Elevated lipoprotein-associated phospholipase A2 is associated with progression of nonculprit lesions after percutaneous coronary intervention.

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an enzyme that hydrolyzes oxidized phospholipids to generate bioactive proatherogenic products. Nonculprit lesions have been assumed to contribute to the pathogenesis of recurrent acute coronary syndrome (ACS). The role of LP-PLA2 in the progression of nonculprit coronary lesions after successful percutaneous coronary intervention (PCI) remains unclear. Our study included 123 patients with ACS who underwent initial PCI and a long-term follow-up (mean interval, one year) with coronary angiography. Among them, 19 patients were diagnosed as the progression of nonculprit lesions, based on the presence of at least one of the following factors: (1) ≥ 10% reduction in the diameter of a preexisting ≥ 50% stenosis; (2) ≥ 30% reduction in the diameter of a < 50% stenosis; and (3) early-onset stenosis with ≥ 30% reduction in the diameter of a segment that was normal on the primary angiogram. Blood sampling was drawn from all patients at 12-14 hours after PCI. The ACS patients with progression had higher total cholesterol (4.47 ± 1.02 mmol/L vs. 3.59 ± 0.57 mmol/L, P < 0.05), higher levels of Lp-PLA2 activity (14.39 ± 6.13 nmol/min/ml vs. 8.86 ± 3.14 nmol/min/ml, P < 0.001) and a higher proportion of multi-vessel disease than those without progression. Multivariate logistic regression analysis showed that Lp-PLA2 activity (ß = 0.024, P = 0.005) was an independent predictor for rapid progression of nonculprit coronary lesions. In conclusion, elevated Lp-PLA2 activity is associated with rapid progression of nonculprit coronary lesions in ACS patients who underwent PCI.

An integrative view on the carotid artery alterations in metabolic syndrome.

BACKGROUNDS: Metabolic syndrome (MetS) is a multiple risk factor paradigm widely considered in risk management. We aimed to investigate carotid artery alterations in MetS and the underlying risk factors. MATERIALS AND METHODS: A total of 400 Chinese subjects were recruited, divided into control (n = 200) and MetS (n = 200) groups. Clinical and laboratory characteristics were collected. All subjects underwent carotid ultrasonography. RESULTS: Cardiovascular risk profiles were worse in the MetS than control group (all P < 0.05). After adjusting for MetS and age, the MetS group showed significantly increased mean intima-media thickness (IMT(mean)) and significantly impaired carotid elastic properties (all P < 0.05), as compared to control group. Waist circumference (WC) was positively correlated with IMT(mean) (r = 0.130, P = 0.038), systolic carotid diameter (r = 0.139, P = 0.026) and diastolic carotid diameter (r = 0.168, P = 0.007). systolic blood pressure (SBP) and diastolic blood pressure were positively correlated with IMT(mean) (r = 0.201, P = 0.004; r = 0.168, P = 0.008, respectively), but negatively with arterial compliance coefficient (r = -0.421, P < 0.001; r = -0.230, P < 0.001, respectively). Serum level of high-density lipoprotein (HDL) negatively correlated with IMT(mean) (r = -0.195, P = 0.002). Plaque index was positively correlated with fasting blood glucose (r = 0.205, P = 0.001) after adjusting for the other risk factors. Significantly impaired carotid elastic properties (all P < 0.05) independently correlated with IMT(mean) . Furthermore, age (ß = 0.255, P < 0.001), SBP (ß = 0.224, P < 0.001), WC (ß = 0.202, P < 0.001) and high-density lipoprotein cholesterol (HDL-C) (ß = -0.163, P = 0.001) were independently associated with IMT(mean). CONCLUSION: Carotid alterations consequent upon MetS ultimately developed subclinical and clinical atherosclerosis, the underlying risk factors for which were abdominal obesity, hypertension, ageing and low level of HDL-C.

Plasma lipoprotein-associated phospholipase A2 in patients with metabolic syndrome and carotid atherosclerosis.

BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a recently identified and potentially useful plasma biomarker for cardiovascular and atherosclerotic diseases. However, the correlation between the Lp-PLA2 activity and carotid atherosclerosis remains poorly investigated in patients with metabolic syndrome (MetS). The present study aimed to evaluate the potential role of Lp-PLA2 as a comprehensive marker of metabolic syndrome in individuals with and without carotid atherosclerosis. METHODS: We documented 118 consecutive patients with MetS and 70 age- and sex-matched healthy subjects served as controls. The patients were further divided into two groups: 39 with carotid plaques and 79 without carotid plaques to elucidate the influence of Lp-PLA2 on carotid atherosclerosis. The plasma Lp-PLA2 activity was measured by using ELISA method and carotid intimal-media thickness (IMT) was performed by ultrasound in all participants. RESULTS: Lp-PLA2 activity was significantly increased in MetS subgroups when compared with controls, and was higher in patients with carotid plaques than those without plaques (P < 0.05). Furthermore, we found that significant difference in Lp-PLA2 was obtained between patients with three and four disorders of metabolic syndrome (P < 0.01). Age (ß = 0.183, P = 0.029), LDL-cholesterol (ß = 0.401, P = 0.000) and waist-hip ratio (ß = 0.410, P = 0.000) emerged as significant and independent determinants of Lp-PLA2 activity. Multiple stepwise regression analysis revealed that LDL-cholesterol (ß = 0.309, P = 0.000), systolic blood pressure (ß = 0.322, P = 0.002) and age (ß = 0.235, P = 0.007) significantly correlated with max IMT, and Lp-PLA2 was not an independent predictor for carotid IMT. CONCLUSIONS: Lp-PLA2 may be a modulating factor for carotid IMT via age and LDL-cholesterol, not independent predictor in the pathophysiological process of carotid atherosclerosis in patients with MetS.

Expression of STAMP2 in monocytes associates with cardiovascular alterations.

BACKGROUND: Metabolic and inflammatory pathways crosstalk at many levels. In this study, we aimed to investigate the expression of six-transmembrane protein of prostate 2 (STAMP2) in macrophages and tried to search for the association between the decreased STAMP2 expression, if any, and carotid atherosclerosis as well as cardiac adaptations. MATERIALS AND METHODS: A total of 97 unrelated Chinese subjects were recruited including 48 subjects with metabolic syndrome (MetS) and 49 controls. Clinical and biochemical characteristics were collected from subjects, with quantification of STAMP2 in monocyte/macrophages. All subjects underwent ultrasonography. RESULTS: STAMP2 expression in macrophages was significantly decreased in MetS as compared with the control group (10.25 +/- 9.20 vs. 15.20 +/- 9.18, P = 0.009), especially in women patients. Partial correlation analysis showed that STAMP2 expression in macrophages correlated with BMI (r = -0.375, P = 0.045), age (r = 0.414, P = 0.026) and HDL (r = 0.377, P = 0.044) after controlling for systolic blood pressure (SBP). Furthermore, STAMP2 expression was correlated with PI (r = -0.454, P = 0.013), LVEF (r = -0.503, P = 0.005), LA-ESR (r = -0.424, P = 0.022), LA-S (r = 0.469, P = 0.010) and mitral E/A ratio (r = 0.492, P = 0.005) after controlling for SBP. Still, in multivariable analysis, STAMP2 expression was independently associated with IMT(mean), PI and mitral E/A ratio. CONCLUSIONS: In MetS patients, especially women patients, STAMP2 expression was down-regulated in peripheral blood mononuclear cell, which was correlated with carotid atherosclerosis and cardiac adaptation.

Impaired elastic properties of the aorta in fat-fed, streptozotocin-treated rats. Vascular remodeling in diabetic arteries.

BACKGROUND: Vascular complications associated with diabetes are the major cause for the increased morbidity and mortality in diabetic patients. However, the progression of vascular complications in diabetes is not well understood. We aimed to investigate the biomechanical and biochemical changes associated with vascular dysfunction in diabetic rats. METHODS: Male Wistar rats were randomly divided into two groups: normal control (n = 8) and fat-fed, streptozotocin-treated diabetic rats (n = 11). After 16 weeks, Peterson's modulus of elasticity (Ep) and cross-sectional distensibility (CD) were calculated and compared between the two groups. Aortas were harvested from rats for histopathological and electron-microscopic analysis. RESULTS: Collagenous fibers were scattered in the extracellular matrix and invaded the elastic lamina in the aortas of diabetic rats, suggesting a significant accumulation of collagen in diabetic vessels. Compared with normal rats, diabetic rats showed significantly reduced aortic distensibility (CD: 0.10 +/- 0.04 vs. 0.17 +/- 0.08 kPa(-1), p = 0.033) and an increased aortic stiffness index (Ep: 0.25 +/- 0.13 vs. 0.15 +/- 0.05 x 10(6) dyn/cm(2), p = 0.045). Ep was positively and CD negatively correlated with glucose and collagen in diabetic rats. CONCLUSIONS: In diabetic rats, elastic properties of the aorta are impaired, being closely related to hyperglycemia-induced vascular wall remodeling.

