Breviscapine inhibits high glucose-induced proliferation and migration of cultured vascular smooth muscle cells of rats via suppressing the ERK1/2 MAPK signaling pathway.

AIM: To investigate the influences of breviscapine, a flavonoid extracted from Erigeron breviscapus, on the proliferation and migration of vascular smooth muscle cells (VSMCs) cultured in a high glucose medium and the underlying mechanisms. METHODS: VSMCs were isolated from thoracic aortas of male Sprague-Dawley rats and cultured in vitro. Cell proliferation was evaluated using Counting Kit-8 cell viability assay. Cell migration was evaluated using transwell migration assay and in vitro scratch assay. The expression and activity of protein kinase C-ß2 (PKC-ß2), extracellular signal-regulated kinase 1/2 (ERK1/2), p38 mitogen-activated protein kinase (p38), and JNK mitogen-activated protein kinase (JNK) were measured with Western blotting. RESULTS: Exposure of VSMCs to a high glucose (25 mmol/L) medium significantly increased the proliferation and migration potential as compared to the control group. Pretreatment with breviscapine (65 µmol/L and 108 µmol/L) attenuated high glucose-enhanced proliferation and migration of VSMCs. Exposure of VSMCs to the high glucose medium activated both the PKC-ß2 and ERK1/2 MAPK, but not the p38 and JNK MAPK. Pretreatment with breviscapine (65 µmol/L and 108 µmol/L) blocked high glucose-induced increase of the ERK1/2 activity, but not that of the PKC-ß2 activity. CONCLUSION: Our study demonstrated that breviscapine ameliorates high glucose-induced proliferation and migration of VSMCs via inhibiting ERK1/2 MAPK signaling.

[Safety and efficacy of transradial percutaneous coronary intervention for unprotected left main coronary artery lesions with 6 French guiding catheter].

OBJECTIVE: To investigate the safety, medium-term and long-term efficacy of transradial percutaneous coronary intervention for unprotected left main coronary artery lesions with 6 French guiding catheter. METHODS: Sixty-one patients with unprotected left main coronary artery lesions were treated by 6 French transradial percutaneous coronary intervention between January 2008 and December 2009. The mean age of patients was (66.03 ±10.02)years (44-87). Among 61 cases, 40 had hypertension and 14 had diabetes mellitus; 22 had a history of smoking. The average left ventricle ejection fraction was (62.96 ±12.15)% (range: 28-86) and the average plasma creatinine level was (82.92 ±18.30)µmol/L (range: 44-130). The major adverse cardiac events (MACE) after the procedure were evaluated. RESULTS: Procedural success was achieved in all cases. A total of 67 stents were implanted. No in-hospital death occurred. Mean clinical follow-up period was (26.25 ±5.92) months (range: 19-44 months). MACE developed in 6 cases (9.8%) during the follow-up period, including 2 death (3.3%) and 4 case of target lesion revascularization (6.6%). Compared with low-risk group (SYNTAX score<33), MACE was increased in the high-risk group (SYNTAX score>32). CONCLUSION: 6 French transradial percutaneous coronary intervention for patients with unprotected left main coronary artery lesions is safe and feasible procedure with desirable medium-and long-term outcomes.

[Effects of proton pump inhibitors on in-stent restenosis in patients receiving clopidogrel: a retrospective analysis].

OBJECTIVE: To determine the effect of proton pump inhibitor (PPI) on in-stent restenosis (ISR) in patients receiving clopidogrel therapy. METHODS: Total 439 patients underwent percutaneous coronary intervention (PCI) were enrolled in the study,including 250 post-PCI patients discharged on clopidogrel alone and 189 patients discharged on clopidogrel with PPI. The in-stent restenosis (ISR) ratio of the patients in these two groups were observed. RESULTS: During a mean follow-up period of (13 ± 5.9) months, the post-PCI patients discharged on concomitant clopidogrel-PPI therapy had higher risk of ISR than those discharged on clopidogrel alone (19.6% Compared with 8%, P<0.001). CONCLUSION: Concomitant use of clopidogrel and PPI after hospital discharge would increase the risk of ISR for post-PCI patients.

