Combining CHA2DS2-VASc score into RCRI for prediction perioperative cardiovascular outcomes in patients undergoing non-cardiac surgery: a retrospective pilot study.

BACKGROUND: Treatment decisions in patients undergoing non-cardiac surgery are based on clinical assessment. The Revised Cardiac Risk Index (RCRI) is pragmatic and widely used but has only moderate discrimination. We aimed to test the efficacy of the CHA2DS2-VASc score and the combination of CHA2DS2-VASc and RCRI to predict perioperative risks for non-cardiac surgery. METHODS: This pre-specified analysis was performed in a retrospective cohort undergoing intra-abdominal surgery in our center from July 1st, 2007 to June 30th, 2008. The possible association between the baseline characteristics (as defined by CHA2DS2-VASc and RCRI) and the primary outcome of composite perioperative cardiac complications (myocardial infarction, cardiac ischemia, heart failure, arrhythmia, stroke, and/or death) and secondary outcomes of individual endpoints were explored using multivariate Logistic regression. The area under the receiver operating characteristic curve (C-statistic) was used for RCRI, CHA2DS2-VASc, and the combined models, and the net reclassification improvement (NRI) was calculated to assess the additional discriminative ability. RESULTS: Of the 1079 patients (age 57.5 ± 17.0 years), 460 (42.6%) were women. A total of 83 patients (7.7%) reached the primary endpoint. Secondary outcomes included 52 cardiac ischemic events, 40 myocardial infarction, 20 atrial fibrillation, 18 heart failure, four strokes, and 30 deaths. The endpoint events increased with the RCRI and CHA2DS2-VASc grade elevated (P < 0.05 for trend). The RCRI showed a moderate predictive ability with a C-statistics of 0.668 (95%CI 0.610-0.725) for the composite cardiac outcome. The C-statistics for the CHA2DS2-VASc was 0.765 (95% CI 0.709-0.820), indicating better performance than the RCRI (p = 0.011). Adding the CHA2DS2-VASc to the RCRI further increased the C-statistic to 0.774(95%CI 0.719-0.829), improved sensitivity, negative predictive value, and enhanced reclassification in reference to RCRI. Similar performance of the combined scores was demonstrated in the analysis of individual secondary endpoints. The best cut-off of a total of 4 scores was suggested for the combined CHA2DS2-VASc and RCRI in the prediction of the perioperative cardiac outcomes. CONCLUSIONS: The CHA2DS2-VASc score significantly enhanced risk assessment for the composite perioperative cardiovascular outcome in comparison to traditional RCRI risk stratification. Incorporation of CHA2DS2-VASc scores into clinical-decision making to improve perioperative management in patients undergoing non-cardiac surgery warrants consideration.

Genetic polymorphisms of UTS2 rs2890565 Ser89Asn in cardiac hypertrophy in Chinese Han population.

