Functional Role and Mechanism of microRNA-28b in Atrial Myocyte in a Persistent Atrial Fibrillation Rat Model.

BACKGROUND Persistent atrial fibrillation has been indicated to be related with microRNA-28b. However, the exact role of microRNA-28b in persistent atrial fibrillation needs to be further elucidated. Therefore, this study aimed to establish a rat model of persistent atrial fibrillation to investigate the level of microRNA-28b in atrial myocytes and to explore the molecular mechanism involved. MATERIAL AND METHODS A persistent atrial fibrillation model was established in rats by using chronic rapid atrial pacing induction. The size of the heart was measured by ultrasonic method. The expression of microRNA-28b in left atrial myocytes was quantified by RT-PCR. Cardiomyocytes were isolated and cultured to detect cell proliferation and apoptosis by MTT and flow cytometry, respectively. The specific inhibitor of ERK signaling pathway, PD98059, was used to further illustrate the role of ERK signaling pathway in the modulation of cardiomyocytes in persistent atrial fibrillation. RESULTS MicroRNA-28b was up-regulated in the experimental rat model with persistent atrial fibrillation. The proliferation of cardiomyocytes was significantly inhibited with potentiated apoptosis. Blockage of the ERK pathway suppressed the microRNA-28b expression and inhibited cell apoptosis. CONCLUSIONS microRNA-28b-induced growth inhibition and cell apoptosis of atrial myocytes was observed in the rat model with persistent atrial fibrillation, via activation of the ERK signaling pathway.

Rutin alleviates diabetic cardiomyopathy in a rat model of type 2 diabetes.

Diabetic cardiomyopathy (DCM), an independent coronary heart disease that develops in diabetic individuals, is characterized by changes in the myocardial structure and function. The aim of the present study was to investigate the protective effect of rutin on DCM in a streptozotocin-induced diabetic rat model. Rutin was orally administrated at a dose of 8 mg/kg body weight. Metabolic profiles, myocardial enzymes and oxidative stress were examined by biochemical tests. The expression levels of cellular proteins associated with apoptosis were measured by western blot analysis, while the levels of inflammatory factors were assessed by immunohistochemical analyses. Rats with DCM exhibited an abnormal metabolic profile, aberrant myocardial enzymes, elevation of oxidative stress markers, increased levels of inflammatory factors and enhanced apoptotic cell death. Notably, rutin was shown to protect and improve myocardial dysfunction, oxidative stress, apoptosis and inflammation in the hearts of the diabetic rats. In conclusion, these results indicated that rutin may have great therapeutic potential in the treatment of DCM, and possibly other cardiovascular disorders, by preventing oxidative stress, inflammation and cell death. However, further detailed studies are required to reveal the exact mechanisms underlying the protective effect of rutin.

Irbesartan ameliorates diabetic cardiomyopathy by regulating protein kinase D and ER stress activation in a type 2 diabetes rat model.

Recent studies demonstrate an important role of protein kinase D (PKD) in the cardiovascular system. However, the potential role of PKD in the pathogenesis of diabetic cardiomyopathy (DCM) remains unclear. Irbesartan has beneficial effects against diabetes-induced heart damage, while the mechanisms were still poorly understood. Our present study was designed to investigate the effects of irbesartan in DCM and whether the cardioprotective effects of irbesartan were mediated by PKD and endoplasmic reticulum (ER) stress. We induced the type 2 diabetic rat model by high fat diet and low dose streptozotocin injection. The characteristics of type 2 DCM were evaluated by metabolic tests, echocardiography and histopathology. 8-weeks administration of irbesartan (15, 30 and 45mg/kg/day) was used to evaluate the effect irbesartan in DCM. Diabetic rats revealed severe metabolic abnormalities, left ventricular dysfunction, myocardial fibrosis and apoptosis. PKD and ER stress were excessive activated in the myocardium of diabetic rats. Furthermore, cardiac fibrosis, apoptosis, diastolic dysfunction and ER stress were all significantly related to PKD activation in diabetic rats. Irbesartan treatment attenuated the activation of PKD and ER stress, which paralleled its cardioprotective effects. Our study suggests that irbesartan could ameliorate cardiac remodeling and dysfunction in type 2 diabetes, and these beneficial effects were associated with its ability to suppress the activation of PKD and ER stress.

A novel PITX2c loss­of­function mutation underlies lone atrial fibrillation.

