Explore the vast range of titles available.

Vascular calcification is associated with cardiovascular disease as a complication of hypertension, hyperlipidemia, diabetes mellitus, and chronic kidney disease. Vitamin K2 (VK2) delays vascular calcification by an unclear mechanism. Moreover, apoptosis modulates vascular smooth muscle cell (VSMC) calcification. This paper aimed to study VK2-modified VSMC calcification and survival cell signaling mediated by growth arrest-specific gene 6 (Gas6) and its tyrosine kinase receptor Axl. Primary-cultured VSMCs were dose-dependently treated with VK2 in the presence of calcification medium for 8 days, or pre-treated for 1 h with/without the Axl inhibitor R428 (2 μmol/L) or the caspase inhibitor Z-VAD-fmk (20 μmol/L) followed by treatment with VK2 (10 μmol/L) or rmGas6 (200 nmol/L) in calcification medium for 8 days. Calcium deposition was determined by the o -cresolphthalein complexone assay and Alizarin Red S staining. Apoptosis was determined by TUNEL and flow cytometry using Annexin V-FITC and propidium iodide staining. Western blotting detected the expressions of Axl, Gas6, p-Akt, Akt, and Bcl2. VK2 significantly inhibited CaCl 2 - and β-sodium glycerophosphate (β-GP)-induced VSMC calcification and apoptosis, which was dependent on restored Gas6 expression and activated downstream signaling by Axl, p-Akt, and Bcl2. Z-VAD-fmk significantly inhibited CaCl 2 - and β-GP-induced VSMC calcification and apoptosis. Augmented recombinant mouse Gas6 protein (rmGas6) expression significantly reduced VSMC calcification and apoptosis. Furthermore, the Gas6/Axl interaction was inhibited by R428, which abolished the preventive effect of VK2 on CaCl 2 - and β-GP-induced apoptosis and calcification. These results suggest that Gas6 is critical in VK2-mediated functions that attenuate CaCl 2 - and β-GP-induced VSMC calcification by blocking apoptosis.

Bone marrow mesenchymal stem cells (BMMSCs) are ideal seed cells for tissue engineering and regenerative medicine. Many studies have shown that 5-azacytidine (5-aza) can induce BMMSCs to differentiate into cardiomyogenic cells, but some issues still remain to be resolved. In this study, we investigated the effects of angiotensin II (Ang II) on the proliferation and differentiation of BMMSCs induced by 5-aza in vitro. BMMSCs were isolated from the bone marrow of Sprague-Dawley rats by density gradient centrifugation. The third-passage cells were divided into four groups: the Ang II group (0. 1 μmol/l) (group A), the 5-aza group (10 μmol/l) (group B), the Ang II combined with 5-aza group (0.1 and 10 μmol/l) (group C), and the untreated group as control. After 24 h of induction, the medium was changed to the complete culture medium without any inductor, and the cells were cultured for 3 weeks. Morphological changes were observed under a phase contrast microscope. The effect of Ang II and 5-aza on BMMSC proliferation was evaluated by the methyl thiazolyl tetrazolium (MTT) assay. Cardiomyogenic cells were identified through immunofluorescence staining, and the induction ratio was examined by flow cytometry. The level of cardiac troponin I (cTnI) was examined by western blotting, and the ultrastructures of the induced cells were viewed with a transmission electron microscope. The MTT assay showed that the cell proliferation in group C outweighed that in either group A or group B, but no significant difference existed between group A and group B. The expression of specific proteins, namely, cTnI and sarcomeric α-actin in induced BMMSCs was verified as positive. Flow cytometry showed that the induction ratio in group C was higher than that in group A or group B. The protein levels of cTnI in groups A, B, and C were significantly higher than those in the control group. Transmission electron microscopy showed that the induced cells had myofilaments, z line-like substances, desmosomes, and gap junctions. Angiotensin II and 5-azacytidine can promote the proliferation and differentiation of BMMSCs into cardiomyocyte-like cells.