Comparison of rotational atherectomy and modified balloons prior to drug-eluting stent implantation for the treatment of heavily calcified coronary lesions.

ABSTRACT: The optimal strategy for lesion preparation in heavily calcified coronary lesions (HCCL) prior to drug-eluting stent (DES) implantation remains debatable. This study sought to compare the performance of rotational atherectomy (RA) and modified balloon (MB)-based strategy in patients with HCCL receiving current-generation DES.This retrospective study comprised 564 consecutive patients who underwent RA (n = 229) or MB (n = 335) for HCCL at our hospital and were treated with DES. Baseline clinical and angiographic data was obtained from our database. Patients were clinically monitored for the occurrence of any adverse events during the hospitalization. One-year follow-up was conducted by either telephone contact or outpatient visits. 1:1 propensity score matching (PSM) was performed to balance the baseline covariates. After PSM, the clinical outcomes between the 2 groups were compared.After PSM, except more target lesion in right coronary artery existing in the RA group (P = .008), no significant statistical differences were shown in regard of the other angiographic and procedural characteristics of the 2 groups. Strategy success rates were all 100% in both groups. In the unadjusted Cox proportional hazard analysis, participants with RA had a significantly lower risk of target lesion revascularization (TLR) (hazard ratio, HR 0.275, 95% confidence intervals, CI 0.119-0.635, P = .003) and major adverse cardiac event (MACE) (HR 0.488, 95% 0.277-0.859, P = .013). After adjusting for potential confounding variables, RA was significantly associated with TLR (HR 0.32, 95% 0.12-0.853, P = .023), but no longer significantly associated with MACE (HR 0.674, 95% 0.329-1.381, P = .282).In patients with HCCL, lesion preparation with RA was safe and could improve strategy success rate. There was lower rate of TLR with RA, however, no significant difference was found in the MACE rate at 1-year follow-up between RA and MB-based strategy.

Breviscapine ameliorates hypertrophy of cardiomyocytes induced by high glucose in diabetic rats via the PKC signaling pathway.

AIM: To investigate the influence of breviscapine on high glucose-induced hypertrophy of cardiomyocytes and the relevant mechanism in vitro and in vivo. METHODS: Cultured neonatal cardiomyocytes were divided into i) control; ii) high glucose concentrations; iii) high glucose+PKC inhibitor Ro-31-8220; iv) high glucose+breviscapine; or v) high glucose+NF-kappaB inhibitor BAY11-7082. Cellular contraction frequency and volumes were measured; the expression of protein kinase C (PKC), NF-kappaB, TNF-alpha, and c-fos were assessed by Western blot or reverse transcription-polymerase chain reaction (RT-PCR). Diabetic rats were induced by a single intraperitoneal injection of streptozotocin, and randomly divided into i) control rats; ii) diabetic rats; or iii) diabetic rats administered with breviscapine (10 or 25 mg x kg(-1) x d(-1)). After treatment with breviscapine for six weeks, the echocardiographic parameters were measured. All rats were then sacrificed and heart tissue was obtained for microscopy. The expression patterns of PKC, NF-kappaB, TNF-alpha, and c-fos were measured by Western blot or RT-PCR. RESULTS: Cardiomyocytes cultured in a high concentration of glucose showed an increased pulsatile frequency and cellular volume, as well as a higher expression of PKC, NF-kappaB, TNF-alpha, and c-fos compared with the control group. Breviscapine could partly prevent these changes. Diabetic rats showed relative cardiac hypertrophy and a higher expression of PKC, NF-kappaB, TNF-alpha, and c-fos; treatment with breviscapine could ameliorate these changes in diabetic cardiomyopathy. CONCLUSION: Breviscapine prevented cardiac hypertrophy in diabetic rats by inhibiting the expression of PKC, which may have a protective effect in the pathogenesis of diabetic cardiomyopathy via the PKC/NF-kappaB/c-fos signal transduction pathway.