Atrial fibrillation (AF) is the most common form of sustained cardiac arrhythmia responsible for substantial morbidity and significantly increased mortality rates. A growing body of evidence documents the important role of genetic defects in the pathogenesis of AF. However, AF is a heterogeneous disease and the genetic determinants for AF in an overwhelming majority of patients remain unknown. In the present study, a cohort of 100 unrelated patients with lone AF and a total of 200 unrelated, ethnically matched healthy individuals used as controls, were recruited. The whole coding exons and splice junctions of the pituitary homeobox 2c (PITX2c) gene, which encodes a paired­like homeobox transcription factor required for normal cardiovascular morphogenesis, were sequenced in the 100 patients and 200 control subjects. The causative potential of the identified mutation of PITX2c was predicted by MutationTaster and PolyPhen­2. The functional characteristics of the PITX2c mutation were assayed using a dual­luciferase reporter assay system. Based on the results, a novel heterozygous PITX2c mutation (p.T97A) was identified in a patient with AF. The missense mutation was absent in the 400 reference chromosomes and was automatically predicted to be disease­causing. Multiple alignments of PITX2c protein sequences across species revealed that the altered amino acid was completely conserved evolutionarily. Functional analysis demonstrated that the mutant PITX2c protein was associated with significantly decreased transcriptional activity when compared with its wild­type counterpart. The findings of the present study firstly link the PITX2c loss­of­function mutation to lone AF, and provide novel insight into the molecular mechanisms underlying AF, suggesting the potential implications for the early prophylaxis and allele­specific therapy of this common type of arrhythmia.

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.

Epigallocatechin gallate attenuated the activation of rat cardiac fibroblasts induced by angiotensin II via regulating ß-arrestin1.

BACKGROUND/AIMS: Angiotensin II (AngII) activated cardiac fibroblasts (CFs) predominantly through AngII subtype 1a receptor (AT1aR). This study was carried out to explore the potential inhibitory effects and mechanisms of epigallocatechin gallate (EGCG) on AngII induced rat CFs. METHODS: Viability, proliferation and collagen production of CFs were measured by MTT assay, [3H]-thymidine and [3H]-proline incorporation respectively. ß-arrestin1 (ßarr1), AT1aR and AT1bR mRNA levels were determined by quantitative PCR. AT1R, Gq, ßarr 1/2, phosphorylated kinase C (p-PKC)-delta expressions were detected by western blotting. We blocked ßarr1 expression using ßarr1 small interfering RNA (siRNA). RESULTS: EGCG inhibited the activation of CFs induced by AngII. ßarr1 mRNA level revealed a positive correlation with the viability of CFs. SiRNA targeting ßarr1 blocked the activation of CFs. In vitro, AngII increased ßarr1 mRNA, total and membrane ßarr1 protein expressions, but reduced AT1aR mRNA, global and membrane AT1R, total Gq and cytoplasmic p-PKC-delta levels. Administration of EGCG restored the above abnormalities, whereas Gq levels were not affected. CONCLUSION: Our findings showed that ßarr1 is essential for AngII-mediated activation of CFs. EGCG attenuated CFs activation induced by AngII via regulating ßarr1 and thus, modulating AT1aR mediated signaling.

Valsartan protects against ER stress-induced myocardial apoptosis via CHOP/Puma signaling pathway in streptozotocin-induced diabetic rats.

Recently studies indicated that valsartan could prevent the progression of heart failure caused by diabetic cardiomyopathy (DCM), while the mechanisms were still poorly understood. The present study was designed to investigate whether valsartan could reduce the endoplasmic reticulum (ER) stress and DCM-induced cardiac remodeling. Our data has shown that valsartan can ameliorate ER stress-induced cardiac remodeling and myocardial apoptosis in DCM rats. By using of immunofluorescence and RT-PCR, valsartan has been found to play a protective role via down-regulating the expression of transcriptional induction of C/EBP homologous protein (CHOP) and p53 upregulated modulator of apoptosis (Puma), two crucial factors known to be implicated in the ER stress-induced myocardial apoptosis. And the expression level of Puma was closely related to CHOP. Thus, our experiment strongly suggests that the administration of valsartan can ameliorate the ER stress through blocking the activation of CHOP/Puma signaling pathway, which provides a new insight into the potential molecular mechanism of cardiomyocyte apoptosis.

[Clinical results of ultrasound biometry in silicone oil-filled eye].