Predictive value of fasting blood glucose for serious coronary atherosclerosis in non-diabetic patients.

OBJECTIVE: To determine if high fasting blood glucose (FBG) level is an independent predictor of serious coronary lesions in patients with coronary artery disease (CAD). METHODS: We enrolled 64 patients who had symptoms of chest discomfort and who underwent coronary angiography. FBG was determined from blood samples and the extent of coronary artery lesions was analyzed according to Gensini score. We examined the relationships among diabetes, FBG, and coronary artery severity. RESULTS: Diabetes and FBG were significantly and positively related to Gensini score. Diabetes, but not FBG, was independently correlated with the occurrence of a Gensini score >41. However, FBG was significantly associated with Gensini score >41 in non-diabetic patients. CONCLUSION: Hyperglycemia is an independent predictor of severe CAD in non-diabetic patients. Clinicians should be aware of this and should carry out appropriate early interventions.

Impaired left ventricular synchronicity in hypertensive patients with ventricular hypertrophy.

OBJECTIVES: The influence of left ventricular hypertrophy (LVH) on left ventricular synchronicity, and the prevalence of left ventricular dyssynchrony in hypertensive patients with LVH are unknown. The purpose of this study was to determine the influence of LVH on left ventricular synchronicity in hypertensive subjects. METHOD: Tissue Doppler imaging (TDI) was performed in 115 hypertensive and 30 control individuals. Hypertensive patients were divided into a LVH group and a non-LVH group according to the left ventricular mass index (LVMI). Diastolic and systolic asynchrony was determined by measuring the maximal differences in time to peak myocardial systolic contraction (Ts-max) and early diastolic relaxation (Te-max) between any two of the left ventricular segments and the standard deviation of time to peak myocardial systolic contraction and early diastolic relaxation of all 12 segments. RESULTS: Ts-max was greater in both the non-LVH and LVH groups than in controls, (96.68 +/- 26.21 versus 79.30 +/- 25.19 versus 53.20 +/- 15.24 ms, both P < 0.001) and in the LVH group than in the non-LVH group (96.68 +/- 26.21 versus 79.30 +/- 25.19 ms, P < 0.01). Te-max was prolonged in both patient groups, being most advance in the LVH group (67.39 +/- 11.01 versus 57.18 +/- 11.42 versus 46.72 +/- 13.24 ms, both P < 0.001 versus control group and P < 0.001 versus non-LVH group). LVH patients had shown a greater prevalence of both systolic and diastolic asynchrony than non-LVH patients. A Ts-max value greater than 88 ms had 68% sensitivity and 71% specificity for detecting hypertensive patients with LVH. CONCLUSION: Left ventricular systolic synchronicity was impaired in hypertensive patients with LVH. TDI was shown to be useful for the detection of myocardial abnormalities in such patients.

Increased serum visfatin in patients with metabolic syndrome and carotid atherosclerosis.

OBJECTIVE: Visfatin is a newly identified adipocytokine and recent studies indicated that visfatin may have potential proinflammatory effect. However, its pathophysiological role in the metabolic syndrome (MetS) is not fully understood. In this study we investigated whether serum visfatin levels is altered in patients with the MetS, and compared the levels of visfatin between patients with and without carotid plaques. DESIGN AND METHOD: A total of 139 patients with MetS and 105 controls were included. The patients were further divided into two groups: 40 with carotid plaques and 99 without carotid plaques. Serum visfatin was measured by using enzyme immunoassay method and carotid intimal-media thickness (IMT) was measured by ultrasound in all subjects. RESULTS: Serum visfatin was elevated in both MetS patients with and without carotid plaques compared to controls (log visfatin: 1.14 +/- 0.14 vs. 0.99 +/- 0.17 ng/ml vs. 0.93 +/- 0.23 ng/ml, P < 0.001 and P < 0.05 vs. control group, respectively), and in patients with carotid plaques more than in patients without carotid plaques (P < 0.001). Multiple stepwise regression analysis revealed that only LDL-cholesterol correlated with visfatin, and visfatin independently correlated with max IMT in the patients with MetS. A log visfatin > 1.08 ng/ml had 70% sensitivity and 67% specificity for detecting patients with carotid plaques. CONCLUSIONS/INTERPRETATION: Our results showed that serum visfatin was increased in patients with MetS, especially in those with carotid plaques. Visfatin may be an inflammatory marker of MetS.

