Thawing plateau time indicating the duration of phase transition from ice to water is the strongest predictor for long-term durable pulmonary vein isolation after cryoballoon ablation for atrial fibrillation-Data from the index and repeat procedures.

Introduction: This study aimed to clarify the relationship between the durability of pulmonary vein (PV) isolation and the time of phase transition from ice to water indicated by thawing plateau time in a cryoballoon ablation for atrial fibrillation (AF). Methods and results: In this retrospective study, 241 PVs from 71 patients who underwent a repeat AF ablation 526 (IQR: 412, 675) days after a cryoballoon ablation were analyzed. Reconnection was observed in 101 (41.9%) PVs of 53 patients (74.6%). Thawing plateau time (TimeTP) was defined as the time from 0°C to 10°C inside the balloon in the thawing period. Durable PV isolation was associated with significantly longer TimeTP compared with PV reconnection (26.0 vs. 11.0 s, P < 0.001). The proportion of durable PV isolations increased with TimeTP in a dose-proportional manner. The cut point for PV reconnection was TimeTP <15 s with a positive predictive value of 82.1% (sensitivity = 63.4%, specificity = 90.0%) while for durable PV isolation the cut point was TimeTP >25 s with a positive predictive value of 84.6% (sensitivity = 55.0%, specificity = 86.1%). In the analysis of multivariable logistic regression, location of PV reconnection (P < 0.01), TimeTP (P < 0.05) and thawing plateau integral (P < 0.01) were shown as independent predictors for durable PV isolation. Conclusion: TimeTP is an independent predictor for the durability of PV isolation, and it presents in a dose-proportional manner. TimeTP <15 s predicts long-term reconnection while TimeTP >25 s predicts durable PV isolation.

Biaxial strain improving carrier mobility for inorganic perovskite:ab initioBoltzmann transport equation.

Inorganic halide perovskites have attracted interest due to their high efficiency and low cost. Considering the uncertainty of experimental measurements, it was important to predict the upper limit of carrier mobility. In this study, theab initioBoltzmann transport equation, including all electron-phonon interactions, was used to accurately predict the mobilities of CsPbI3, CsSnI3, CsPbBr3, and CsSnBr3. Using the iterative Boltzmann transport equation (IBTE), the calculated mobility for CsPbI3isµe= 512/µh= 379 cm2 V-1 s-1, and Sn-based perovskite exhibited high hole mobility. The longitudinal optical phonons associated with the stretching between halogen anions and divalent metal cations were revealed to be the dominant scattering source for the carriers. Furthermore, the effect of biaxial strain on mobility was investigated. We observed that biaxial compressive strain could improve the mobility of CsPbI3and CsPbBr3. Surprisingly, under a compressive strain of-2%, the mobilities of CsPbI3using IBTE approach were improved toµe= 1176/µh= 936 cm2 V-1 s-1. It was revealed that the compressive strain could decrease the effective mass of CsPbI3and CsPbBr3.

Cryoballoon vs. radiofrequency catheter ablation: insights from NOrwegian randomized study of PERSistent Atrial Fibrillation (NO-PERSAF study).

AIMS: Pulmonary vein isolation (PVI) is still regarded as a cornerstone for treatment of persistent atrial fibrillation (AF). This study evaluated the effectiveness of PVI performed with cryoballoon ablation (CBA) in comparison with radiofrequency ablation (RFA) in patients with persistent AF. METHODS AND RESULTS: A total of 101 patients with symptomatic persistent AF were enrolled and randomized (1:1) to CBA or RFA groups and followed up for 12 months. The primary endpoint was any documented recurrent atrial tachyarrhythmia (ATA) lasting longer than 30 s following a 3-month blanking period. Secondary endpoints were procedure-related complications, procedure and ablation duration, and fluoroscopy time. The ATA-free survival curves were estimated by Kaplan-Meier method and analysed by the log-rank test. According to intention-to-treat analysis, freedom from ATA was achieved in 36 out of 52 patients in the CBA group and 30 out of 49 patients in the RFA group (69.2% vs. 61.2%, P = 0.393). No difference in AF recurrence was found between the two groups (27.5% in CBA vs. 38.0% in RFA, P = 0.258), and less atrial flutter recurrence was documented in the CBA group compared with the RFA group (3.9% vs. 18.0%, P = 0.020). The procedure and ablation duration were significantly shorter in the CBA group (160 ± 31 vs. 197 ± 38 min, P < 0.0001; 36.7 ± 9.5 vs. 55.3 ± 16.7 min, P < 0.0001). There was no difference regarding fluoroscopy time (21.5 ± 7.8 vs. 23.4 ± 11.2 min, P > 0.05). CONCLUSION: Compared with RFA, PVI performed by CBA led to shorter procedure and ablation duration, with less atrial flutter recurrence and similar freedom from ATA at 12-month follow-up.