OBJECTIVE: Cardiac hypertrophy is the heart's response to a variety of extrinsic and intrinsic stimuli, some of which might finally lead up to a maladaptive state. Clinical evidence, in vitro and in vivo studies have implicated urotensin II (U-II/UTS2) in the development of cardiac hypertrophy, contributing to the (patho)-physiological regulation of cardiovascular homeostasis in humans. Several genes are associated with left ventricular hypertrophy; considering these, our objective was to evaluate the possible role of UTS2 gene polymorphisms (Thr21Met and Ser89Asn) in the genetic susceptibility to cardiac hypertrophy in a Chinese population. METHODS: A case-control study was designed to compare the distribution of alleles and genotypes between three groups: case group 1 (subjects with hypertension and cardiac hypertrophy, n=265), case group 2 (subjects with hypertension, without cardiac hypertrophy, n=768), and the control group (subjects neither with hypertension nor with cardiac hypertrophy, n=416). The detection of UTS2 gene polymorphisms was achieved with the PCR restriction fragment length polymorphism technique. RESULTS: We did not identify statistically significant differences between the three groups, neither with regard to the frequency of genotype/variant at the Ser89Asn locus nor at the Thr21Met locus. When stratified by sex, differences in genotype distribution of polymorphism Ser89Asn were only seen in female subjects in both the additive tested inheritance model (OR=0.507, 95% CI 0.249 to 1.032, p=0.032) and the recessive tested inheritance model (OR=0.475, 95% CI 0.239 to 0.945, p=0.034) between case group 2 (subjects with hypertension, without cardiac hypertrophy) and the control group (subjects neither with hypertension nor with cardiac hypertrophy). When stratified by sex, for female subjects with cardiac hypertrophy, we identified statistically significant differences in left ventricular posterior wall thickness for variant genotypes at the Ser89Asn locus (AA vs GG: 1.2500 (1.2000, 1.3750) vs 1.2500 (1.2000, 1.3750), p=0.03) and (AG+AA vs GG: 1.2000 (1.2000, 1.3000) vs 1.2000 (1.1000, 1.2000), p=0.01). CONCLUSIONS: Ser89Asn (S89N) polymorphisms of the UTS2 gene were associated with hypertension in a Chinese female population. Additionally, we demonstrated that genotype Asn89Asn was associated with left ventricular posterior wall thickness for subjects with hypertension and cardiac hypertrophy in a Chinese female population.

Role of UTS2 gene in the genetic susceptibility to atrial fibrillation in the Chinese population.

OBJECTIVE: Atrial fibrosis plays a key role in the inducibility and persistence of atrial fibrillation. Urotensin II (U-II/UTS2) induces cardiac fibrosis by increasing fibroblast collagen synthesis and increased U-II plasma levels have been reported in patients with atrial fibrosis. Our objective was therefore to evaluate the possible role of the UTS2 gene polymorphisms Thr21Met and Ser89Asn in the genetic susceptibility to atrial fibrillation in a Chinese population. METHODS: A case-control study was designed to compare the distribution of alleles and genotypes between controls (n=197) and patients with AF (n=197). The detection of UTS2 gene polymorphisms was undertaken using the PCR-restriction fragment length polymorphism technique. RESULTS: We identified statistically significant differences between the atrial fibrillation and control groups with regard to the frequency of genotype variant GA at the Ser89Asn locus (OR 1.955, 95% CI 1.071 to 3.566, p=0.029). When stratified by sex, differences in genotype distribution of polymorphism Ser89Asn was only seen in men in the additive tested inheritance model (OR 2.843, 95% CI 1.273 to 6.348, p=0.011). There was a statistical difference in Met21Met, implying a potential beneficial role for atrial fibrillation in the recessive tested inheritance model among men (OR 0.260, 95% CI 0.075 to 0.89, p=0.033; AA vs GA-GG). For subjects with atrial fibrillation, the Met21Met genotype was associated with a larger anteroposterior left atrial diameter (AA vs GG, 4.12±0.62 vs 3.86±0.51, p=0.028) and a smaller left ventricular end-diastolic diameter (AA vs GG, 4.50±0.48 vs 4.78±0.49, p=0.039). CONCLUSIONS: Ser89Asn polymorphisms of the UTS2 gene are significantly associated with atrial fibrillation in the Chinese population. Additionally, we demonstrated that genotype Met21Met may have a potential beneficial role in atrial fibrillation.

Synthesis of stable isotopically labelled 3-methylfuran-2(5H)-one and the corresponding strigolactones.

Conventional synthetic procedures of strigolactones (SLs) involve the independent synthesis of ring ABC and ring D, followed by a coupling of the two fragments. Here we prepared three kinds of stable, isotopically labelled D-ring analogues productively using a facile protocol. Then, a coupling of the D-rings to ring ABC produced three isotope-labelled SL derivatives. Moreover, (+)-D3-2'-epi-1A and (-)-ent-D3-2'-epi-1A with high enantiomeric purity were obtained via chiral resolution.