OBJECTIVE: To evaluate a method of ultrasound biometry in silicone oil-filled eye and its clinical results. METHODS: This was a series case study. According to the principle of measuring a distance with ultrasound, we compared the measured distance between a space filed with balanced salt solution and silicone oil at same height, to calculate a conversion factor (0.674) between them. A formula for corrective axial length in silicone oil-filled eye was established. The formula = ab + 0.674 x bc (a, b and c standing for the apex of the cornea, the posterior pole of the lens or the center of the capsular membrane and the anterior surface of the macular, respectively). The axial lengths of 150 silicone oil-filled eyes in 150 cases were then measured before and after silicone oil removal with Vivid 7 Dimension ultrasound. According to the axial length, they were divided into two groups, namely group 1 (the length < 25 mm) and group 2 (the length > or = 25 mm). In 76/150 eyes, before combined silicone oil removal and intraocular lens (IOL) implantation, the SRKT formula was used for intraocular lens calculation; the post-operative actual refraction was compared with the pre-operative predicted refraction and statistics analysis was made. RESULTS: The retinal condition of 150 silicone oil-filled eyes in 150 cases after 3 months' follow-up was stable after surgery. The results of the biometry were as follows. In the first group, the mean corrective axial lengths of 111 silicone oil-filled eyes before silicone oil removal was (22.77 +/- 1.00) mm (ranging from 21.10 to 24.90 mm); the mean axial lengths after silicone oil removal was (22.76 +/- 0.99) mm (ranging from 21.00 to 24.70 mm). The difference between them was not statistically significant (t = 0.518, P > 0.05). The vitreous cavity depth before and after silicone oil removal was (26.57 +/- 2.14) mm and (17.90 +/- 1.38) mm, respectively. The ratio of the latter to the former was 0.673 78. In the second group, the mean corrective axial lengths of 39 silicone oil-filled eyes before silicone oil removal was (26.52 +/- 1.31) mm (ranging from 25.00 to 30.58 mm); the mean axial lengths after silicone oil removal was (26.53 +/- 1.29) mm (ranging from 25.00 to 30.59 mm). The difference between them was not statistically significant (t = 0.109, P > 0.05). The vitreous cavity depth before and after silicone oil removal was (32.01 +/- 2.90) mm and (21.57 +/- 2.04) mm, respectively. The ratio of the latter to the former was 0.673 95. In 76 eyes with IOL, the post-operative actual refraction after at least 3 months follow-up was compared with the pre-operative predicted refraction (-1.50 DS) in both groups. The differences between them were not statistically significant (t(1) = 0.253, P(1) > 0.05; t(2) = 0.209, P(2) > 0.05) in each group. CONCLUSION: Ultrasound biometry in silicone oil-filled eye is accurate and simple, and has good results in clinical measurement.

Protein kinase C epsilon-dependent extracellular signal-regulated kinase 5 phosphorylation and nuclear translocation involved in cardiomyocyte hypertrophy with angiotensin II stimulation.

Angiotensin II (Ang II) plays a critical role in hypertrophy of cardiomyocytes; however, the molecular mechanism, especially the signaling cascades, in cardiomyocytes remains unclear. In the present study, we examined the mechanism of Ang II in hypertrophy of cardiomyocytes. Ang II rapidly stimulated phosphorylation of protein kinase C epsilon (PKCepsilon) in a time- and dose-dependent manner via Ang II receptor-1 (AT(1)). Furthermore, Ang II-induced extracellular signal-regulated kinase 5 (ERK5) phosphorylation and translocation was mediated through a signal pathway that involves AT(1) and PKCepsilon, which resulted in transcriptional activation of myocyte enhancer factor-2C (MEF2C) and hypertrophy. Consequently, inhibiting PKCepsilon or ERK5 by small interfering RNA (siRNA) significantly attenuated Ang II-induced MEF2C activation and hypertrophy of rat cardiomyocytes. These data provide evidence that PKCepsilon-dependent ERK5 phosphorylation and nucleocytoplasmic traffic mediates Ang II-induced MEF2C activation and cardiomyocyte hypertrophy. PKCepsilon and ERK5 may be potential targets in the treatment of pathological vascular hypertrophy associated with the enhanced renin-angiotensin system.

Atorvastatin reverses cardiac remodeling possibly through regulation of protein kinase D/myocyte enhancer factor 2D activation in spontaneously hypertensive rats.