The impacts of contact force, power and application time on ablation effect indicated by serial measurements of impedance drop in both conventional and high-power short-duration ablation settings of atrial fibrillation.

BACKGROUND: This study aimed to clarify the interrelationship and additive effects of contact force (CF), power and application time in both conventional and high-power short-duration (HPSD) settings. METHODS: Among 38 patients with paroxysmal atrial fibrillation who underwent first-time pulmonary vein isolation, 787 ablation points were collected at the beginning of the procedure at separate sites. Energy was applied for 60 s under power outputs of 25, 30 or 35 W (conventional group), or 10 s when using 50 W (HPSD group). An impedance drop (ID) of 10 Ω was regarded as a marker of adequate lesion formation. RESULTS: ID ≥ 10 Ω could not be achieved with CF < 5 g under any power setting. With CF ≥ 5 g, ID could be enhanced by increasing power output or prolonging ablation time. ID for 30 and 35 W was greater than for 25 W (p < 0.05). Ablation with 35 W resulted in greater ID than with 30 W only when CF of 10-20 g was applied for 20-40 s (p < 0.05). Under the same power output, ID increased with CF level at different time points. The higher the CF, the shorter the time needed to reach ID of 10 Ω and maximal ID. ID correlated well with ablation index under each power, except for lower ID values at 25 W. ID with 50 W for 10 s was equivalent to that with 25 W for 40 s, but lower than that with 30 W for 40 s or 35 W for 30 s. CONCLUSIONS: CF of at least 5 g is required for adequate ablation effect. With CF ≥ 5g, CF, power output, and ablation time can compensate for each other. Time to reach maximal ablation effect can be shortened by increasing CF or power. The effect of HPSD ablation with 50 W for 10 s is equivalent to conventional ablation with 25 W for 40 s and 30-35 W for 20-30 s in terms of ID.

Origin of phonon-limited mobility in two-dimensional metal dichalcogenides.

Metal dichalcogenides are novel two-dimensional (2D) semiconductors after the discovery of graphene. In this article, phonon-limited mobility for six kinds of 2D semiconductors with the composition of MX2is reviewed, in which M (Cr, Mo and W) is the transition metal, and X (S and Se) is the chalcogen element. The review is divided into three parts. In the first part, we briefly introduce the calculation method of mobility, including the empirical model and Boltzmann transport theory (BTE). The application scope, merits and limitations of these methods are summarized. In the second part, we explore empirical models to calculate the mobility of MX2, including longitudinal acoustic phonon, optical phonon (OP) and polar optical phonon (POP) models. The contribution of multi-valley to mobility is reviewed in the calculation. The differences between static and high-frequency dielectric constants (Δϵ) are only 0.13 and 0.03 for MoS2and WS2. Such a low value indicates that the polarization hardly changes in the external field. So, their mobility is not determined by POP, but by deformation potential models. Different from GaAs, POP scattering plays a decisive role in its mobility. Our investigations also reveal that the scattering from POP cannot be ignored in CrSe2, MoSe2and WSe2. In the third parts, we investigate the mobility of MX2using electron-phonon coupling matrix element, which is based on BTE from the framework of a many-body quantum-field theory. Valence band splitting of MoS2and WS2is induced by spin-orbit coupling effect, which leads to the increase of hole mobility. In particular, we review in detail the theoretical and experimental results of MoS2mobility in recent ten years, and its mobility is also compared with other materials to deepen the understanding.