[The effect of chelerythrine on the hypertrophy of cardiac myocytes of neonatal rats induced by different glucose levels and its mechanism].

The purpose of this study is to investigate the effect of chelerythrine on the hypertrophy of cardiomyocytes of neonatal rats induced by different glucose levels and its mechanism. Using cultured neonatal ventricular myocytes as a model, groups were divided as: control (5 mmol x L(-1)); high glucose level (10, 15, 20, and 25.5 mmol x L(-1)); high glucose level (25.5 mmol x L(-1)) add different concentrations of chelerythrine (1 and 8 micromol x L(-1)); and control glucose level (5 mmol x L(-1)) add different concentrations of chelerythrine (1 and 8 micromol x L(-1)). Different groups of cardiomyocytes after adding corresponding treat factors were cultured for 48 hours. Cardiomyocytes' diameters and protein level were measured and the expression of PKC-alpha, PKC-beta2, p-PKC-alpha, and p-PKC-beta2 were measured by Western blotting. Compared with control group, neonatal myocytes cultured in high glucose levels showed increased cellular volumes, protein level and expression of PKC-alpha, PKC-beta2, p-PKC-alpha, p-PKC-beta2. When chelerythrine was added, cellular volumes, protein level and expression of PKC-alpha, PKC-beta2, p-PKC-alpha, p-PKC-beta2 were significantly reduced. But in 1 micromol x L(-1) chelerythrine group, the expression of PKC-beta2 was not significantly reduced. The result suggested that chelerythrine can reverse the hypertrophy induced by different glucose levels on the cardiac myocytes, it may have protective effect against diabetic cardiomyopathy via PKC passageway.

[Treatment of coronary bifurcation lesions with 6F-guiding catheter by transradial approach].

OBJECTIVE: To investigate the feasibility and safety in treatment of coronary bifurcation lesions with 6F-guiding catheter by transradial approach. METHODS: Clinical data of 1258 patients who were treated with 6F-guiding catheter by transradial approach from Oct. 2003 to Feb. 2007 were reviewed. The most common approach in the treatment of bifurcations was one-stent technique on the main branch; if the side branch was large enough and the lesion was involved in the ostium and proximal part of side branch, two-stent technique was used. RESULT: Of 295 bifurcation lesions, 204 were originally planed to be treated by one stent; but finally 2 side branches were provisional stented due to dissection in this group. Ninety-one cases were planed to use double-stent technique: 73 with crushing stent (46 step crushing, 24 modified balloon crushing, 3 reverse crushing), 5 with T-stent, 3 with Cullote-stent, 5 with modified V-stent, 5 with step kissing stent. There was no acute myocardial infarction or death occurred but 1 case was complicated with cardiac tamponade secondary from coronary perforation. CONCLUSION: The treatment of coronary bifurcation lesions with 6F-guiding catheter by transradial approach is a feasible and safe procedure.

[Study on the terahertz spectrum of Haojiami].

Haojiami is a very effective drug to treat malaria, and as a result of its unique drug efficacy, it is widely used in the clinical medicine. It was studied experimentally by terahertz (THz) time-domain spectroscopy (THz-TDS), and the characteristic absorption spectra were obtained in the range of 0.2 to 3.0 THz. In parallel with the experimental study, the density functional theory (DFT) and 6-31G basis set were applied to obtain the structure and vibrational frequencies of the haojiami molecule. The observed vibrational spectra were assigned according to the DFT calculations. Theoretical results show that 1.26 and 2.73 THz in significant agreement with experimental results at 1.24 and 2.73 THz. At the same time, haojiami's far infrared vibration pattern was recognized. The vibration mode takes the molecular groups skeleton vibration and the reverse as the chief feature. The results suggest that the use of the THz-TDS technique can be an effective way to inspect for Chinese medicine, and provide the theory basis for further study of the haojiami drug efficacy.

Magainin-modified polydopamine nanoparticles for photothermal killing of bacteria at low temperature.