[Left atrial size predicts adverse cardiac events in patients with non-obstruction hypertrophic cardiomyopathy].

OBJECTIVE: To evaluate the relationship between left atrial size and the risk of cardiac events in patients with non-obstruction hypertrophic cardiomyopathy. METHODS: In the study, 39 patients who met inclusion criteria were followed up for (28.0±7.7) months. The patients were divided into two groups with or without major adverse cardiac events (a composite of arrhythmia, angina, syncope and congestive heart failure). Clinical and echocardiographic data of the two groups were compared. The predictive value of left atrial diameter (LAD) and left atrial volume index (LAVI) were reviewed by using receive operating characteristic curve (ROC). The events analysis was performed by using the Kaplan-Meier analysis. RESULTS: Cardiac events occurred in 11 patients (28.2%). LAD, LAD index (LADI), LAV and LAVI were significantly greater in the patients with cardiac events than those without cardiac events [LAD: (4.28±0.63) cm vs. (3.85±0.48) cm, P=0.025; LADI: (0.048 9±0.011 1) cm/m(2) vs. (0.040 8±0.005 8) cm/m(2), P=0.005; LAV: (60.8±16.2) mL vs. (46.2±14.0) mL, P=0.008; LAVI: (66.5±23.8) mL/m(2) vs. (49.6±15.9) mL/m(2), P=0.014]. An LAD of >4.29 cm identified patients with cardiac events with a sensitivity of 63.6% and a specificity of 89.3%. An LAVI of >53.1 mL/m(2) identified patients with cardiac events with a sensitivity of 72.7% and a specificity of 71.4%. The Kaplan-Meier analysis indicated that the patients with LAD>4.29 cm or LAVI>53.1 mL/m(2) had higher incidence of cardiac events. CONCLUSION: LAD and LAVI may be effective markers for predicting adverse cardiac events in patients with non-obstruction hypertrophic cardiomyopathy.

Catestatin as a predictor for cardiac death in heart failure with mildly reduced and preserved ejection fraction.

AIMS: Endogenous catecholamine release-inhibitory peptide catestatin has been associated with heart failure (HF). This subgroup analysis of our cohort of HF compared the different effects of catestatin as a predictor for cardiac outcomes in patients with HF with reduced (HFrEF), mildly reduced (HFmrEF) or preserved (HFpEF) ejection fraction. METHODS: Plasma catestatin was measured in the HF patient cohort of 228 cases with a whole spectrum of ejection fraction. The cardiac deaths were analysed according to prespecified subgroups. RESULTS: Over a median follow-up of 52.5 months, the association between plasma catestatin and cardiac death was different in patients with HFrEF, HFmrEF or HFpEF [hazard ratio (HR) 1.53, 95% confidence interval (CI) 0.99-2.37 and HR 2.73, 95% CI 1.56-4.75, respectively; interaction P = 0.022]. Patients with HFmrEF/HFpEF were older and more likely to be female, with non-ischaemic cardiomyopathy and atrial fibrillation but lower levels of plasma B-type natriuretic peptide (BNP). Similar adverse cardiac events occurred in patients with HFmrEF/HFpEF as in HFrEF. Plasma catestatin was a better predictor for cardiovascular death in the HFmrEF/HFpEF patients [area under the receiver operating characteristic curve (AUC) = 0.72, 95% CI 0.45-0.74] than in the HFrEF patients (AUC = 0.59, 95% CI 0.587-0.849). The optimal cut point of plasma catestatin level of 0.86 ng/mL predicted a 2.80-fold elevated risk for cardiac death in HFmrEF/HFpEF. CONCLUSIONS: Elevated plasma catestatin might be a more sensitive predictor for cardiac outcome in patients with HFmrEF/HFpEF than in HFrEF.

Plasma catestatin level in patients with acute myocardial infarction and its correlation with ventricular remodelling.

