Anlin Lv

Involvement of activated astrocyte and microglia of locus coeruleus in cardiac pain processing after acute cardiac injury

Abstract Objective: It is still not known whether the glial cell activation of locus coeruleus (LC) is involved in the neurophysiologic mechanism of the acute phase of heart disease. The aim of this study was to investigate whether the glial cell activation of LC responds to acute cardiac injury (ACI). Methods: In this study, ACI was established by intramyocardial injection of formalin. Afterward, we analysed c-Fos, OX42, GFAP and P2X4R expression levels in the LC of the rats by immunofluorescence staining or Western blot analysis. Results: There was no significant difference in the levels of these markers in the LC between the normal control and the sham-operated groups. Following ACI, up-regulation of GFAP, OX42 and P2X4R expression levels were observed in locus coeruleus of the rats. The peak expression time was at hour 24. P2X4R was colocalized with OX42 in activated microglias, but not with GFAP in activated astrocytes. Compared with the control group, the ACI group showed a high expression level of c-Fos at hour 1 with a peak expression level at hour 2. Conclusion: The results showed that LC glia cells, like neurons, could sensitively respond to cardiovascular nociception induced by ACI at different time points. Results of this study may provide insights into the role of glial activation in response to ACI and may represent a potential strategy for investigation of neurophysiologic mechanism of cardiac pain.

Insulin inhibits leukocyte-endothelium adherence via an Akt-NO-dependent mechanism in myocardial ischemia/reperfusion.

Clinical evidence indicates that intensive insulin therapy during critical illness protects the endothelium and contributes to prevention of organ failure and death but the mechanisms involved remain unclear. This study was designed to test the hypothesis that insulin inhibits adherence of polymorphonuclear leukocytes (PMNs) to endothelial cells in myocardial ischemia/reperfusion (MI/R) and to investigate the underlying mechanisms. Anesthetized rabbits were subjected to MI/R (45 min/4 h) and randomly received saline, glucose-insulin-potassium (GIK) or GK respectively (2 mL/kg/h, i.v.). In vitro study was performed on cultured endothelial cells subjected to simulated ischemia/reperfusion. In vivo treatment with GIK but not GK attenuated myocardial injury as evidenced by reduced plasma creatine kinase activity, myocardial apoptosis and infarct size in MI/R rabbits compared with the saline group. Interestingly, GIK but not GK significantly decreased coronary endothelial expression of P-selectin and intercellular adhesion molecule-1 (ICAM-1), inhibited adherence of PMNs to coronary endothelium (107.7+/-7.4 vs. 155.0+/-9.2 PMNs/mm(2) in saline group, n=8, P<0.01), and therefore decreased myocardial PMNs accumulation. In cultured endothelial cells subjected to simulated ischemia/reperfusion, insulin (10(-)(7) M) increased Akt activity and eNOS phosphorylation with subsequent NO production, and concurrently exerted an anti-adhesive effect as manifested by reduced endothelial P-selectin and ICAM-1 surface expression and PMNs adherence (13.7+/-1.3% vs. 22.2+/-1.9% in vehicle, n=9, P<0.01), all of which are abolished by the specific Akt inhibitor. Furthermore, inhibition of insulin-stimulated NO production using either the selective eNOS inhibitor cavtratin or the NOS inhibitor L-NAME blocked the anti-adhesive effect of insulin. These results demonstrate that insulin reduces endothelial P-selectin and ICAM-1 expression, and thus inhibits leukocyte-endothelium adherence in MI/R rabbit hearts. The anti-adhesive property by insulin may be mediated by the Akt-mediated and NO-dependent pathway.

Engineered myocardial tissues constructed in vivo using cardiomyocyte-like cells derived from bone marrow mesenchymal stem cells in rats

BackgroundTo 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.MethodsBMMSCs 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.ResultsHE 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.ConclusionWe 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.