Background To explore the feasibility of constructing engineered myocardial tissues (EMTs) in vivo , using polylactic acid -co-glycolic acid (PLGA) for scaffold and cardiomyocyte-like cells derived from bone marrow mesenchymal stem cells (BMMSCs) for seeded cells. Methods BMMSCs were isolated from femur and tibia of Sprague-Dawley (SD) rats by density-gradient centrifugation. The third passage cells were treated with 10 μmol/L 5-azacytidine (5-aza) and 0.1 μmol/L angiotensin II (Ang II) for 24 h, followed by culturing in complete medium for 3 weeks to differentiated into cardiomyocyte-like cells. The cardiomyocyte-like cells were seeded into PLGA scaffolds to form the grafts. The grafts were cultured in the incubator for three days and then implanted into the peritoneal cavity of SD rats. Four weeks later, routine hematoxylin-eosin (HE) staining, immunohistochemical staining for myocardium-specific cardiac troponin I (cTnI), scanning electron microscopy and transmission electron microscopy were used to analyze the morphology and microconstruction of the EMTs in host rats. Results HE staining showed that the cardiomyocyte-like cells distributed equally in the PLGA scaffold, and the nuclei arranged in the spindle shape. Immunohistochemical staining revealed that majority of engrafted cells in the PLGA -Cardiomyocyte-like cells group were positive for cTnI. Scanning electron microscopy showed that the inoculated cells well attached to PLGA and grew in 3 dimensions in construct. Transmission electron microscopy showed that the EMTs contained well arranged myofilaments paralleled to the longitudinal cell axis, the cells were rich in endoplasmic reticulum and mitochondria, while desmosomes, gap junction and Z line-like substances were also can be observed as well within the engrafted cells. Conclusion We have developed an in vivo method to construct engineered myocardial tissue. The in vivo microenvironment helped engrafted cells/tissue survive and share similarities with the native heart tissue.

Abstract Aims The optimal dosing strategies for blocking the renin-angiotensin-aldosterone system in idiopathic dilated cardiomyopathy (IDCM) are poorly known. We sought to determine the long-term efficacy and safety of supramaximal titration of benazepril and valsartan in patients with IDCM. Methods and results 480 patients with IDCM in New York Heart Association functional class II–IV and with left ventricular ejection fraction ≤35% were randomly assigned to extended-release metoprolol (mean 152 mg/day, range 23.75–190), low-dose benazepril (20 mg/day), low-dose valsartan (160 mg/day), high-dose benazepril (mean 69 mg/day, range 40–80), and high-dose valsartan (mean 526 mg/day, range 320–640). After a median follow-up of 4.2 years, high-dose benazepril and valsartan, compared with their respective low dosages, resulted in 41% and 52% risk reduction in the primary endpoint of all-cause death or admission for heart failure (P = 0.042 and 0.002), promoted functional improvement, and reversed remodelling as assessed by New York Heart Association classes, quality-of-life scores, and echocardiographic recording of left ventricular ejection fraction, left ventricular end-diastolic volume, mitral regurgitation, and wall motion score index. Compared with metoprolol, high-dose valsartan reduced risk for the primary endpoint by 46% (P = 0.006), whereas high-dose benazepril and both low-dose groups showed no significant difference. Major adverse events involved hypotension and renal impairment but were largely tolerated. Conclusions Supramaximal doses of benazepril and valsartan were well tolerated and produced extra benefit than their low dosages in clinical outcome and cardiac reverse remodelling in patients with IDCM and modest-severe heart failure. ClinicalTrials.gov identifier: NCT01917149.

Objective: It was the aim of this study to investigate the impact of pulsed magnetic field (PMF) on ischemic myocardium, though it has been reported that PMF treatment is a safe and effective method to facilitate bone and cutaneous wound healing. Methods: In this report, we describe a study in which 10 Hz 4 mT PMF and 15 Hz 6 mT PMF was used to treat rats with myocardial infarction (MI). Results: After 28 days of treatment, the rats treated with 15 Hz 6 mT PMF exhibited decreased left ventricular end-diastolic pressure and accelerated maximum dp/dt of left ventricular pressure when compared with the untreated MI and the MI + 10 Hz 4 mT groups. Additionally, capillary density was increased and infarction area size was decreased in the MI + 15 Hz 6 mT group. Furthermore, the plasma vascular endothelial growth factor concentration and the protein expression of vascular endothelial growth factor receptor 2 in myocardial tissue were increased in rats of the MI + 15 Hz 6 mT group. Conclusion: This study shows that 15 Hz 6 mT PMF promotes myocardial angiogenesis and improves cardiac function after MI in rats. This suggests that there is a potential use for some PMF signal strengths in ischemic myocardial disease.