Felodipine attenuates vascular inflammation in a fructose-induced rat model of metabolic syndrome via the inhibition of NF-kappaB activation.

AIM: Metabolic syndrome is associated with an increased incidence of atherosclerosis. Clinical studies have shown that calcium channel blockers (CCB) inhibit the progression of atherosclerosis. However, the underlying mechanism is unclear. We investigated the inhibitory effect of felodipine on adhesion molecular expression and macrophage infiltration in the aorta of high fructose-fed rats (FFR). METHODS: Male Wistar rats were given 10% fructose in drinking water. After 32 weeks of high fructose feeding, they were treated with felodipine (5 mg x kg(-1) x d(-1)) for 6 weeks. The control rats were given a normal diet and water. The aortic expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) and the infiltration of macrophages were measured by real-time RT-PCR and/or immunohistochemistry. NF-kappaB activity was measured by electrophoretic mobility shift assay (EMSA). RESULTS: After 32 weeks of high fructose feeding, FFR displayed increased body weight, systolic blood pressure (SBP), serum insulin, and triglycerides when compared with the control rats. The aortic expressions of ICAM-1 and VCAM-1 were significantly increased in FFR than in the control rats and accompanied by the increased activity of NF-kappaB. FFR also showed significantly increased CD68- positive macrophages in the aortic wall. After treatment with felodipine, SBP, serum insulin, and the homeostasis model assessment decreased significantly. In addition to reducing ICAM-1 and VCAM-1, felodipine decreased macrophages in the aortic wall. EMSA revealed that felodipine inhibited NF-kappaB activation in FFR. CONCLUSION: Felodipine inhibited vessel wall inflammation. The inhibition of NF-kappaB may be involved in the modulation of vascular inflammatory response by CCB in metabolic syndrome.

Possible beneficial effect of olmesartan medoxomil on left atrial function in patients with hypertension : noninvasive assessment by acoustic quantification.

BACKGROUND AND OBJECTIVE: Hypertension alters the diastolic properties of the left ventricle and results in deterioration in the structure and function of the left atrium. We aimed to evaluate whether olmesartan medoxomil has an effect on left atrial function in hypertensive patients. METHODS: Fifty hypertensive patients and 20 controls were included in the study. Hypertensive patients were treated with olmesartan medoxomil for 8 weeks. Before and after treatment, study participants were examined by acoustic quantification and tissue Doppler imaging. Left atrial reservoir function was assessed by end-diastolic volume (EDV), end-systolic volume (ESV), reservoir volume (RV) and peak filling rate (PFR). Left atrial booster pump function was assessed by atrial emptying volume (AEV), atrial emptying fraction (AEF) and peak atrial emptying rate (PAER). Left atrial conduit function was assessed by rapid emptying volume (REV), rapid emptying fraction (REF), REV/AEV ratio, and the ratio of peak rapid emptying rate and PAER (PRER/PAER). RESULTS: Atrial RV and PFR were significantly increased in hypertensive subjects (48.30 +/- 19.28 mL vs 34.35 +/- 14.26 mL, p < 0.001; 267.26 +/- 126.52 mL/s vs 206.81 +/- 107.17 mL/s, p < 0.05) compared with controls, while the REV/AEV ratio was decreased in hypertensive patients compared with controls (2.86 +/- 0.85 vs 3.69 +/- 2.13, p < 0.001). After therapy with olmesartan medoxomil, atrial RV (48.30 +/- 19.28 mL vs 40.50 +/- 17.59 mL) and PFR decreased (267.26 +/- 126.52 mL/s vs 220.40 +/- 108.56 mL/s, p < 0.05) and the REV/AEV ratio increased (2.86 +/- 0.85 vs 3.14 +/- 0.43, p < 0.05) in hypertensive patients. CONCLUSION: Our novel findings indicate that left atrial function is impaired in hypertensive patients, and that olmesartan medoxomil can improve left atrial function in this context. Our study also showed that acoustic quantification is useful for non-invasive evaluation of the benefits of treatment on left atrial function.

Ulinastatin attenuates diabetes-induced cardiac dysfunction by the inhibition of inflammation and apoptosis.