Photothermal therapy (PTT) is a promising method to kill bacteria because of the broad-spectrum of antibacterial activity and the ability of spatiotemporal regulation. In the previously reported systems, light induced high temperature (˜70 °C) was essential for effectively killing of bacteria, which, however, would also damage nearby nontarget cells or tissues. Here we report photothermal nanoparticles (NPs) for more targeting and killing bacteria at a relative low temperature. Polydopamine (PDA) was chosen to prepare NPs because of its excellent capability of photothermal conversion. Magainin I (MagI) which is an antimicrobial peptide was used to modify NPs' surface because it can specifically interact with bacteria. We demonstrate that MagI-PEG@PDA NPs effectively killed E. coli at a low temperature of ˜45 °C upon near-infrared (NIR) light irradiation. In contrast, the native PDA NPs under light irradiation or the MagI-PEG@PDA NPs themselves showed no bacteria killing ability. This work highlights the importance of close interaction between the target bacteria and the photothermal materials and may promote the practical clinical applications of the PTT.

[Influence of various glucose levels on the structure and function of cultured neonatal rats cardiomyocytes].

OBJECTIVE: To study the influence of various glucose levels on the structure and function of cultured neonatal rats cardiomyocytes. METHOD: Cultured neonatal ventricular cardiomyocytes were treated with various glucose levels for 5 days: control (5.5 mmol/L); high (25.5 mmol/L); intermittent high (5.5 mmol/L or 25.5 mmol/L in every 12 hours interval); high (25.5 mmol/L) + PKC inhibitor Ro-31-8220 (50 nmol/L). Then, the cell beating frequency was counted, the cardiomyocytes diameters were measured and the expressions of PKC-alpha, PKC-beta(2), p-PKC-alpha, p-PKC-beta(2), NF-kappaB and c-fos were determined by Western blot. RESULTS: Compared with control group, cardiomyocytes beating frequency, diameters as well as the expressions of PKC-alpha, PKC-beta(2), p-PKC-alpha, p-PKC-beta(2), NF-kappaB and c-fos were significantly increased in high glucose concentration (all P < 0.05) and intermittent high glucose treatment further amplified these changes (all P < 0.05 vs. high glucose and control groups). High glucose induced changes could be significantly attenuated with PKC inhibitor Ro-31-8220. CONCLUSION: High, especially intermittent high glucose could lead to diabetic cardiomyopathy by promoting cardiac hypertrophy, increasing beating frequency via activating PKC/NF-kappaB/c-fos pathways.

[Mechanism and re-ablation strategy for postablation atrial tachyarrhythmia in atrial fibrillation patients].

OBJECTIVE: To investigate the mechanism and re-ablation strategy of recurrent atrial tachyarrhythmia (ATA) following circumferential ablation of pulmonary veins (PV) in patients with atrial fibrillation (AF). METHODS: Fifteen patients with recurrent ATA following first AF ablation procedure were included in this study. Under CARTO guidance, PVs were remapped and ablated subsequently for relapse of left atrium to PV conduction. The whole atrium was then remapped and individualized ablation was made to eliminate inducible ATA. RESULTS: Left atrium to PV conduction relapses were evidenced in 14 patients. After re-ablation, there were no inducible ATA in 9 patients, inducible left atrial macro-reentry tachycardia in 3 patients and all were terminated by further linear ablation on the roof and left atrial isthmus, inducible atrial focal tachycardia from left atrial isthmus in 1 patient and was eliminated after additional focal ablation, inducible right atrial macro-reentry tachycardia in 2 patients and were eliminated by right isthmus linear ablation. During 1 - 16 (5.5 +/- 4.4) months follow-up, ATA was disappeared in 13 patients and reduced in another 2 patients. CONCLUSIONS: Relapse of left atrium to PV conduction is one of the main mechanisms for postablation ATA in patients with AF. Atrial macro-reentry tachycardia and focal atrial tachycardia were less common mechanisms for postablation ATA. Re-ablation focused on closing the PV gaps and additional individualized focal and lineal ablation strategies were helpful for treating postablation ATA in AF patients.