The Roles of Fractionated Potentials in Non-Macroreentrant Atrial Tachycardias Following Atrial Fibrillation Ablation: Recognition Beyond Three-Dimensional Mapping.

Introduction: Non-macroreentrant atrial tachycardia (nAT) following atrial fibrillation (AF) ablation is being increasingly reported. Many issues remain to be elucidated. We aimed to characterize the fractionated potentials (FPs) in nAT and introduce a new method of cross-mapping for clarifying their roles. Methods and Results: Forty-four nATs in 37 patients were enrolled and classified into focal AT (FAT, 12), microreentrant AT (MAT, 14), and small-loop-reentrant AT (SAT, 18) groups, according to activation pattern. FP was found on all targets except in nine FATs. The ratio of FP duration to AT cycle length (TCL) was different among groups (28 ± 7% in FAT, 53 ± 11% in MAT, and 42 ± 14% in SAT, p < 0.05), and ablation duration were longer in SATs (313 ± 298 vs. 111 ± 125 s, p < 0.05). The ratio of mappable cycle length to TCL was lower in the FAT group (63 ± 22% vs. 90 ± 9% and 89 ± 8%, p < 0.05). When cross-mapping was employed, trans-potential time differences in both longitudinal and transverse direction were longer around the culprit FP for MAT (p < 0.01). After Receiver Operating Characteristic curve analysis, it is best to adopt the sum of time difference ratios in both directions ≥60% as a cut-off value for discrimination of the FPs responsible for MAT with a sensitivity of 92% and specificity of 87%. Conclusions: FP could be found on target in most nATs following a previous AF ablation. The ratio of FP duration to TCL may help for differentiation. A simple method of cross-mapping could be employed to clarify the roles of FPs.

Investigation of strain behavior and carrier mobility of organic-inorganic hybrid perovskites: (C4H9NH3)2GeI4 and (C4H9NH3)2SnI4.

Two dimensional (2D) organic-inorganic hybrid perovskites have attracted great interest due to their tunable band gap and structural stability. In this study, biaxial strain behavior and carrier mobility of monolayers (C4H9NH3)2GeI4 and (C4H9NH3)2SnI4 are investigated by first principles calculations. (C4H9NH3)2GeI4 and (C4H9NH3)2SnI4 still retain their structural stability at ε = 13% and ε = 15%, respectively. Ab initio molecular dynamics (AIMD) simulation has confirmed that the system at 300 K is still thermodynamically stable at a biaxial strain of ε = 8%. The band gaps of (C4H9NH3)2GeI4 and (C4H9NH3)2SnI4 calculated from the HSE06 functional are increased from 2.427 and 1.953 eV at zero strain to 3.002 and 2.626 eV at ε = 8%. Deformation potential (DP) models based on longitudinal acoustic phonon (LAP) and optical phonon (OP) scattering are used to investigate mobility. The mobility of (C4H9NH3)2GeI4 is lower than that of (C4H9NH3)2SnI4. It is mainly determined by the scattering from OP with lower energy and decreases sharply with an increase in biaxial strain. Compared with Pb based perovskites, (C4H9NH3)2SnI4 exhibits high carrier mobility and thermodynamic stability.

Theoretical prediction of intrinsic electron mobility of monolayer InSe: first-principles calculation.

Recently, a novel two-dimensional (2D) semiconductor, InSe, has attracted great attention due to its potential applications in optoelectronic devices and field effect transistors. In this study, phonon-limited mobility is investigated by the first-principles calculation. At 300 K, the intrinsic electron mobilities calculated from the electron-phonon coupling (EPC) matrix element are as high as [Formula: see text] (zigzag direction) and [Formula: see text] [Formula: see text] (Armchair direction), respectively. The deformation potential theory (DPT) based on longitudinal acoustic and optical phonon scattering is also employed to investigate electron mobility. The mobility from optical phonon scattering is much higher than that from longitudinal acoustic phonon scattering. If the polarization characteristics of InSe are not considered, the electron mobility calculated from EPC matrix element is closed to that from the longitudinal acoustic phonon DPT. In this study, we have also investigated the effect of polarization properties in 2D InSe on electron mobility. At 300 K, the electron mobility for including Fröhlich interaction is reduced to [Formula: see text] and [Formula: see text] [Formula: see text]. Therefore, the electron mobility for InSe is controlled by the scattering from polar phonons. The mobility can be increased to [Formula: see text] and [Formula: see text] [Formula: see text] under 4% biaxial strain. This result is compared with the experiment, and some disagreements are explained.