BACKGROUND: The evaluation of ventricular remodelling and functional recovery is essential in predicting the prognosis of patients with acute myocardial infarction (AMI). OBJECTIVE: To determine the plasma catestatin level in patients with AMI, and investigate the association between plasma catestatin and heart function, and with left ventricular remodelling (LVR). METHODS: Fifty-eight consecutive patients who were admitted within 12 h of the onset of their ST-segment elevation myocardial infarction symptoms between 1 October 2009 and 30 June 2011 were prospectively recruited. Circulating catestatin was measured by ELISA. All patients underwent an echocardiography examination during the first week; 31 patients had a second echocardiography examination 3 months after the myocardial infarction. RESULTS: Plasma catestatin at the time of admission was significantly higher in patients than in normal controls. The level increased further in the first week after AMI. Three months after AMI, the plasma catestatin level of patients was comparable to that of normal controls. The plasma level of catestatin correlated with anterior AMI and left ventricular ejection fraction (LVEF) in the acute stage. Compared with patients without LVR, those with LVR had significantly higher level of plasma brain natriuretic peptide on day 7 and a significantly higher level of plasma catestatin on admission and on days 3 and 7 (p=0.033, p=0.001, p=0.006, p=0.021, respectively). CONCLUSIONS: Plasma catestatin levels were raised after AMI. An early increase of catestatin correlated with anterior AMI and LVEF. Plasma catestatin after the onset of AMI might be associated with the magnitude of progressive ventricular remodelling 3 months after AMI.

[Plasma osteopontin level and left ventricular remodeling in patients with acute myocardial infarction].

OBJECTIVE: To investigate the change of plasma osteopontin level during the progress of acute ST-segment elevation myocardial infarction, as well as its association with the left ventricular remodeling and prognosis. METHODS: In the study, 61 patients with acute ST-segment elevation myocardial infarction were recruited. Blood samples were taken at admission, on the 3rd day and 7th day of admission, while 63 healthy blood donors were employed as normal controls. There plasma osteopontin levels were measured by ELSIA. RESULTS: Compared with the normal controls, the plasma osteopontin levels of the patients with acute ST-segment elevation myocardial infarction were significantly higher at admission [(96.51±37.22) µg/L vs. (54.50±28.17) µ g/L, P<0.001], reached the peak value on the 3rd day, and dropped down on the 7th day. The correlation analysis showed that the plasma osteopontin level positively correlated with age and left ventricular end-systolic volume index 3 months after acute myocardial infarction, and negatively correlated with left ventricular ejection fraction 3 months after acute myocardial infarction. The follow-up study found that the plasma osteopontin level did not predict mortality, re-infarction, stroke, revascularization or hospitalization due to heart failure. CONCLUSION: In patients with acute ST-segment elevation myocardial infarction, the elevated plasma level of osteopontin might be associated with the left ventricular remodeling.

[Analysis of perioperative cardiovascular events and related risk factors in patients undergoing intraperitoneal surgery].

OBJECTIVES: To investigate incidence of perioperative cardiovascular events, to analyze related risk factors for the patients undergoing intraperitoneal surgery. METHODS: The data of 1079 patients who underwent intraperitoneal surgery (exclude laparoscope surgery) from July 2007 to June 2008 was reviewed and analyzed. RESULTS: For the patients undergoing intraperitoneal surgery, the incidence of major cardiovascular events was 3.99% (43/1079), all-cause mortality was 1.58% (17/1079). The independent risk factors of major cardiovascular events were age ≥ 60 years, history of coronary heart disease, cardiac insufficiency, arrhythmia, chronic obstructive pulmonary disease, estimated glomerular filtration rate (eGFR) < 60 ml/(min·1.73 m(2)), emergency surgery and duration of surgery > 2.82 h (OR = 2.68 to 5.19, P = 0.001 to 0.031). CONCLUSIONS: The cardiac risk of intraperitoneal surgery is 3.99%. The risk of cardiac complications should be evaluated in elderly patients and those with ischaemic heart disease, chronic obstructive pulmonary disease, and renal disease, more specifically, when emergent or long duration major surgeries are needed.