Effect of a distal protection device on epicardial blood flow and myocardial perfusion in primary percutaneous coronary intervention.

OBJECTIVE: The beneficial effect of percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI) has been well established, but there is the problem of no-reflow phenomenon which is an adverse prognostic factor in primary PCI. In the present study the effect of a distal protection device (PercuSurge GuardWire; GW) on epicardial blood flow and myocardial perfusion was evaluated. METHODS AND RESULTS: Patients with AMI were randomly divided into 2 groups, the GW and the control groups. The GW group included 52 patients with AMI who underwent primary PCI with GW protection and the control group included 60 patients who underwent primary PCI without GW protection. Epicardial blood flow in the infarct-related artery (IRA) and myocardial perfusion were evaluated according to the thrombolysis in myocardial infarction (TIMI) flow grade and the myocardial blush grade (MBG). We found TIMI score of 3 was obtained significantly more frequently in the GW group (96%) than in the control group (80%). The MBG score of 3 was obtained also significantly greater in the GW group (65%) than in the control group (33%). CONCLUSION: Primary PCI with GW protection can significantly improve epicardial blood flow and myocardial perfusion.

The analysis of ultrastructure and gene expression of sarco/endoplasmic reticulum calcium handling proteins in alloxan-induced diabetic rat myocardium.

OBJECTIVE: The change of mechanical properties of isolated diabetic rat papillary muscle, myocardial ultrastructure and gene expression of sarco/endoplasic reticulum calcium handling proteins in alloxan-induced diabetic rat heart was investigated. METHODS: Diabetes was induced in male Sprague-Dawley rats (180-220 g) by administering a single tail-vein injection (40 mg/kg) of alloxan. The control group was injected with normal saline. At the end of 2, 4 and 6 weeks after the induction of diabetes, the right ventricular papillary muscles were isolated and perfused with oxygen saturated Tyrode solution for assessment of the contractile function. Light and electron microscopic analysis was used to analyse the myocardial ultrastructure in rats six weeks after induction. Gene expression of calcium handling proteins was measured by reverse transcription-polymerase chain reaction and Western blot. RESULTS: In the diabetic rats, +dT/dtmax and -dT/dtmax were decreased (P < 0.01), while 1/2 diastolic intervals were longer than control at the end of 4 and 6 weeks (P < 0.01). Electron microscopic analysis of the myocardium revealed a spectrum of subcellular remodelling which was characterized by damaged myofibrils and mitochondria and dilated swollen sarcoplasmic reticulum. The levels of both mRNA and protein of phospholamban were significantly increased, whereas 1, 4, 5-trisphophate inositol receptor type 2, ryanodine receptor type 2 mRNAs were significantly decreased compared with that in the age-matched 6 weeks control rats. In contrast, levels of both mRNA and protein of sarco/endoplasic reticulum Ca2+ -ATPase were not affected. CONCLUSIONS: Contractile dysfunction of papillary muscles and subcellular remodelling exist in alloxan-induced diabetic rat myocardium. Up-regulation of phospholamban and down-regulation of sarco/endoplasic reticulum calcium release channel may be the molecular mechanism.

Segmental radiofrequency ablation of pulmonary vein ostia for patients with refractory paroxysmal atrial fibrillation using multi-slice spiral computed tomography guidance.

OBJECTIVE: To evaluate the safety and clinical efficacy of segmental radiofrequency ablation of pulmonary vein (PV) ostia for patients with refractory paroxysmal atrial fibrillation (AF) under multi-slice spiral computed tomography (MSCT) guidance before the procedure. METHODS: A series of 58 consecutive patients with refractory paroxysmal AF were enrolled to undergo segmental radiofrequency ablation of PV ostia. The 36 male and 22 female patients with mean age of (57.4+/-9.5) (32-79) years and no obvious organic heart disease. Before ablation, patients received MSCT to generate 3-dimensional image of the left atrium (LA) and proximal PVs. Patients then underwent segmental radiofrequency ablation of PV ostia using PV circular mapping catheter manipulated several times to ensure complete isolation between PVs and LA. RESULTS: No complications occurred during the procedure. One patient developed delayed cardiac tamponade, which was drained percutaneously. The mean follow-up time was (17.1+/-9.3) months. Forty-one patients (95%) experienced improved quality of life one month after the procedure. Thirty-six patients (83%) showed stable sinus rhythm, while 10 patients (23%) required additional anti-arrhythmic drugs. AF returned> or =1 time in 6 (14%) patients who underwent anti-arrhythmic drug therapy, but the number of episodes was less than that before the procedure. However, one patient experienced recurrent episodes of atrial flutter. CONCLUSION: It is safe and effective to perform segmental radiofrequency ablation of PV ostia for patients with refractory paroxysmal AF using MSCT guidance mappening.