Giant magnetic anisotropy of rare-earth adatoms and dimers adsorbed by graphene oxide.

Nowadays, transition-metal adatoms and dimers with giant magnetic anisotropy have attracted much attention due to their potential applications in data storage, spintronics and quantum computations. Using density-functional calculations, we investigated the magnetic anisotropy of the rare-earth adatoms and dimers adsorbed by graphene oxide. Our calculations reveal that the adatoms of Tm, Er and Sm possess giant magnetic anisotropy, typically larger than 40 meV. When the dimers of (Tm,Er,Sm)-Ir are adsorbed onto graphene oxide, the magnetic anisotropy even exceeds 200 meV. The magnetic anisotropy can be tuned by the external electric field as well as the environment.

Incidence and clinical predictors of subsequent atrial fibrillation requiring additional ablation after cavotricuspid isthmus ablation for typical atrial flutter.

OBJECTIVES: We sought to investigate the incidence of atrial fibrillation after catheter ablation for typical atrial flutter and to determine the predictors for symptomatic atrial fibrillation that required a further additional dedicated ablation procedure. DESIGN: 127 patients underwent elective cavotricuspid isthmus ablation with the indication of symptomatic, typical atrial flutter. The occurrence of atrial flutter, atrial fibrillation, cerebrovascular events and the need for additional ablation procedures for symptomatic atrial fibrillation was assessed during long-term follow-up. RESULTS: The majority of patients (70%) manifested atrial fibrillation during a follow-up period of 68 ± 24 months, and a significant proportion (42%) underwent one or multiple atrial fibrillation ablation procedures after an average of 26 months from the index procedure. Recurrence of typical atrial flutter was rare. Ten patients (8%) suffered cerebrovascular events. Earlier documentation of atrial fibrillation (OR 3.53), previous use of flecainide (OR 3.33) and left atrial diameter (OR 2.96) independently predicted occurrence of atrial fibrillation during the follow-up. A combination of pre- and intra-procedural documentation of atrial fibrillation (OR 3.81) and previous use of flecainide (OR 2.43) independently predicted additional atrial fibrillation ablation. DISCUSSION: Atrial fibrillation occurred in the majority of patients after ablation for typical atrial flutter and 42% of them required an additional dedicated ablation procedure. Pre- and intraprocedural documentation of atrial fibrillation together with previous use of flecainide independently predicted atrial fibrillation occurrence and a need for additional ablation. Anticoagulation treatment should be continued in high-risk patients in spite of clinical disappearance of atrial flutter.

Abnormal glucose regulation in Chinese patients with coronary artery disease: A cross-sectional study.

The purpose of this study was to investigate the prevalence of abnormal glucose regulation (AGR) in patients with established coronary artery disease (CAD), and the association of AGR and acute coronary events in Chinese patients.A total of 3441 hospitalized patients with established diagnosis of CAD were recruited from 41 centers in 25 cities of China. Oral glucose tolerance test (OGTT) was performed in 2112 patients without known diabetes. Acute coronary events were recorded for the patients.AGR was detected in 1880 (89%) patients in the OGTT cohort, with 1265 (59.9%) diagnosed with impaired glucose tolerance, 363 (17.2%) diagnosed with diabetes, and 30 (1.4%) diagnosed with isolated impaired fasting glucose. The overall proportion of patients diagnosed with diabetes increased from 30.7% (n = 930) at baseline to 42.6% (n = 1298) following the OGTT analysis. In total 85% (n = 3047) patients in the study was diagnosed with AGR. Multivariate analysis showed that AGR was independently associated with acute coronary events, after adjusting for the traditional risk factors including age, smoking, hypertension, and hyperlipidemia.The prevalence of AGR is increasing in Chinese patients with CAD, as compared with previous report. AGR was independently associated with acute coronary events. Prospective studies are warranted to evaluate the benefit of intervening prediabetes in adult patients with CAD.