All-solid photonic band gap fiber based distributed fiber optic pressure sensor.

A novel distributed fiber optic pressure sensor based on an all-solid photonic band gap fiber is proposed and experimentally demonstrated. The sensor is fabricated by splicing a piece of the photonic crystal fiber (PCF) with a single-mode fiber (SMF), and the free end face of the PCF is filmed with a reflectivity of 99%. The cladding mode is excited at the fiber splice, resulting in the interference between the cladding mode and the core mode. The pressure position can be located by measuring the phase difference of the interferometer, and the pressure can be interrogated by measuring the height of the valley in the white-light optical spectrum. The experimental results show that the pressure and its position along the PCF can be simultaneously interrogated.

Differences in perioperative cardiovascular outcomes in elderly male and female patients undergoing intra-abdominal surgery: a retrospective cohort study.

OBJECTIVE: Perioperative cardiovascular events constitute the majority of complications in noncardiac surgery. Older and female patients have been less investigated. We aimed to evaluate differences in perioperative cardiovascular outcomes by age and sex. METHODS: We enrolled 1079 patients (57.5 ± 17.0 years, 42.6% women) undergoing intra-abdominal surgery from July 2007 to June 2008 and compared occurrence of perioperative cardiac events by age (≥65 vs. <65 years) and sex. Multivariable logistic regression was used to investigate associations between age, sex, and outcomes. RESULTS: Age ≥65 years was associated with perioperative myocardial infarction (MI) (odds ratio [OR] 2.9, 95% confidence interval [CI]: 1.3-6.6) and total cardiovascular events (OR 2.4, 95% CI: 1.3-4.2). Age ≥65 years was associated with higher perioperative MI risks in men (OR 4.7, 95% CI: 1.3-17.6) than in women (OR 3.1, 95% CI: 1.2-8.3). Advanced age was associated with heart failure in women (OR 13.9, 95% CI: 1.7-110.5). Female sex was a risk factor for heart failure in elderly patients (OR 4.2, 95% CI: 1.1-15.7). CONCLUSIONS: Advanced age appeared to be associated with increased perioperative cardiac risk but differed by sex. Tailored strategies should be considered with respect to the patient's sex.

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.

Catestatin in defense of oxidative-stress-induced apoptosis: A novel mechanism by activating the beta2 adrenergic receptor and PKB/Akt pathway in ischemic-reperfused myocardium.

Apoptosis induced by oxidative stress is one of the most important cardiomyocytes losses during ischemia-reperfusion (I/R). Catestatin (CST) has been demonstrated to have the anti-oxidative capacity in vitro. We hypothesized that CST intervention could reduce apoptosis of cardiomyocytes induced by oxidative stress in I/R. In Langendorff-perfused rat heart global I/R model, CST was introduced at the reperfusion stage. In comparison to the control group, CST led to preservation on activities of superoxide dismutase and glutathione peroxidase, improvement of hemodynamics, and reduced infarction area in reperfused myocardium. The protection of CST was also shown by less apoptotic cardiomyocytes in TUNEL staining, less caspase-3 activation, and increased phosphorylation of protein kinase B (PKB/Akt) in Western blot. To further demonstrate the benefits of CST and explore the possible underlying mechanism, H2O2-challenged primary-cultured neonatal rat cardiomyocytes were used to simulate the oxidative-stressed scenario. CST incubation with the H2O2-challenged cardiomyocytes led to reduction of apoptosis, which was demonstrated by less Hoechst 33342 positive staining of nuclei, less caspase-3 activation, and DNA fragmentation. The effect of CST was abrogated by pretreatment of the cardiomyocytes with the PI3K inhibitor LY294002. Furthermore, Akt activation and the anti-apoptosis effect of CST were abolished by pretreatment of the cardiomyocytes with ß2 receptor inhibitor ICI118551. Thus, the salvage of oxidative-stress-induced apoptotic cardiomyocytes in I/R by CST might involve activation ß2 receptor and regulation of PI3K/Akt signaling in reperfusion injury salvage kinase (RISK) pathway.

