the sham group, and it was the highest in the AMI group (P<0.05). Conclusion Taurine has a protective effect on ventricular remodeling in rats with AMI, and the protective effect is dose-dependent.
In order to identify whether the regeneration of costal cartilage is the basis of post-surgical repair of pectus excavatum and thoracic cage remodeling, 151 cases were followed up for 0.25 to 14 years. The main procedures in treatment were 3 steps: To curve the mental strut as a bow, to repair the perichondrium as a tube, and to persist in post-operative therapy. The results showed that regeneration of the costal cartilages appeared 3 months postoperatively in the cases treated by this method. It was concluded that a satisfactory thoracic cage could be remodeled by improving the technique of repairing pectus excavatum and persisting in postoperative therapy according to the regeneration regularity.
Objective To investigate the effects of tissue inhibitor-3 of matrix metalloproteinases(TIMP-3) genetransfected vascular smooth muscle cells(VSMCs) transplantation on heart structure after acute myocardial infarction (AMI) in rats and to explore the potential mechanisms. Methods Sixty-one female Wistar rats were produced AMI models by ligating the descending left coronary artery. Fifty-four rats were survived and divided into 3 groups randomly(n=18): 0.5 ml PBS containing 1×106 TIMP-3 gene-transfected VSMCs(group A), 1×106 VSMCs(group B) or 0.5 ml PBS without cell(group C) were injected into the ischemic myocardium immediately. Ischemic myocardium samples were harvested at 1 weekafter operation. The heart structure was observed through the tissue morphologic examination. The activity of TIMP-3 gene-transfected VSMCs were measured by immunohistochemical method. Proteins of TIMP-3 and matrix metalloproteinase 9(MMP-9) were determined by Western blot. Results VSMCs were cultivated and had a high purity(98%). TIMP-3 gene was transfected into VSMCs successfully. One week after operation in groups A, B and C, the average percentage of infarction myocardium size 〖KG6〗and left ventricle free wal area were 28.73%±1.56%, 39.63%±1.84% and 46.32%±2.16% separately.Group A was significantly lower than groups B and C(P＜0.01), group B was significantly lower than group C(P＜0.01). In groups A, B and C the averageleft ventricle volume indexes were 5.27±0.21 mm3／g, 6.69±0.34 mm3／g and 9.67±0.88 mm3／g respectively. Group A was significantly smaller than groups B and C(P＜0.01), group B was significantly smaller than group C(P＜0.01). The immunohistochemical observation confirmed that the implanted VSMCs and TIMP-3 gene were survival in ischemic area. The protein content of TIMP-3 in ischemicmyocardium was significantly higher in group A (300 704.8±3 692.8) than in groups B and C(195 548.8±3 014.2，177 991.1±2 502.1)(P＜0.01), the protein content of MMP-9 in ischemic myocardium was significantly lower in group A(594 827.4±5 708.5) than in groups B and C(921 461.4±8 887.4，1 044 445.0±8 788.6)(P＜0.01). Conclusion Implanted TIMP3 gene transfected VSMCs in ischemic myocardium can conspicuously reduce the myocardium remodeling after AMI.
Objective To evaluate the effect of smooth muscle cell transplantation on myocardial interstitial reconstruction shortly after myocardial infarction. Methods A total of 48 female Wister rats were randomly divided into two groups with the random number table, the control group (n=24) and the smooth muscle cell transplantation group (n=24). The left coronary artery was ligated to set up the myocardial infarction animal model. An amount of 05 ml phosphate buffered saline(PBS) containing 1×106 smooth muscle cells or 0.5 ml PBS without cells was injected into the injured myocardium immediately. By immunoblot and reverse transcriptionolymerase china reaction (RT-PCR), we observed the amount of protein and mRNA of matrix metalloproteinase2(MMP-2), matrix metalloproteinase-9(MMP-9) and tissue inhibitor of metalloprotease-3 (TIMP-3) in the myocardium of the rats. Results The transplanted smooth muscle cells survived well. Compared with the control group, myocardial TIMP3 mRNA (1.06±0.22 vs. 0.81±0.19, t=－2.358, P=0.033) and protein content (3.33±0.53 vs. 1.63±0.47, t=－6.802, Plt;0.001) were significantly increased in the transplantation group. Myocardial MMP-2, MMP-9 mRNA (0.49±0.12 vs. 1.16±0.18, t=8.453, Plt;0.001; 0.45±0.12 vs. 0.80±0.11, t=5.884, Plt;0.001) and protein content (3.98±1.08 vs. 6.05±0.91, t=4.139, P=0.001; 0.39±0.14 vs. 0.57±0.17, t=2.409, P=0.031) [CM(1585mm]were significantly reduced in the transplantation group compared with the control group. Conclusion transplanted smooth muscle cells can survive well in the infarction myocardium and can increase the amount of myocardial TIMP-3 mRNA and protein content and reduce myocardial MMP-2, MMP-9 mRNA and protein content, which is an effective way to prevent harmful cardiac remodeling.
ObjectiveTo investigate the expression of extracellular signalregulated kinase (ERK) and p38 mitogenactivated protein kinase （p38 MAPK） in autogenous vein grafts during vascular remodeling.MethodsAn autogenous vein graft model was established by transplanting the right jugular vein to infrarenal abdominal aorta in 80 Wistar rats. Vein graft samples were harvested 6 hours, 24 hours, 3 days, 7 days, 2 weeks, 4 weeks, 6 weeks and 8 weeks after surgery. Gene expression of ERK and p38 MAPK was measured by reverse transcriptionPCR. Western blot was used to detect the expression of protein products and phosphorylation protein products of ERK and p38 MAPK. Apoptosis of vascular smooth muscle cells (VSMCs) was determined by TUNEL. Proliferating cell nuclear antigen(PCNA) of VSMCs also was studied.ResultsThe expression of ERK1 mRNA and p38 MAPK mRNA increased considerably after surgery. ERK1 mRNA reached the peak on the 7th day 〔（33.2±14.2）%, P＜0.01〕, but p38 MAPK mRNA reached the peak on the second week after surgery 〔(58.8±26.2）%, P＜0.01〕. The expression of ERK1/2 detected by western blot reached the peak during 1 to 2 weeks and decreased gradually to normal level 6 weeks after surgery. The expression of p38 MAPK reached the peak during 2 to 4 weeks and decreased to 1/4 to 1/2fold 8 weeks after surgery. There was a positive relationship between ERK1 and PCNA(r=0.759 6，P＜0.01) and a positive relationship between p38 MAPK and apoptosis(r=0.892 2，P＜0.01). ConclusionActivation of MAPK system exists in autogenous vein grafts and it may become a new target for the therapy of stenosis after vein grafts.