Effect of flecainide on the extension and localization of complex fractionated electrogram during atrial fibrillation.

AIMS: Complex fractionated electrogram (CFE) ablation in addition to pulmonary vein isolation is an accepted strategy for the treatment of non-paroxysmal atrial fibrillation (AF). We sought to determine the effect of flecainide on the distribution and extension of CFE areas. METHODS: Twenty-three non-paroxysmal AF patients were enrolled in this prospective study. A first CFE map was obtained under baseline conditions by sampling 5 s of continuous recording from the distal electrodes of the ablation catheter. Intravenous flecainide (1 mg/kg) was administered over 10 min and followed by 30-min observation time. A second CFE map was obtained with the same modalities. CFE-mean values, CFE areas, and atrial electrogram amplitude were retrieved from the electro-anatomical mapping system (Ensite NavX). RESULTS: After flecainide administration, CFE-mean values increased (111.5 ± 55.3 vs. 132.3 ± 65.0 ms, p < 0.001) with a decrease of CFE area (32.9%) in all patients. Atrial electrogram amplitude decreased significantly (0.30 ± 0.31 vs. 0.25 ± 0.20 mV, p < 0.001). We observed 80.9% preservation of CFE areas. A CFE mean of 78 ms was the best cutoff for predicting stable CFE areas. CONCLUSIONS: Flecainide reduces the extension of CFE areas while preserving their spatial localization. A CFE-mean value <80 ms may be crucial to define and locate stable CFE areas.

Effects of exogenous urotensin II on vascular remodelling after balloon injury.

1. Urotensin II (U-II) is a powerful vasoconstrictor peptide that stimulates cell proliferation. However, the systemic effects of U-II on cellular and extracellular matrix responses of vessel walls have not been investigated. The aim of the present study was to determine the effect of exogenous U-II on arterial neointimal hyperplasia after balloon injury. 2. A stenosis model of the thoracic aorta after balloon injury was established in male Wistar rats. Rats were divided into three groups (n = 5 in each): (i) uninjured; (ii) injured for 21 days; and (iii) injured and then treated with U-II (1 nmol/kg per h) via an osmotic minipump for 21 days. Another group of rats were killed on Days 7 and 14 after balloon injury for the analysis of in vitro collagen synthesis and secretion with U-II treated by [(3)H]-proline incorporation and determination of [(3)H]-hydroxyproline radioactivity, respectively. 3. Urotensin II immunoreactivity was 1.74-fold higher in vessels injured for 21 days than in uninjured vessels and mRNA levels of the urotensin UT receptor were upregulated by 55% following injury. After U-II treatment, the mRNA levels of the UT receptor were further upregulated (by 40%). In addition, U-II treatment increased the intimal area of injured aortas (13 +/- 5 vs 7 +/- 2% in group iii and ii, respectively), as well as increasing collagen content and cell proliferation. Protein levels of matrix metalloproteinase 1 were decreased in U-II-treated rats. In vitro, U-II treatment increased collagen synthesis and secretion in uninjured vessels in a concentration-dependent manner (10(-10), 10(-9) and 10(-8) mol/L U-II), especially in injured aortas on Day 7 after injury. 4. In conclusion, exogenous U-II may upregulate mRNA levels of the UT receptor, as well as increase collagen and cell proliferation, all of which would contribute to intimal hyperplasia after angioplasty.

[Cardiovascular events in patients with chronic kidney disease].

OBJECTIVE: Cardiovascular event is common and is an important cause of death for patients with chronic kidney disease (CKD). The purpose of current study is to analyze the related risk factors of cardiovascular event in patients with CKD. METHODS: Clinical data from 557 patients with CKD (stage III-V) who hospitalized in our hospital from Jan 2006 to Dec 2006 were retrospectively analyzed focusing on the risk factors of cardiovascular event and their impacts on death. RESULTS: Among the 557 patients with CKD, 332 were male and 225 were female. There were totally 163 patients (163/557, 29.3%) suffered from cardiovascular events during hospitalization. The independent risk factors for cardiovascular event were age, history of coronary heart disease, anemia and fasting blood glucose level. The mortality was significantly higher in patients suffered from cardiovascular events than that in patients without cardiovascular events (9.82% vs. 2.28%, P<0.001). CONCLUSIONS: For patients with CKD, anemia is another independent risk factor for cardiovascular events besides traditional risk factors and the mortality was significantly higher in CKD patients with cardiovascular events compared to CKD patients without cardiovascular events.