Cyclic stretch upregulates SDF-1α/CXCR4 axis in human saphenous vein smooth muscle cells

Cyclic stretch (CS) mediates different cellular functions in vascular smooth muscle cells and involves in neointimal hyperplasia and subsequent atherosclerosis of vein grafts. Here, we investigated whether CS can modulate stromal cell-derived factor-1alpha (SDF-1alpha)/CXCR4 axis in human saphenous vein smooth muscle cells. We found CS induced the upregulation of SDF-1alpha and CXCR4 in human saphenous vein smooth muscle cells in vitro, which was dependent on PI3K/Akt/mTOR pathway. Furthermore, CS augmented human saphenous vein smooth muscle migration and focal adhesion kinase (FAK) activation by PI3K/Akt/mTOR pathway. Interestingly, the upregulation of SDF-1alpha/CXCR4 axis was instrumental in CS-induced saphenous vein smooth muscle cell migration and FAK activation, as showed by AMD3100, an inhibitor of SDF-1alpha/CXCR4 axis, partially but significantly blocked the CS-induced cellular effects. Thus, those data suggested SDF-1alpha/CXCR4 axis involves in CS-mediated cellular functions in human saphenous vein smooth muscle cells.

Pulsed Magnetic Field Induces Angiogenesis and Improves Cardiac Function of Surgically Induced Infarcted Myocardium in Sprague-Dawley Rats

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.

Biocompatible amphiphilic hyperbranched nanocapsules with a functional core: Synergistic encapsulation and asynchronous release properties towards multi-guest molecules

To achieve an encapsulation–release property towards multi-guest molecules, amphiphilic hyperbranched nanocapsules (AHN) consisting of a functional hyperbranched poly(β-cyclodextrin) [HBP(β-CD)] core and a methoxy polyethylene glycol shell was first constructed by click chemistry. The encapsulation–release capacity and corresponding mechanism of AHN towards multi-guest molecules were investigated by fluorescence and UV-vis spectroscopy. The results indicated that the encapsulation–release properties of AHN were pH dependent and can be applied to multi-guest systems. The multi-guest encapsulation capacity of AHN was derived from the synergistic encapsulation phenomenon of different guest molecules and the molecular recognition property of the HBP(β-CD) core. Compared with single-guest systems, AHN displays a sustained release characteristic accompanied by an “asynchronous release phenomenon” in multi-guest release systems. The release rate can also be effectively controlled because of the molecular recognition property of the HBP(β-CD) core. Both in vitro cell apoptosis and in vivo systematic toxicity assays confirmed that AHN possessed good biocompatibility.

Efficacy and safety of supramaximal titrated inhibition of renin-angiotensin-aldosterone system in idiopathic dilated cardiomyopathy

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.

Effect of chronic pretreatment of angiotensin-converting receptor blocker on no-reflow phenomenon in patients with acute myocardial infarction undergoing percutaneous coronary intervention.

AIMS Angiotensin receptor blockers (ARBs) exert favorable effects on the vascular system, which are not directly related to hypertension lowering function. The no-reflow phenomenon determines the prognosis in patients after acute myocardial infarction (AMI). Early ARB treatment has many beneficial effects on the prognosis after AMI. In this study, we tested the hypothesis that ARB treatment before admission would have beneficial effects on the development of the no-reflow phenomenon after infarction. METHODS We investigated 276 consecutive patients with AMI undergoing successful primary percutaneous coronary intervention (PCI). No-reflow was defined as thrombolysis in myocardial infarction (TIMI) flow grade <3, which was determined by the TIMI frame count method using angiographic images obtained just after PCI and stenting. RESULTS Compared with patients without ARB treatment, patients with ARB had more frequently hypertension and ST resolution (P < 0.05), but no significant difference was found in the other clinical characteristics (age, sex, Hyperlipidaemia, Diabetes mellitus, etc) between the two groups. A total of 51 patients receiving chronic ARB treatment before admission have lower incidence of the no-reflow phenomenon than those without chronic ARB treatment (8.7% and 26.7%, P= 0.003). However, the incidence of the no-reflow phenomenon between the patients with and without hypertension had no significant difference. Multivariable logistic regression analysis revealed that ARB pretreatment was a significant predictor of the no-reflow phenomenon, whereas blood pressure was found to be insignificant. CONCLUSION Chronic pretreatment of ARB is associated with the reduction of the no-reflow phenomenon in patients with reperfused AMI and could preserve microvascular integrity after AMI independent of blood pressure lowering, which may contribute to better functional recovery.

The key features of percutaneous coronary intervention with chronic total obstruction lesion of right coronary artery

We summarize recent research on percutaneous coronary intervention of chronic total occlusion of the right coronary artery. We then explain the method and technology of forward and backward revascularization in chronic total occlusion of the right coronary artery. Finally, we emphasize the monitoring methods and key treating measures for better prognosis of the patients.

INITIAL AND LONG-TERM CLINICAL OUTCOMES OF UNPROTECTED LEFT MAIN STENTING USING DRUG ELUTING STENTS

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.