[Alterations of myocardial ultrastructure and gene expression of calcium handling proteins in diabetic rat heart].

OBJECTIVE: To investigate the ultrastructure of myocardium and gene expression of calcium handling proteins in diabetic rat heart. METHODS: Diabetes was induced in male Sprague-Dawley rats by a single injection of alloxanm (40 mg/kg ) and the rats in control group were injected with normal saline. At the end of 2, 4, 6 weeks after the induction of diabetes, the animals were sacrificed. The expression of calcium handling proteins was detected by reverse transcription-polymerase chain reaction (RT-PCR) and actin mRNA was used as internal standard. Heart tissue at the apex was obtained for light and electron microscope study. RESULTS: At the end of 4 and 6 weeks, cardiosomatic ratio of diabetic rats was higher than that of control. Electron microscopy revealed a spectrum of subcellular remodeling in myocardium which was characterized by damaged myofibrils and mitochondria, dilated and swollen sarcoplasmic reticulum. Expression of phospholamban mRNAs was significantly increased, but 1,4,5-trisphosphate inositol receptor type 2, ryanodine receptor type 2 mRNAs were significantly decreased compared with those in the age-matched control rats. In contrast, the expression of sarco/endoplasmic reticulum Ca(2+)-ATPase mRNAs was not affected. CONCLUSION: In diabetic rat heart, gene expression of calcium handling proteins was characterized by up-regulation of phospholamban and down-regulation of sarcoplasmic reticulum calcium release channel while electron microscopic analysis of myocardium revealed a spectrum of subcellular remodeling.

[Tissue Doppler imaging evaluate the effect of optimal biventricular resynchronization for congestive heart disease in left ventricular synchrony and function].

OBJECTIVE: To evaluate the immediate change of left ventricular systolic performance and asynchronization between simultaneous biventricular pacing and sequential biventricular pacing by tissue synchronization imaging (TSI) and tissue velocity imaging (TVI) in patients with congestive heart failure. The effect of sequential biventricular resynchronization therapy was also observed. METHODS: Ten patients with dilated cardiomyopathy who received sequential biventricular resynchronization were enrolled. The TVI and TSI imagings were performed by GE vivid7 with M3S probe. The left ventricular ejection fraction (LVEF), stroke volume (SV), aortic velocity time integral (VTI), left ventricular end diastolic diameter (LVEDd), the standard deviation of the electro-mechanical delay (EMD-SD) of 6 segments and TSI index were measured before implanting of InSync 8042 and 1 month, 3 months, 6 months after implanting respectively. RESULTS: After 6 months of implanting, the LVEF, SV and VTI were obviously increased from (22.0 +/- 8.8)% to (38.0 +/- 9.9)%; (36.0 +/- 14.9) ml to (57.0 +/- 15.7) ml; (20.22 +/- 5.72) cm to (26.20 +/- 5.98) cm, P < 0.05, respectively, compared with the before of implanting. The LVEDd was decreased from (6.6 +/- 0.6) cm, to (6.0 +/- 0.9) cm, P < 0.05. The EMD-SD and TSI-index were declined gradually after implanting, which was more evident in the 6 months after implanting, from (83.07 +/- 46.99) ms to (22.37 +/- 16.38) ms; (2.20 +/- 0.36) to (1.50 +/- 0.43), P < 0.05, respectively, but the immediate EMD-SD did not change obviously between simultaneous biventricular pacing and sequential biventricular pacing, whereas, the TSI index and VTI were significantly improved from (1.87 +/- 0.31) to (1.71 +/- 0.29); (22.44 +/- 5.43) cm to (25.44 +/- 5.36) cm, P < 0.05, respectively, in the sequential biventricular pacing. CONCLUSION: Sequential biventricular resynchronization could improve the left ventricular systolic function and synchronism of wall motion in the patients with congestive heart failure, which is more effective than simultaneous biventricular pacing after implanting immediately.