[The clinical features and outcomes of immunoglobulin light-chain amyloidosis with heart involvement].

OBJECTIVE: To analyze the clinical features and outcomes of patients with immunoglobulin light-chain amyloidosis (AL) who had heart involvement. METHODS: Clinical features and outcomes of AL amyloidosis patients with heart involvement in the past 7 years in our hospital were retrospectively analyzed. RESULTS: Cardiac involvement was seen in 36 out of the 60 AL patients (60%). The clinical manifestations of cardiac amyloidosis included heart failure (50%), low QRS voltage (47.2%) and pseudomyocardial infarction (33.3%) in electrocardiography, as well as thickening of ventricular wall (63.9%), echo of granular sparkling texture (11.1%), atria dilation (33.3%) and diastolic dysfunction (30.6%) in echocardiography. The prognosis was poor, with a median survival time of 13.9 months. CONCLUSION: Patients of AL amyloidosis with cardiac involvement are not rare. Thickening of ventricular wall and diastolic dysfunction are the most common characteristics. Special attention should be paid to this disease.

[The effect of different loading doses of clopidogrel on platelet aggregation].

OBJECTIVE: To compare the short-term efficacy and safety of high loading dose (600 mg) clopidogrel treatment with those of routine loading dose (300 mg) in patients with acute coronary syndrome and provide evidence for planning clopidogrel treatment. METHODS: 60 patients were randomized into two groups, One group received 300 mg loading dose clopidogrel, while the other received 600 mg and both were followed by 75 mg daily thereafter. Adenosine diphosphate (ADP) (5 micromol/L and 20 micromol/L) induced platelet aggregation was examined at baseline (before administration), 2 hours and 6 hours after administration and the count of white blood cell and platelet 3 days after loading dose. The primary end points were hemorrhagic events, granulocytopenia and thrombocytopenia within 3 days after administration. RESULTS: With a high-dose agonist (20 micromol/L ADP), loading doses of clopidogrel at 300 mg and 600 mg both produced greater inhibition of baseline ADP (20 micromol/L) induced aggregation 6 hours after administration than 2 hours [group of 300 mg: (29.75+/-12.11)% vs (43.63+/-14.31)%, P<0.05. Group of 600 mg: (28.86+/-10.24)% vs (34.86+/-10.84)%, P<0.05]. Treatment with clopidogrel at 600 mg loading dose had a marked earlier effect on platelet aggregation 2 hours after administration than that of 300 mg [(34.86+/-10.84)% vs (43.63+/-14.31)%, P<0.05]. The platelet aggregation of the two groups tended towards similar at 6 hours after the procedure [(28.86+/-10.24)% vs (29.75+/-12.11)%, P>0.05]. There were no episodes of hemorrhagic events, granulocytopenia and thrombocytopenia within 3 days after the procedure. CONCLUSIONS: In Chinese patients with acute coronary syndrome platelet aggregation can be inhibited more rapidly and more effectively with clopidogrel at 600 mg loading dose when compared with that at 300 mg loading dose and the safety aspect between the two different loading doses is equivalent.

[Effects of oxidized-low density lipoprotein on expression of urotensin II receptor GPR14 in rat aortic smooth muscle cells].

