LXRß is involved in the control of platelet production from megakaryocytes.

Liver X receptor ß (LXRß), a nuclear receptor involved in important cellular processes such as cholesterol, glucose and fatty acid metabolism, was suggested to be involved in platelet aggregation but its detailed roles are not clear. In the present study, we evaluated the contribution of LXRß to platelet functions and production. In the systemic collagen-epinephrine thrombosis mouse model, LXRß-deficient mice showed increased area of blood clots compared with control wide-type littermates. The aggregation of LXRß-deficient platelets in response to ADP was stronger than that of control mice platelets. More importantly, the number of platelets in blood of LXRß-deficient mice was significantly higher than that of wild-type mice, especially for female mice. Knockdown of LXRß expression in human megakaryoblastic Dami cells also enhanced cell polyploidization, formation of proplatelets and production of platelet-like particles. Increase in expression levels of proteins related to oxidative phosphorylation such as NADH:ubiquinone oxidoreductase core subunit V1 (Ndufv1) was observed in LXRß-knockdown Dami cells. The levels of Ndufv1 in LXRß-deficient mice platelets were also higher than that of wild-type mice. Taken together, our findings suggested LXRß might participate in control of platelet production from megakaryocytes by regulating mitochondrial metabolism.

Effect of 1,5-anhydroglucitol levels on culprit plaque rupture in diabetic patients with acute coronary syndrome.

BACKGROUND: Postprandial hyperglycemia was reported to play a key role in established risk factors of coronary artery diseases (CAD) and cardiovascular events. Serum 1,5-anhydroglucitol (1,5-AG) levels are known to be a clinical marker of short-term postprandial glucose (PPG) excursions. Low serum 1,5-AG levels have been associated with occurrence of CAD. However, the relationship between 1,5-AG levels and coronary plaque rupture has not been fully elucidated. The aim of this study was to evaluate 1,5-AG as a predictor of coronary plaque rupture in diabetic patients with acute coronary syndrome (ACS). METHODS: A total of 144 diabetic patients with ACS were included in this study. All patients underwent intravascular ultrasound examination, which revealed 49 patients with plaque rupture and 95 patients without plaque rupture in the culprit lesion. Fasting blood glucose (FBG), hemoglobin A1c (HbA1c) and 1,5-AG levels were measured before coronary angiography. Fasting urinary 8-iso-prostaglandin F2α (8-iso-PGF2α) level was measured and corrected by creatinine clearance. RESULTS: Patients with ruptured plaque had significantly lower serum 1,5-AG levels, longer duration of diabetes, higher HbA1c and FBG levels than patients without ruptured plaque in our study population. In multivariate analysis, low 1,5-AG levels were an independent predictor of plaque rupture (odds ratio 3.421; P = 0.005) in diabetic patients with ACS. The area under the receiver-operating characteristic curve for 1,5-AG (0.658, P = 0.002) to predict plaque rupture was superior to that for HbA1c (0.587, P = 0.087). Levels of 1,5-AG were significantly correlated with urinary 8-iso-prostaglandin F2α levels (r = - 0.234, P = 0.005). CONCLUSIONS: Serum 1,5-AG may identify high risk for coronary plaque rupture in diabetic patients with ACS, which suggests PPG excursions are related to the pathogenesis of plaque rupture in diabetes.

Short-term effects of air pollution on acute myocardial infarctions in Shanghai, China, 2013-2014.

BACKGROUND: Although particulate matter, with diameters < 2.5 µm (PM2.5) and < 10 µm (PM10), and other pollutants have been associated with cardiovascular morbidity and mortality, the effect of pollutants on acute myocardial infarctions (AMIs) has rarely been investigated in Asia, especially in Shanghai, China. METHODS: Between 1 November 2013 and 27 April 2014, 972 patients from the Pudong District, Shanghai City, were assessed by the Emergency Medical Service. A case-crossover design was used to analyze exposure to air pollution and the AMI risk. Exposures to PM2.5, PM10, nitrogen dioxide (NO2), sulphurdioxide (SO2), and carbon monoxide (CO) were based on the mean urban background levels. The associations among AMI admissions, the included pollutants, temperature, and relative humidity were analyzed using correlation and logistic regression. RESULTS: The urban background levels of PM2.5, PM10 and CO were associated with an increased risk of AMI, unlike NO2 and SO2 levels. The OR (95% CI) for AMI were 1.16 (1.03-1.29), 1.05 (1.01-1.16), 0.82 (0.75-1.02), 0.87 (0.63-1.95), and 1.08 (1.02-1.21) for PM2.5, PM10, NO2, SO2, and CO, respectively. Increases in the air quality index (AQI) were associated with more AMI occurrences. There was no correlation between fluctuations in temperature and relative humidity with AMI hospital admissions. CONCLUSIONS: Short-term exposure to moderate-serious pollution levels is associated with increased risk of AMI. Increased PM2.5, PM10 and CO levels are related to increased AMI admissions.

Clinical and procedural predictors of no-reflow in patients with acute myocardial infarction after primary percutaneous coronary intervention.