Organic‐encapsulated Fe3O4 magnetic microspheres (MMS) were synthesized and used to prepare PLLA (poly (L‐lactic acid))/MMS composites. The effects of organic encapsulation on the mechanical, thermal, and magnetic properties of the composites were investigated. When compared with the PLLA/Fe3O4 composite, the elongation ratio of the PLLA/MMS composite improved significantly (by nearly 300%). Scanning electron microscope (SEM) images of the fracture morphology revealed an interesting “silking” phenomenon within the PLLA/MMS composite, which explains the greatly improved toughness. The decreased crystallinity and increased thermal stability of the PLLA/MMS composite suggest the existence of strong interacting forces between the PLLA molecules and the organic layer of the MMS particles, thereby limiting the mobility of the macromolecular chains. A study of the composites' magnetic properties indicated that the saturation magnetization was determined by the relative Fe3O4 content in the matrix, but not the types of the filling particles. POLYM. ENG. SCI., 2009. © 2009 Society of Plastics Engineers

P53 is shown recently to play an important role in the proliferation and differentiation of bone marrow mesenchymal stem cells (BMMSCs). In this study, by inhibiting p53-p21 pathway with p53 inhibitor (p-fifty three inhibitor-alpha, PFT-α), we investigated the resulting effects on the differentiation of rat BMMSCs into cardiomyocyte-like cells. BMMSCs were isolated from bone marrow of SD rats by density gradient centrifugation. The fourth passage cells were divided into four groups: control group, PFT-α group, 5-AZA group, and PFT-α + 5-AZA group. The purified BMMSCs were identified by surface antigens and the proliferation and apoptosis of BMMSCs were examined by MTT and flow cytometry analysis. The expression of cTnI and CX-43 in BMMSCs after induction was detected by immunofluorescence and that of cTnI, p53, and p21 was detected by western blot. Our results demonstrated that PFT-α at 20 μmol/l significantly reduced the apoptosis and promoted the proliferation of BMMSCs, and induced BMMSCs to differentiate into cardiomyocyte-like cells. In conclusion, these data open up new possibility of modulating p53-p21 pathway for directed differentiation of BMMSCs into cardiomyocytes, which will be valuable for cardiovascular regenerative medicine.

Insulin has been shown to possess significant anti-apoptotic effect in myocardial ischemia/reperfusion (MI/R). However, the contribution by this protection of insulin to the prolonged cardiac function in rats subjected to ischemia remains unclear. The present study attempted to test whether early insulin treatment influences adverse prolonged post-ischemic cardiac structural and functional changes. Adult male rats were subjected to left anterior descending coronary artery occlusion and were randomized to receive one of the following treatments: saline (4 ml/kg/h i.v. injection beginning 10 min before the ischemia and continuing for 2 h), insulin (60 U/l, i.v. injection following the same routine, and hypodermic injection of insulin (0.5 U/ml, 1 ml/kg/d) for 3 days after the ischemia surgery) or insulin plus wortmannin (15 μg/kg i.v. injection 15 min before each insulin administration). Treatment with insulin significantly reduced infarct size, decreased plasma creatine kinase and lactate dehydrogenase activities, decreased apoptosis index and caspase-3 activity (all P < 0.01 vs. saline), and improved cardiac function 24 h after ischemia. Importantly, at the end of 4 weeks after the ischemia surgery, MI rats receiving insulin treatment showed smaller left ventricle (LV) cavity and thicker systolic interventricular septum, and increased cardiac ejection fraction and LV fractional shortening (all P < 0.05 vs. saline). Inhibition of insulin signaling with wortmannin not only blocked insulin's anti-apoptotic effect, but also almost completely abolished effects of insulin on cardiac structure and function. These data indicate that inhibition of apoptosis by early insulin treatment alleviates chronic adverse changes in post-ischemic cardiac structure and function.