Ulinastatin exhibits anti-inflammatory activity and protects the heart from ischemia/reperfusion injury. However, whether ulinastatin has a protective effect in diabetic cardiomyopathy is yet to be elucidated. The aim of the present study was to investigate the protective effects of ulinastatin against diabetic cardiomyopathy and its underlying mechanisms. A C57/BL6J mice model of diabetic cardiomyopathy was used and mice were randomly assigned to three groups: Control group, diabetes mellitus (DM) group and DM + ulinastatin treatment group. Cardiac function was assessed using echocardiography and the level of inflammatory cytokine high mobility group box 1 (HMGB1) expression was measured using histopathological examination and reverse transcription-quantitative polymerase chain reaction. The levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 were measured using western blotting and ELISA. The apoptosis rate in the myocardium was assessed by TUNEL assay. Caspase-3 activation, expression of B-cell lymphoma 2 (Bcl-2) and Bcl-2 associated × (Bax) were measured using western blotting, as was the activity of the mitogen activated protein kinase (MAPK) signaling pathway. The results indicated that ulinastatin significantly improved cardiac function in mice with DM. Ulinastatin treatment significantly downregulated HMGB1, TNF-α and IL-6 expression (P<0.05) and significantly reduced the percentage of apoptotic cardiomyocytes (P<0.05) via reduction of caspase-3 activation and the ratio of Bax/Bcl-2 in diabetic hearts (P<0.05). In addition, ulinastatin attenuated the activation of the MAPK signaling pathway. In conclusion, ulinastatin had a protective effect against DM-induced cardiac dysfunction in a mouse model. This protective effect may be associated with the anti-inflammatory and anti-apoptotic abilities of ulinastatin via the MAPK signaling pathway.

[Mechanism of reversion of myocardial interstitial fibrosis in diabetic cardiomyopathy by valsartan].

OBJECTIVE: To investigate the mechanism of reversion of myocardial interstitial fibrosis in diabetic cardiomyopathy (DCM) by valsartan. METHODS: Forty male wistar rats were randomly divided into 3 groups: DCM group, n = 16, fed with high-fat diet for 4 weeks and injected intraperitoneally with streptozocin (STZ) once to induce hyperglycemia so as to construct a DCM model, and then perfused into the stomach with normal saline; valsartan group, n = 16, to be constructed into DCM model and then perfused into the stomach with valsartan once daily; and control group (n = 8, fed with normal food and perfused into the stomach with normal saline. Four weeks after feeding (i.e., before injection of STZ), 1 week after STZ injection, and by the end of experiment after 12-hour fasting samples of venous blood were collected to detect the contents of triglyceride and fasting blood-glucose and insulin; by the end of experiment miniature cardiac catheter was inserted into the left ventricle to conduct hemodynamic examination. Then myocardium tissues were collected, collagen content was detected by Masson staining, real-time RT-PCR was used to detect the mRNA expression of thrombospondin (TSP)-1 and tumor growth factor (TGF)-beta(1) mRNA, expression, and Western blotting was used to detect the protein expression of TSP-1, active TGF-beta(1) (A-TGF-beta(1)) and latent TGF-beta(1) (L-TGF-beta(1)). RESULTS: By the end of the experiment, the body weights, and insulin sensitivity index were significantly lower and fasting blood-glucose, and serum triglyceride and cholesterol were significantly higher in the DCM group and valsartan group in comparison with those in the control group (all P < 0.01), however, there was no significant differences in fasting insulin among these 3 groups. The values of left ventricular systolic pressure (LVSP) and +/- dp/dt(max) were significantly lower and left ventricular end diastolic pressure were significantly higher in the DCM group in comparison with the control group (all P < 0.01). The LVSP and -dp/dt(max) were significantly higher and LVEDP was significantly lower in the valsartan group than in the DCM group (all P < 0.05). The LVEDP was significantly higher and -dp/dt(max) was significantly lower in the valsartan group than in the control group. Electron microscopy showed the distribution of a great amount of collagen in the myocardial interstitial tissue. The collagen content of the DCM group was 17 +/- 3, significantly higher than that of the control group (11 +/- 3, P < 0.05), and the collagen content of the valsartan group was 13 +/- 3, significantly lower than that of the DCM group (P < 0.05). The mRNA expression of TSP-1 and that of TGF-beta(1) were significant higher in the DCM group than in the control group (both P < 0.05), and were significantly lower in the valsartan group than in the DCM group (both P < 0.05); however, the TGF-beta(1) mRNA expression in the valsartan group was significantly higher in the valsartan group than in the control group (P < 0.05). The values of protein expression of TSP-1, A-TGF-beta(1) and L-TGF-beta(1) were all significantly higher in the DCM group than in the control group (all P < 0.05), and the values of protein expression of TSP-1 and A-TGF-beta(1) in the valsartan group were both significantly lower than those in the DCM group (both P < 0.05), however, there was no significant difference in the protein expression of L-TGF-beta(1) between the valsartan group and DCM group. CONCLUSION: Valsartan amelioorates myocardial interstitial fibrosis in DCM via TSP-1/TGF-beta(1) signaling pathway.