[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.

Influence of OATP1B1 and OATP1B3 mutations and glomerular filtration rate on trough serum digoxin concentration in the Chinese population: A prospective cohort study.

Polymorphisms of organic anion transporting polypeptides (OATPs) have been reported to affect trough serum digoxin concentration (SDC). However, the association of these polymorphisms with trough SDC in Chinese heart failure patients has not been studied. We aim to explore whether OATP1B1 388A>G, OATP1B1 521T>C, and OATP1B3 699G>A influence trough SDC in Chinese heart failure patients and to make clinical recommendations.Chinese patients (n = 104) diagnosed with heart failure under long-term digoxin therapy (0.125 mg daily) were enrolled in this study. Blood samples were collected for the analysis of trough SDC (immunofluorescence) and the polymorphisms of OATP1B1 388A>G, OATP1B1 521T>C, and OATP1B3 699G>A (PCR-RFLP and Sanger sequencing).Patients with glomerular filtration rate (GFR) under 30 mL/min had significantly higher trough SDC (1.20 ±â€Š0.50 ng/mL) than recommended trough SDC for heart failure patients. Trough SDC was not significantly influenced by mutations of OATP1B1 388A>G (P = .890), 521T>C (P = .054), and OATP1B3 699G>A (P = .854). Patients with OATP1B1 521T>C mutant-type carrier had slightly higher trough SDC (0.98 ±â€Š0.53 ng/mL) than those with wild-type carrier (0.74 ±â€Š0.40 ng/mL) when they have repaired renal function.Heart failure patients with severe renal dysfunction (GFR<60 mL/min) and/or OATP1B1 521T>C mutant-type carriers are recommended a smaller dosage of digoxin and strict therapeutic drug monitoring.

[In vivo interleukin-10 gene transfer down-regulates myocardial matrix metalloproteinase and myocardial collagen expressions in rats with acute myocardial infarction].

OBJECTIVE: We investigated the in vivo effects of recombinant adenovirus-associated virus type-2 (AAV-2) mediated interleukin-10 (IL-10) gene transfer on the expression of matrix metalloproteinase (MMP)-2, 9, tissue inhibitor of metalloproteinase (TIMP)-1, collagen type I and type III in a rat acute myocardial infarction model. METHOD: Male Sprague-Dawley (SD) rats were randomly divided into three groups (each n = 6): sham operation group, MI/AAV2 group, and MI/AAV2-IL-10 group (10(10) vg/ml x 0.1 ml injection at peri-infarct regions immediately post MI). Five days later, the expressions of MMP-2 and MMP-9 were measured by RT-PCR, Western blot and zymography. The expression of TIMP-1 was measured by RT-PCR and Western blot. Collagen type I and type III were assessed by RT-PCR and immunohistochemical stain. RESULTS: The myocardial expressions of MMP-2, MMP-9 and collagen contents in MI/AAV2 group were significantly increased than those in sham operation group. Myocardial expressions of MMP-2, MMP-9 were significantly decreased and the expression of TIMP-1 significantly increased in the MI/AAV2-IL-10 group than those in MI/AAV2 group. Moreover, the expressions of collagen type I, collagen type III and the ratio of I/III collagen in border zones of infarcted myocardium were decreased by 47.6% (P < 0.01), 23.6% (P < 0.05), and 17.9% (P < 0.05) respectively, while the expression of TIMP-1 increased by 73.1%(P < 0.05) in MI/AAV2-IL-10 group compared to MI/AAV2 group. CONCLUSION: In vivo myocardial IL-10 transfer reduced myocardial MMP and collagen expression and increasing the TIMP expression.

Genetic polymorphisms of UTS2 rs2890565 Ser89Asn in coronary heart disease and myocardial infarction in Chinese population.