Objectives To evaluate the initial and long-term clinical outcomes of patients with unprotected left main (ULM) stenosis undergoing percutaneous coronary intervention (PCI) with drug eluting stents (DES) at XiJing Hospital Centre in real world patient population. Methods After excluding acute ST-segment elevation myocardial infarction and bailout stenting, 798 patients treated for ULM disease with DES from January 2003 to December 2011 at XiJing Hospital were enrolled. The clinical outcomes of ULM treated with DES were evaluated by major adverse cardiac events (MACE) and stent thrombosis (ST) during in-hospital period and after long-term follow-up respectively. MACE was defined as cardiac death, non-fatal myocardial infarction (MI) and clinically driven target lesion revascularisation (TLR). ST was evaluated in accordance with the Academic Research Consortium (ARC) definitions. Results The mean age of study population was 62±10 years, 649 (81%) patients were male, 199 (25%) patients were diabetic, and the mean ejection fraction was 54%±11%. 71 (9%) patients had an ostial and 27 (3%) had a shaft lesion (nondistal subgroup), 700 (88%) patients had a bifurcation lesion (distal subgroup). In distal subgroup, 416 (59%) patients were treated with 1 stent (1-stent subgroup) and 284 (41%) were treated with 2 stent (2-stent subgroup). Among 2-stent subgroup, 74 (11%) patients were treated with crush (crush subgroup), 86 (12%) were treated with culotte (culotte subgroup), 43 (6%) were treated with kissing (kissing subgroup) and 81 (12%) were treated with T stenting (T subgroup). Angiographic and clinical successes of PCI were obtained in all patients. During the in-hospital period, MACE occurred in 7 (0.8%) patients including 5 (0.6%) cardiac deaths and 2 (0.2%) MIs. one patient had definite (died) and four patients had probable stent thrombosis (1 had a MI and 3 died). During the long-term follow-up duration of 27±20 months, MACE occurred in 176 (22%) patients including 25 (3%) cardiac deaths, 16 (2%) MIs and 135 (17%) TLRs. six patients had probable (died) and 12 patients had possible stent thrombosis (2 had MI and 10 died). There were no significant differences in in-hospital MACE rates between nondistal and distal subgroup, between 1-stent and 2-stent subgroup and among different 2-stent technique subgroups. After long-term follow-up, the TLR rate was significantly higher in distal subgroup than in nondistal subgroup (18% vs 9%, p<0.05), the MACE rate was significantly higher in 2-stent subgroup than in 1-stent subgroup (28% vs 20%, p<0.05), and the different 2-stent technique subgroups showed similar long-term outcomes. The total stent thrombosis rates were also no significant differences between nondistal and distal subgroup, between 1-stent and 2-stent subgroup and among different 2-stent technique subgroups. Conclusions Treatment of ULM with DES is feasible and safe with good in-hospital and acceptable long-term clinical results. Compared with ostial and shaft lesion, distal bifurcation lesion is associated with a worse long-term TLR rate. 1-stent technique had a better long-term MACE rate than 2-stent technique when distal bifurcation lesion was treated, whereas different 2-stent techniques had similar clinical outcomes.

Organic-encapsulated Fe^sub 3^O^sub 4^ magnetic microspheres (MMS) were synthesized and used to prepare PLLA (poly (L-lactic acid))/MMS composites. The effects of organic encapsulation on the mechanical, thermal, and magnetic properties of the composites were investigated. When compared with the PLLA/Fe^sub 3^O^sub 4^ composite, the elongation ratio of the PLLA/MMS composite improved significantly (by nearly 300%). Scanning electron microscope (SEM) images of the fracture morphology revealed an interesting \"silking'' phenomenon within the PLLA/MMS composite, which explains the greatly improved toughness. The decreased crystallinity and increased thermal stability of the PLLA/MMS composite suggest the existence of strong interacting forces between the PLLA molecules and the organic layer of the MMS particles, thereby limiting the mobility of the macromolecular chains. A study of the composites' magnetic properties indicated that the saturation magnetization was determined by the relative Fe^sub 3^O^sub 4^ content in the matrix, but not the types of the filling particles. [PUBLICATION ABSTRACT]