[The role of glucose/TSP-1/TGFbeta1 signal pathways in diabetic cardiomyopathy].

OBJECTIVE: Hyperglycemia could upregulate transforming growth factor-beta (TGFbeta(1)) via thrombospondin (TSP-1) and induce fibrotic renal disease in the rat in vivo and myocardial fibrosis was related to cardiac dysfunction in diabetic patients. We explored the role of glucose/TSP-1/TGFbeta(1) signal pathways in the development of diabetic cardiomyopathy (DCM). METHODS: Male Wistar rats were fed with high cholesterol diet for 17 weeks, streptozocin (30 mg/kg, i.p) was given at the 28th day, rats with fasting blood glucose > or = 11.1 mmol/L by the end of the 5th week were assigned to DCM group (n = 11). Control rats (n = 8) were fed with regular chow. Fasting blood glucose (FBG) was monitored throughout the study. After hemodynamic measurements by the end of the study, myocardial collagen content was quantified in Masson-stained samples and the mRNA expressions of TSP-1 and TGFbeta(1) were detected by quantification real-time RT-PCR. The protein levels of TSP-1, active and latent TGFbeta(1) were detected by Western blot. RESULTS: Compared with control group, cardiac function was decreased as shown by significantly reduced left ventricular systolic pressure, dp/dt(max) and dp/dt(min), while the myocardial collagen content was significantly increased in the DCM group (11.01 +/- 3.05 vs. 16.92 +/- 3.18, P < 0.01). The myocardial mRNA expressions of TSP-1, TGFbeta(1) and protein expressions of TSP-1, active and latent TGFbeta(1) in the DCM group were also significantly higher than those of the control group. Moreover, myocardial collagen was positively correlated to FBG (r = 0.746, P < 0.01); mRNA expressions of TSP-1 and TGFbeta(1), protein expressions of TSP-1 and active TGFbeta(1) were positively correlated to FBG and myocardial collagen (P < 0.05). However, there were no correlations between the protein expression of latent TGFbeta(1) and FBG and myocardial collagen. CONCLUSION: The pathway of glucose/TSP-1/TGFbeta(1) might play an important role in myocardial interstitial fibrosis of DCM. It may be the basis of novel therapeutic approaches for ameliorating DCM.

Strain/strain rate imaging of impaired left atrial function in patients with metabolic syndrome.

Left ventricular (LV) dysfunction has been demonstrated in patients with metabolic syndrome (MetS). However, alterations in left atrial (LA) function in MetS are unknown. We aimed to use strain/strain rate (SR) imaging to investigate the effect of MetS on LA function. A total of 177 MetS patients and 156 normal subjects underwent echocardiography. Strain and SR tissue Doppler imaging values were used to evaluate LA function. Partial correlation and multiple stepwise regression analyses were used to determine the risk factors for impaired LA function. Compared with the controls, the MetS patients showed significantly lower levels of mean strain, mean peak systolic SR and mean peak early diastolic SR (P<0.001 for all), with no difference in the mean peak late diastolic SR. Central obesity, hypertension, dyslipidemia and LV diastolic abnormality were independent risk factors for impaired LA function. LA function was impaired in patients with MetS as a result of metabolic disturbance and LV diastolic abnormality. SR imaging is reliable in assessing LA function in MetS patients.

Tribbles homolog 3 is induced by high glucose and associated with apoptosis in human endothelial cells.