BACKGROUND: The treatment of acute myocardial infarction (AMI) is thought to restore antegrade blood flow in the infarct-related artery (IRA) and minimize ischemic damage to the myocardium as soon as possible. The present study aimed to identify possible clinical predictors for no-reflow in patients with AMI after primary percutaneous coronary intervention (PCI). METHODS: A total of 312 consecutive patients with AMI who had been treated from January 2008 to December 2010 at the Cardiology Department of East Hospital, Tongji University School of Medicine were enrolled in this study. Inclusion criteria were: (i) patients underwent successfully primary PCI within 12 hours after the appearance of symptoms; or (ii) patients with ischemic chest pain for more than 12 hours after a successful primary PCI within 24 hours after appearance of symptoms. Exculsion criteria were: (i) coronary artery spasm; (ii) diameter stenosis of the culprit lesion was <50% and coronary blood flow was normal; (iii) patients with severe left main coronary or multivessel disease, who had to require emergency revascularization. According to thrombolysis in myocardial infarction (TIMI), the patients were divided into a reflow group and a no-reflow group. The clinical data, angiography findings and surgical data were compared between the two groups. Univariate and multivariate logistic regressions were used to determine the predictors for no-reflow. RESULTS: Fifty-four (17.3%) of the patients developed NR phenomenon after primary PCI. Univariate analysis showed that age, time from onset to reperfusion, systolic blood pressure (SBP) on admission, Killip class of myocardial infarction, intra-aortic balloon pump (IABP) use before primary PCI, TIMI flow grade before primary PCI, type of occlusion, thrombus burden on baseline angiography, target lesion length, reference luminal diameter and method of reperfusion were correlated with no-reflow (P<0.05 for all). Multiple logistic regression analysis identified that age >65 years [OR=1.470, 95% confidence interval (CI) 1.460-1.490, P=0.007], long time from onset to reperfusion >6 hours (OR=1.270, 95%CI 1.160-1.400, P=0.001), low SBP on admission <100 mmHg (OR=1.910, 95%CI 1.018-3.896, P=0.004), IABP use before PCI (OR= 1.949, 95%CI 1.168-3.253, P=0.011), low (≤1) TIMI flow grade before primary PCI (OR=1.100, 95%CI 1.080-1.250, P<0.001), high thrombus burden (OR=1.600, 95%CI 1.470-2.760, P=0.030), and long target lesion (OR=1.948, 95%CI 1.908-1.990, P=0.019) on angiography were independent predictors of no-reflow. CONCLUSION: The occurrence of no-reflow after primary PCI for acute myocardial infarction can predict clinical, angiographic and procedural features.

Modifying clopidogrel maintenance doses according to vasodilator-stimulated phosphoprotein phosphorylation index improves clinical outcome in patients with clopidogrel resistance.

BACKGROUND: Despite dual antiplatelet therapy, the rate of major adverse cardiovascular events (MACE) after percutaneous coronary intervention (PCI) remains high. Ex vivo tests of clopidogrel resistance can predict MACE after PCI. The purpose of this study is to evaluate the clinical impact of adjusting phosphorylation analysis in patients with clopidogrel resistance undergoing PCI. HYPOTHESIS: We hypothesized that VASP-guided clopidogrel maintenance doses, compared to fixed doses, improved clinical outcome. METHODS: This monocentric, prospective, randomized study was performed on 306 patients undergoing PCI. Patients were randomized to a control group (n = 156) and to a vasodilator-stimulated phosphoprotein (VASP)-guided group (n = 150). In the VASP-guided group, patients received adjusted maintenance doses of clopidogrel to obtain platelet reactivity index (PRI) of <50% during 1 year after PCI. The primary endpoint was the rate of MACE. The secondary endpoints were major and minor bleeding. RESULTS: All patients completed the PCI procedure and 298 patients completed follow-up. The control and VASP-guided groups had similar demographic, clinical, and angiographic characteristics. In the VASP-guided group, PRI was significantly decreased (from 72.1% ± 11.4% to 27.7% ± 8.4%; P = 0.001) in 128 patients (87.1% of all participants). During the 1-year follow-up, 14 MACEs were recorded in the VASP-guided group and 30 MACEs were recorded in the control group (9.3% vs 20.4%, respectively; P = 0.008). There was no difference in the rate of major and minor bleeding in the VASP-guided group compared with the control group (12.9% vs 16.6%; P = 0.06). CONCLUSIONS: Modifying clopidogrel maintenance doses according to platelet reactivity monitoring decreases the rate of MACE after PCI without increasing bleeding in patients with clopidogrel resistance during 1-year follow-up.