Paracrine effects of bone marrow-derived endothelial progenitor cells: cyclooxygenase-2/prostacyclin pathway in pulmonary arterial hypertension.

BACKGROUND: Endothelial dysfunction is the pathophysiological characteristic of pulmonary arterial hypertension (PAH). Some paracrine factors secreted by bone marrow-derived endothelial progenitor cells (BMEPCs) have the potential to strengthen endothelial integrity and function. This study investigated whether BMEPCs have the therapeutic potential to improve monocrotaline (MCT)-induced PAH via producing vasoprotective substances in a paracrine fashion. METHODS AND RESULTS: Bone marrow-derived mononuclear cells were cultured for 7 days to yield BMEPCs. 24 hours or 3 weeks after exposure to BMEPCs in vitro or in vivo, the vascular reactivity, cyclooxygenase-2 (COX-2) expression, prostacyclin (PGI2) and cAMP release in isolated pulmonary arteries were examined respectively. Treatment with BMEPCs could improve the relaxation of pulmonary arteries in MCT-induced PAH and BMEPCs were grafted into the pulmonary bed. The COX-2/prostacyclin synthase (PGIS) and its progenies PGI2/cAMP were found to be significantly increased in BMEPCs treated pulmonary arteries, and this action was reversed by a selective COX-2 inhibitor, NS398. Moreover, the same effect was also observed in conditioned medium obtained from BMEPCs culture. CONCLUSIONS: Implantation of BMEPCs effectively ameliorates MCT-induced PAH. Factors secreted in a paracrine fashion from BMEPCs promote vasoprotection by increasing the release of PGI2 and level of cAMP.

Breviscapine ameliorates cardiac dysfunction and regulates the myocardial Ca(2+)-cycling proteins in streptozotocin-induced diabetic rats.

To investigate the influence of breviscapine on the cardiac structure and function in diabetic cardiomyopathy rats as well as the expression of protein kinase C (PKC) and Ca(2+)-cycling proteins expression. Diabetes was induced in male Sprague-Dawley rats by a single intraperitoneal injection of streptozotocin and the control rats were injected with saline. After the induction of diabetes for 4 weeks, the animals were divided into different groups: (1) normal rats as control; (2) diabetic rats; (3) diabetic rats with administration of breviscapine (10 or 25 mg kg(-1) day(-2)). After treatment with breviscapine for 6 weeks, the invasive cardiac function and echocardiographic parameters were measured, and heart tissue was obtained for electron microscope study. The expression of protein kinase C (PKC) and calcium handling regulators, such as protein phosphatase inhibitor-1 (PPI-1), phospholamban (PLB) and Ca(2+)-ATPase (SERCA-2), ryanodine receptor (RyR) were detected by western blot or RT-PCR. The activity of SERCA-2 was measured using Ca(2+)-ATPase kit. Diabetic rats showed impaired cardiac structure and function compared with control rats. The expression of PKC, PLB increased significantly, while the PPI-1, SERCA-2 and RyR expression decreased. Treatment with breviscapine could reverse the cardiac dysfunction and structure changes in diabetic cardiomyopathy rats, and decrease the expression of PKC and PLB, as well as increase the expression of PPI-1, SERCA-2 and RyR. The protective effect of breviscapine was dose related. This study showed that breviscapine could regulate the expression of PKC, PPI-1, PLB and SERCA-2 and have protective effect on diabetic cardiomyopathy.