Tribbles homolog 3 (TRIB3) is an intracellular kinase-like molecule that modifies cellular survival and metabolism. The present study aimed to investigate the function of TRIB3 regulation in the process of high glucose-induced apoptosis in endothelial cells, with the aim of identifying a novel intervention target for the prevention and treatment of diabetes mellitus. Human umbilical vein endothelial cells (HUVECs) grown in medium with various concentrations of glucose (5.5, 10, 20, 30 and 40 mmol/l) were assessed for mRNA expression of TRIB1, TRIB2 and TRIB3 using reverse transcription quantitative polymerase chain reaction. In addition, protein expression of TRIB3 was examined using western blot analysis. Immunofluorescence staining was performed in order to determine the distribution and localization of TRIB3 in HUVECs. Furthermore, cells grown in normal (5.5 mmol/l) or high glucose (HG; 30 mmol/l) medium were subjected to TRIB3 inhibition through small interfering (si)RNA knockdown. These cells were then examined in order to determine whether TRIB3 upregulation was associated with endothelial cell apoptosis. HUVECs treated with 30 and 40 mmol/l glucose for 48 h and 72 h showed significantly lower survival rates compared with those treated with normal glucose levels. In addition, slight but not significant increases in TRIB1 and TRIB2 mRNA expression were observed in HUVECs incubated with various concentrations of glucose for different durations. By contrast, TRIB3 mRNA expression was increased 7.2-fold following incubation with HG. Western blot analysis revealed a 5.44-fold increase in TRIB3 protein levels in cells grown in HG medium for 24 h compared with those grown in normal medium. Immunostaining assays revealed a markedly higher and well-defined nucleolar fluorescence intensity for TRIB3 expression at 24 h in HG medium compared with that of the control group. Furthermore, the apoptotic rate of HG-treated TRIB3 siRNA-transfected HUVECs was significantly increased compared with that of those transfected with control siRNA In conclusion, the results of the present study suggested that TRIB3 was associated with high glucose-induced HUVECs apoptosis, which was attenuated following transfection with TRIB3 siRNA.

The application of vWF/ADAMTS13 in essential hypertension.

BACKGROUND: Plasma von Willebrand factor (vWF), a key player in hemostasis and thrombosis, is released from endothelial cells during inflammation. Hypertension, a progressing in chronic inflammation and cardiovascular syndrome with various causes, results in functional and structural changes of heart and arterial vessels. However little information is available on LA changes during hypertension. Left atrial (LA) enlargement is associated with significant cardiovascular morbidity and mortality. The aim of this study was to explore the relationship between LA enlargement and thromboembolic risk in essential hypertensive patients with Af without any signs of clinical thrombotic disease or previous stroke. METHODS: The relationship between Plasma vWF, ADAMTS13 and left atrial diameter (LAD), left atrial volume (LAV), left atrial volume index (LAVi) were evaluated in essential hypertensive group included 105 patients (55 patients with nonvalvular atrial fibrillation (AF) and 50 patients with normal sinus rhythm (NSR)). RESULTS: The study demonstrated that vWF, vWF/ADAMT13, LAD, LAV and LAVi were increased significantly (P < 0.01) but ADAMTS13: Ag was decreased significantly (P < 0.01) in the hypertensive with AF group compared with NSR group. CONCLUSION: vWF/ADAMTS13 were positively correlated with LAD, LAV and LAVi (P < 0.01). Increased vWF and vWF/ADAMTS13 is associated with LAD, LAV and LAVi in essential hypertension. The study suggests it played a positive role of vWF and vWF/ADAMTS13 in the progressing major adverse cardiovascular events (MACE) in essential hypertensive patients with LA enlargement.

IL-18 overexpression promotes vascular inflammation and remodeling in a rat model of metabolic syndrome.

Although considerable evidence implicates the cytokine interlukin-18 (IL-18) in metabolic syndrome (MetS), the direct effect of IL-18 on vascular changes of MetS remains unknown. We investigated the chronic in vivo effect of IL-18 on development of MetS and vascular inflammation and remodeling by overexpressing IL-18 protein in fructose-fed rats (FFR), a model of MetS using intravenous administration of an adenovirus encoding rat IL-18. Increased serum IL-18 and vascular inflammatory response were found in FFR. Overexpression of IL-18 aggravated insulin resistance and enhance vascular inflammation and remodeling, which can be reflected by increased aortic expressions of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) and enhanced infiltration of macrophages and increased aortic wall thickness and wall-to-lumen ratio. Interestingly, the levels of interleukin-1 receptor-associated kinase 1 (IRAK1) and the activity of nucleus factor-kappaB (NF-kappaB) were also significantly increased. Together, these results indicated that chronic elevated IL-18 levels at a supraphsiological concentration aggravated insulin resistance, enhanced vascular inflammation and remodeling, probably by increasing the level of IRAK1 and the activity of NF-kappaB. Targeting expression of IL-18 or its specific downstream mediators may retard the progression of MetS and its complications.

Impaired left ventricular synchronicity in patients with metabolic syndrome, regardless of hypertension.