A novel mutation of the beta myosin heavy chain gene responsible for familial hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disorder and shows high variability in genetic heterogeneity and phenotypic characteristics. The genetic etiology responsible for HCM in many individuals remains unclear. OBJECTIVE: This instigation was sought to identify novel genetic determinants for familial hypertrophic cardiomyopathy. METHODS: Six unrelated Chinese families with HCM were studied. For each of the 13 established HCM-susceptibility genes, 3 to 5 microsatellite markers were selected to perform genotyping and haplotype analysis. The linked genes were sequenced. RESULTS: Haplotype analyses on candidate genetic loci revealed cosegregation of the gene beta-myosin heavy chain (MYH7) with HCM in a single family. A novel double heterozygous missense mutation of Ala26Val plus Arg719Trp in MYH7 was subsequently identified by sequencing in this family and was associated with a severe phenotype of HCM. CONCLUSION: The novel double mutation of Ala26Val plus Arg719Trp in MYH7 identified in a Chinese family highlights the remarkable genetic heterogeneity of HCM, which provides important information for genetic counseling, accurate diagnosis, prognostic evaluation, and appropriate clinical management.

[Comparison of coronary plaque composition between patients with acute coronary syndrome and stable coronary artery disease].

OBJECTIVE: The purpose of the present study was to compare the plaque composition between patients with acute coronary syndrome (ACS) and stable coronary artery disease (SCAD) by intravascular ultrasound virtual histological analysis. METHODS: Two hundred and ten patients were divided into ACS group (n = 131, 188 diseased vessels) and SCAD group (n = 79, 158 diseased vessels). A total of 346 de novo lesions with > 50% stenosis in native coronary arteries with diameters > 2.5 mm were studied with intravascular ultrasonography. Geometric and compositional data were obtained using intravascular ultrasound virtual histology software. RESULTS: There were no significant differences in overall lesions for fibrous (51.2% +/- 12.5% vs. 52.6% +/- 9.6%), fibrolipidic (11.3% +/- 10.6% vs. 12.9% +/- 9.4%), calcium (15.1% +/- 8.9% vs. 20.5% +/- 12.5%) or necrotic core (23.1% +/- 9.8% vs. 20.4% +/- 6.8%, all P > 0.05) components between ACS and SCAD patients. Culprit lesions for fibrous (49.1% +/- 11.2% vs. 50.3% +/- 9.7%), fibrolipidic (10.2% +/- 9.5% vs. 12.7% +/- 9.5%), calcium (15.4% +/- 8.9% vs. 17.4% +/- 24.8%), or necrotic core (24.0% +/- 11.5% vs. 19.7% +/- 5.3%, all P > 0.05) components were also similar between ACS and SCAD patients. High density lipoprotein-cholesterol (HDL) levels > 1.04 mmol/L was associated with more fibrolipidic (15.6% +/- 9.6% vs. 7.4% +/- 5.9%) and less necrotic core (19.4% +/- 8.6% vs. 28.6% +/- 11.2%, all P < 0.05 vs. patients with HDL < or = 1.04 mmol/L) components in ACS patients. CONCLUSION: Coronary plaque composition was similar between ACS and SCAD patients.

Comparison of coronary plaque composition among patients with acute coronary syndrome and stable coronary artery disease.

BACKGROUND: The identification of vulnerable plaques before rupture is an important clinical goal. The purpose of the present study was to assess the difference in plaque composition among patients with acute coronary syndrome (ACS) and stable coronary artery disease (SCAD) by intravascular ultrasound virtual histologic analysis. METHODS: One hundred and thirty-nine patients were divided into ACS group and SCAD group according to clinical presentation. A total of 229 de novo lesions with >50% stenosis in native coronary arteries with diameters >2.5 mm were studied with intravascular ultrasonography. Geometric and compositional data were obtained using intravascular ultrasound virtual histology software. RESULTS: There were no significant differences in overall lesions for fibrous ((52.0+/-11.9)% vs (54.3+/-8.5)%, P>0.05), fibrolipidic ((12.3+/-10.1)% vs (13.8+/-9.5)%, P > 0.05), calcium ((14.0+/-9.1)% vs (19.3+/-13.1)%, P>0.05), or necrotic core ((22.0+/-11.1)% vs (19.7 +/- 5.4)%, P > 0.05) percentages in ACS and SCAD patients, respectively. There were also no significant differences in culprit lesions for fibrous ((46.4+/-12.0)% vs (53.6+/-8.8)%, P>0.05), fibrolipidic ((9.1+/-9.0)% vs (12.9+/-9.7)%, P>0.05), calcium ((16.6+/-9.7)% vs (21.8+/-26.3)%, P>0.05), or necrotic core ((28.0+/-12.6)% vs (20.6+/-5.2)%, P>0.05) percentages in ACS and SCAD patients, respectively. High density lipoprotein-cholesterol levels >1.04 mmol/L were associated with more fibrolipidic ((14.5+/-10.4)% vs (7.1+/-6.5)%, P<0.05) and less necrotic core ((20.6+/-9.7)% vs (27.9+/-12.6)%, P<0.05) percentages in the cohort with ACS. CONCLUSIONS: In this study, coronary plaque composition assessed by intravascular ultrasound virtual histologic analysis was not significantly different between ACS and SCAD patients. The anatomic relationship of the specific plaque components to the lumen of the vessel was more important than the quantitative information of plaque composition for plaque stability.