OBJECTIVE: Atherosclerosis plays a key role in the inducibility and persistence of coronary heart disease. Clinical evidence, in vitro and in vivo studies have implicated Urotensin II (U-II/UTS2) in the development of atherosclerosis and coronary artery disease, contributing to the (patho) physiological regulation of cardiovascular homeostasis in humans. Increased U-II plasma levels have been reported in patients with atherosclerosis and coronary heart disease. Considering these, our objective was to evaluate possible role of the UTS2 gene polymorphisms (Thr21Met and Ser89Asn) in the genetic susceptibility to coronary heart disease and myocardial infarction in a Chinese population. METHODS: A case-control study was designed to compare the distribution of alleles and genotypes between case group (subjects with myocardial infarction, n=409) and control group (subjects with coronary heart disease, n=830). The detection of UTS2 gene polymorphisms was achieved with PCR-RFLP technique. RESULTS: We did not identify statistically significant differences between the myocardial infarction and coronary heart disease groups, neither with regard to the frequency of genotype/variant at the Ser89Asn locus nor at the Thr21Met locus. When stratified by sex, differences in genotype distribution of polymorphism Ser89Asn were only seen in female subjects in both additive tested inheritance model (OR=0.257, 95% CI: 0.074-0.896, P=0.033) and recessive tested inheritance model (OR=0.280, 95% CI: 0.082-0.955, P=0.042). For subjects with myocardial infarction, we identified statistically significant differences between the ST-segment elevation myocardial infarction and non ST-segment elevation myocardial infarction groups. Differences in genotype distribution of polymorphism Ser89Asn not Thr21Met were seen in both additive tested inheritance model (OR=0.202, 95% CI: 0.049-0.833, P=0.027) and recessive tested inheritance model (OR=0.208, 95% CI: 0.052-0.835, P=0.027). When stratified by sex, differences in genotype distribution of polymorphism Ser89Asn were only seen in male subjects in both additive tested inheritance model (OR=0.208, 95% CI: 0.049-0.890, P=0.034) and recessive tested inheritance model (OR=0.197, 95% CI: 0.047-0.824, P=0.026). CONCLUSIONS: Ser89Asn (S89N) polymorphisms of the UTS2 gene were significantly associated with coronary heart disease and myocardial infarction in Chinese population. Additionally, we demonstrated that Genotype Asn89Asn may imply a potential benefit role for myocardial infarction.

Urotensin II promotes aldosterone expression in rat aortic adventitial fibroblasts.

Urotensin II (UII) contributes to cardiovascular diseases by activating vasoactive peptides. The present study aimed to determine the effect of UII on aldosterone (ALD) and its receptor in cultured adventitial fibroblasts (AFs) and the tunica adventitia of rat vessels to explore the possible mechanisms underlying vascular remodeling. Expression levels of aldosterone and its receptor on tunica adventitia were determined using immunohistochemistry. Growth­arrested AFs and tunica adventitia from rat vessels were incubated with UII and inhibitors of various signal transduction pathways. ALD receptor (ALD­R) mRNA expression levels and ALD protein exoression levels were determined by reverse transcription­quantitative polymerase chain reaction and ELISA, respectively. Aldosterone and its receptors were expressed on tunica adventitia. UII promoted ALD protein secretion from cells in a dose­ and time­dependent manner. ALD­R mRNA expression in cells was also dysregulated. Furthermore, the effects of UII were substantially inhibited by treatment with the inhibitors PD98059, Y­27632, H­7, CSA and nicardipine. These results were further verified in the tunica adventitia of rat vessels. The present findings indicated that UII stimulated ALD protein secretion and ALD­R mRNA expression in AFs and in the tunica adventitia of rat vessels; moreover, this effect may be mediated by signal transduction pathways involving MAPK, Rho, PKC, calcineurin and Ca2+. UII may also contribute to vascular remodeling by stimulating the production of ALD and its receptor.