OBJECTIVE: To assess the left ventricular (LV) diastolic and systolic synchronicity in patients with metabolic syndrome. METHODS: Tissue Doppler echocardiography was performed in 235 individuals (135 with metabolic syndrome and 100 controls). Diastolic and systolic synchronicity was determined by measuring the SD of time to peak myocardial early diastolic relaxation and systolic contraction and the maximal difference in time to peak myocardial early diastolic relaxation and systolic contraction with six basal and six middle LV segments. RESULTS: Compared with controls, patients with metabolic syndrome showed significantly prolonged SD of time to peak myocardial early diastolic relaxation (20.79 +/- 11.29 vs. 16.33 +/- 5.67 ms, P < 0.001) and SD of time to peak myocardial early systolic contraction (24.50 +/- 15.27 vs. 17.27 +/- 5.46 ms, P < 0.001) and prolonged maximal difference in time to peak myocardial early diastolic relaxation (66.76 +/- 40.81 vs. 45.59 +/- 17.78 ms, P < 0.001) and maximal difference in time to peak myocardial early systolic contraction (71.47 +/- 49.19 vs. 47.64 +/- 17.25 ms, P < 0.001) among all the 12 left ventricular segments. Multiple regression analysis revealed waist-to-hip ratio, fasting blood glucose, age and LV mass for height to the power 2.7 as independent predictors of impaired diastolic synchronicity in metabolic syndrome, with age and LV mass for height to the power 2.7 as independent predictors of impaired systolic synchronicity. Subgroup analyses indicated that there was no difference of LV synchronicity between nonhypertensive and hypertensive subgroups in metabolic syndrome patients. CONCLUSION: Patients with metabolic syndrome have impaired LV diastolic and systolic synchronicity. Obesity, hyperglycemia and age play important roles in it, whereas hypertension is not the key factor to cause the impaired synchronicity.

Impaired atrial synchronicity in patients with metabolic syndrome associated with insulin resistance and independent of hypertension.

The risk of developing atrial fibrillation is increased in patients with metabolic syndrome, but atrial conduction properties are uncharacterized in patients who have metabolic syndrome without atrial arrhythmia. We used tissue Doppler imaging to evaluate intra- and interatrial synchronicity in such patients. The imaging was performed in 145 patients with metabolic syndrome and 110 controls. Atrial synchronicity was determined from the intervals between the onset of the P-wave to the onset of the A-wave at the left atrial free wall (P-LA), interatrial septum (P-IAS) and right atrial free wall (P-RA). Intra-atrial synchronicity was defined as the differences between P-IAS and P-RA (RA synchronicity) and between P-LA and P-IAS (LA synchronicity). Interatrial synchronicity was defined as the difference between P-LA and P-RA. P-LA and P-IAS were significantly prolonged in the metabolic syndrome group relative to the control group (P-LA: 64.34+/-13.99 vs. 55.35+/-12.67, P<0.001; P-IAS: 36.49+/-12.39 vs. 31.55+/-11.61, P=0.001), whereas P-RA showed no difference. As a result, this caused impaired intra- and interatrial synchronicity in patients with metabolic syndrome. Stepwise multivariate linear analysis revealed insulin resistance as an independent predictor of impaired intra- and interatrial synchronicity. Subgroup analysis indicated that there was no difference in atrial asynchrony between non-hypertensive and hypertensive subgroups in metabolic syndrome patients. In conclusion, patients with metabolic syndrome without atrial arrhythmia have impaired intra- and interatrial synchronicity. Insulin resistance has an important role in impaired atrial conduction in these patients.

Impaired left ventricular systolic and diastolic function in patients with metabolic syndrome as assessed by strain and strain rate imaging.

The present study aimed to investigate cardiac structural and functional alterations in patients with metabolic syndrome (MS) and to compare those with control subjects. Strain and strain rate (SR) imaging were preformed in 200 patients with MS and 197 normal subjects. The patients were further divided into Group 1 (with three metabolic disorders) and Group 2 (with four metabolic disorders) to elucidate the influence of different metabolic components on left ventricular (LV) functions. LV diastolic and systolic functions were determined by the mean systolic strain, SR-LVs and SR-LVe. There were no differences in LVEF among the three groups. However, the mean systolic strain, SR-LVs and SR-LVe, were significantly decreased in Group 1 and Group2 when compared with control subjects (all P<0.001). The mean systolic strain and SR-LVe were lower in Group 2 than Group 1 (all P<0.05). Stepwise multiple regression analyses revealed that the W-H ratio was an independent predictor of the LV systolic function, whereas W-H ratio, HDL cholesterol and SBP were independent predictors of LV diastolic function. In summary, our results demonstrated that LV systolic and diastolic functions were impaired in patients with metabolic syndrome even if they have normal LVEF. Strain and SR imaging would be a sensitive and feasible method to detect subclinical abnormalities in those populations.