The present study was designed to determine whether atorvastatin reduced hypertension-induced cardiac remodeling and whether these effects involved Protein Kinase D (PKD) and Myocyte Enhancer Factor 2D (MEF2D), factors known to be implicated in cardiac hypertrophy and fibrosis. 16-Week-old spontaneously hypertensive rats (SHRs) and age-matched Wistar-Kyoto (WKY) rats were included. Blood pressure and serum lipid concentration were measured. H-E staining, myocardial transverse diameter, and echocardiography were examined to evaluate cardiac hypertrophy. Hydroxyproline content assay and Masson's trichrome staining were used to estimate cardiac fibrosis. Atorvastatin (10, 25 and 50mg/kg/day) was administered for 8 weeks. Increased blood pressure and cardiac remodeling were prominent in SHRs compared with WKY rats. SHRs also had elevated PKD and MEF2D activation. The systolic blood pressure, myocardial transverse diameter and hydroxyproline content were positively correlated with the activation level of PKD and MEF2D in SHRs. Atorvastatin significantly attenuated the activation of PKD and MEF2D. It may be concluded that atorvastatin reverses hypertension-induced cardiac remodeling partially through down-regulation of PKD/MEF2D activation. Our results predict novel therapeutic targets for atorvastatin in treating hypertensive patients.

Hypertrophic response to angiotensin II is mediated by protein kinase D-extracellular signal-regulated kinase 5 pathway in human aortic smooth muscle cells.

Angiotensin II plays a critical role in hypertrophy of vascular smooth muscle cells, however, the molecular underpinnings remain unclear. The present study indicated that AT1/PKC/PKD pathway was able to regulate downstream ERK5, affecting pro-hypertrophic responses to Ang II. Ang II-stimulated phosphorylation of ERK5 in a time- and dose-dependent manner in human aortic smooth muscle cells (HASMCs). The pharmacological inhibitors for AT1 and PKCs significantly inhibited Ang II-induced ERK5 activation, suggesting the involvement of the AT1/PKC pathway. In particular, PKD was critical for Ang II-induced ERK5 activation since silencing PKD by siRNA markedly inhibited Ang II-induced ERK5 activation. Consequently, we found that Losartan, Gö 6983 and PKD siRNA significantly attenuated ERK5 activated translocation and hypertrophy of HASMCs by Ang II. Taken together, we demonstrated for the first time that Ang II activates ERK5 via the AT1/PKC/PKD pathway and revealed a critical role of ERK5 in Ang II-induced HASMCs hypertrophy.

Efficacy and safety of atorvastatin during early hospitalization in elderly patients with unstable angina.

1. Previous studies have demonstrated that early statin therapy after acute coronary syndrome decreases inflammation and mortality rates. The dose-response relationship for atorvastatin in elderly patients with unstable angina (UA) during early hospitalization in terms of lowering inflammatory factors, improving vascular endothelium function and safety is unclear. 2. In the present study, 166 consecutive patients with UA who were >/= 60 years of age were randomly assigned, in a double-blind manner, to receive 80 or 20 mg/day atorvastatin. High-sensitivity C-reactive protein, interleukin-6, tumour necrosis factor-alpha, fibrinogen and lipid levels were measured at admission and 1, 2 and 8 weeks later. Vascular endothelial function was measured and the safety of the drug was monitored. 3. Levels of inflammatory factors were significantly lower in patients on 80 mg atorvastatin than in those on 20 mg atorvastatin at 2 and 8 weeks. Atorvastatin 80 mg not only resulted in a significant improvement in vascular endothelial function during early hospitalization for UA over that seen in patients on 20 mg atorvastatin, but also reduced lipid levels to a greater extent. At 8 weeks, almost all patients showed good tolerance of 80 mg/day atorvastatin. 4. The results of the present study indicate that intensive statin therapy with high-dose (80 mg/day) atorvastatin is more efficacious than and as safe as 20 mg/day atorvastatin when administered to elderly patients during early hospitalization for UA.

Activation of ERK5 in angiotensin II-induced hypertrophy of human aortic smooth muscle cells.

Extracellular signal-regulated kinase 5 (ERK5), a recently discovered mitogen-activated protein kinase (MAPK), plays a key role in the development and pathogenesis of cardiovascular disease. In order to clarify the pathophysiological significance of ERK5 in vascular remodeling, we investigated ERK5 phosphorylation in hypertrophy of human aortic smooth muscle cells (HASMCs) induced by angiotensin II (Ang II). The AT1 receptor was involved in Ang II-induced ERK5 activity. Hypertrophy was detected by the measurement of protein synthesis with [(3)H]-Leu incorporation in cultured HASMCs. Ang II rapidly induced phosphorylation of ERK5 at Thr218/Tyr220 residues in a time- and dose-dependent manner. Activation of myocyte enhancer factor-2C (MEF2C) by ERK5 was inhibited by PD98059. Transfecting HASMCs with small interfering RNA (siRNA) to silence ERK5 inhibited Ang II-induced cell hypertrophy. Thus, ERK5 phosphorylation contributes to MEF2C activation and subsequent HASMC hypertrophy induced by Ang II, for a novel molecular mechanism in cardiovascular diseases induced by Ang II.