OBJECTIVE: To investigate the effects of oxidized-low density lipoprotein (ox-LDL) and urotensin II (U II) on the proliferation of rat aortic smooth muscle cells (VSMCs) and the effect of ox-LDL on the mRNA expression of U II receptor GPR14 in. METHODS: Rat VSMCs were incubated with UII and ox-LDL at different concentrations. The viability of rat VSMCs was detected by MTT assay. Rat VSMCs were incubated with ox-LDL at the concentrations of 0, 0.1, 1, 10, and 50 microg/ml. Twelve hours later competitive RT-PCR was used to detect the effects of concentration of ox-LDP on the mRNA expression of GPR14 in the VSMCs. Another VSMCs were incubated with ox-LDL at the final concentration of 50 microg/ml, and 0, 2, 6, 12, and 24 hours later competitive RT-PCR was used to detect the mRNA expression of GPR14 in the VSMCs. (125)I-labelled U II was added into the culture fluid of VSMCs, and radioligand binding assay was used to calculate the maximum binding (B(max)). RESULTS: UII of the concentration of 50 nmol/L significantly increased the proliferation of VSMCs. When the concentration of ox-LDL was 10 microg/ml the proliferation of VSMCs (P < 0.01) was 0.678 +/- 0.061, increased by 121% compared with the control group (0.325 +/- 0.052, P < 0.01). 0.01 microg/ml of ox-LDL and 10 nmol/L of UII showed a synergistic effect on the proliferation of VSMCs with the MTT value increased to 162% +/- 29% that of the control group (P < 0.01). When the concentration of ox-LDL increase to 0.1 microg/ml the synergistic effect was attenuated with the MTT value of 153% +/- 22% that of the control group (P < 0.05) and when the concentration of ox-LDL increased to 1 microg/ml the synergistic effect diminished, with a MTT value of 123% +/- 13% that of the control group (P > 0.05). When the concentration of ox-LDL was 50 microg/ml the proliferation of VSMCs the MTT value decreased to 59% that of the of control group, however, ox-LDL of the concentration of 50 microg/ml combined with UII of the concentration of 10 nmol/L the MTT value increased to 68% that of the control group, showing that UII of that concentration significantly inhibited the cytotoxic effect of ox-LDL. Incubation of VSMCs with the ox-LDL at the concentration of 0.1 microg/ml the GPR14 mRNA expression of the VSMCs was 125.1% that of the control group (P < 0.01) as assessed by competitive RT-PCR, however, when the concentration of ox-LDL increased over 1 microg/ml the GPR14 mRNA expression does-dependently decreased as much as 72.6% that of the control group (all P < 0.01), with the maximal effect when the concentration of ox-LDL reached 50 microg/ml. ox-LDL at the concentration of 50 microg/ml time-dependently down-regulated the GPR14 mRNA expression with the maximal effect 12 hours after addition of ox-LDL and this effect was sustained for up to 24 hours. After incubation for 12 hours the binding of (125)I-UII to VSMCs was 117.5% that of the control group (P < 0.01) with the ox-LDL at the concentration of 0.1 microg/ml, and was 68.8% that of the control group (P < 0.01) with the ox-LDL at the concentration of 50 microg/ml. CONCLUSION: ox-LDL and with U-II. GPR14 at certain concentrations show synergetic effects on the proliferation of VSMCs. The GPR14 mRNA expression in VSMCs can be upregulated by low concentration of ox-LDL, while downregulated by high concentration of ox-LDL.

Alteration of vascular urotensin II receptor in mice with apolipoprotein E gene knockout.

Urotensin II (U-II), originally identified as a fish neuropeptide, exerts a broad spectrum of biological functions and is considered to be the most potent vasoconstrictor in mammals. Recently the intense staining of U-II-like immunoreactivity within coronary atheroma and the effect of mitogenic in vascular smooth muscle cells (VSMCs) suggest that U-II is possibly a proatherogenic factor in the pathogenesis of cardiovascular diseases (CVD). In the present study, we analyzed the gene expression of U-II and GPR14, a high-affinity receptor for U-II, in aorta of apolipoprotein E (apoE) -/- mutant mice by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). Compared with wild-type mice at the same age group, GPR14 mRNA level is significant increase in aorta of apoE -/- mice at age of 18, 28 and 38 weeks, respectively. The increased GPR14 mRNA level was 54.2, 50.0 and 97.0% in the three age groups, respectively. We did not detect U-II mRNA expression in aorta either in apoE -/- mice or in wild-type mice. In 28-week mice, ligand-binding assay showed that maximum binding capacity (Bmax) of 125I-U-II aorta from apoE -/- mice was increased by 64%, while the affinity of the binding did not change compared with that of wild-type mice. These results indicate that the up-regulation of vascular U-II receptor (UT), GPR14 might be involved in the pathogenesis of atherosclerosis.