Upregulation of GRP78 and caspase-12 in diastolic failing heart.

BACKGROUND: The endoplasmic reticulum (ER) fulfills multiple cellular functions. Various stimuli can potentially cause ER stress (ERS). ERS is one of the intrinsic apoptosis pathways and apoptosis plays a critical role in hypertension. Glucose regulated protein 78 (GRP78) has been widely used as a marker for ERS and caspase-12 mediated apoptosis was a specific apoptotic pathway of ER. The expression of GRP78 and caspase-12 remains poorly understood in the diastolic heart failure resulting from hypertension. METHODS: We used spontaneously hypertensive rats (SHRs) to establish a model of diastolic heart failure, and performed immunohistochemistry, western blot, and real-time PCR to analyze GRP78 and caspase-12. RESULTS: We found that GRP78 and caspase-12 had enhanced expression at protein and mRNA levels. CONCLUSIONS: These results suggest that GRP78 and caspase-12 were upregulated in cardiomyocytes and ERS can contribute to cardiac myocyte apoptosis in the diastolic heart failure resulting from hypertension.

Biomarkers, age, and coronary artery remodeling in patients with acute coronary syndrome.

To investigate the relationship between age and coronary artery remodeling in patients with acute coronary syndrome (ACS), 56 patients with ACS were identified by intravascular ultrasound (IVUS). Remodeling index (RI) (37 cases of RI > or =1 vs 19 cases of RI <1) and dimidiate age groups (27 patients younger than 60 years vs 29 patients 60 years or older) were compared, and the relationships among biomarkers, age, and arterial remodeling were analyzed. There was a significant difference in age between positive and negative remodeling groups (55+/-13 vs 62+/-10 years; P=.038); RI and triglyceride level showed a statistical correlation (r=0.32; P=.02) and a significant inverse correlation between age and RI (r=-0.47; P<.001). The multivariable linear regression analysis demonstrated that age was an independent predictor of RI (Bate -0.37; 95% confidence interval, 0.93-1.08; P=.04). Age may be an important factor of arterial remodeling. Low-density lipoprotein or triglyceride level may be associated with attenuated coronary vascular remodeling with aging.

Relationship between tissue type plasminogen activator and coronary vulnerable plaque in patients with acute coronary syndrome: virtual histological study.

BACKGROUND: The association between vulnerability of plaque assessed with intravascular ultrasound (IVUS) and plasma levels of fibrinolytic biomarkers was determined in patients with acute coronary syndrome (ACS). However, few data are available on the relationship between the levels of tissue type plasminogen activator (t-PA) and virtual histological intravascular ultrasound (VH-IVUS) signs of plaque instability. METHODS: Eighty-nine patients with ACS were enrolled in the study. Blood was collected to measure t-PA levels by liquid phase bead flow cytometry. Eighty-nine nonbifurcate lesions (identified by coronary angiography and ECG) were investigated using IVUS before catheterization. IVUS radiofrequency data obtained with a 20 MHz catheter were analyzed with IVUS virtual histological software. The areas of plaque and media were calculated and lesions were classified into two groups: VH-IVUS derived thin cap fibroatheroma (VH-TCFA) and non-VH-TCFA plaque. RESULTS: Plasma t-PA level in the patients with TCFA was significantly lower than that with non-TCFA ((1489+/-715) pg/ml vs (2163+/-1004) pg/ml). Decreased plasma levels of t-PA were associated with plaque vulnerability. Plasma levels of t-PA correlated negatively with plaque plus media and necrotic core in plaque in patients with ACS. CONCLUSIONS: t-PA is an independent risk factor and a powerful predictor of vulnerable plaques. Decreased levels of t-PA may reflect instability of atherosclerotic plaques and might therefore serve as noninvasive determinants of those at high risk for consequent adverse events.

The involvement of transforming growth factor-beta1 secretion in urotensin II-induced collagen synthesis in neonatal cardiac fibroblasts.

As the most potent vasoconstrictor in mammals, urotensin II (U II) has recently been demonstrated to play an important role in adverse cardiac remodeling and fibrosis. However, the mechanisms of U II-induced myocardial fibrosis remain to be clarified. We postulated that U II alters transforming growth factor-beta1 (TGF-beta1) expression, and thereby modulates cardiac fibroblast collagen metabolism. Experiments were conducted using cardiac fibroblast from neonatal Wistar rats to determine the expression of TGF-beta1, and the role of U II receptor UT in this process. The functional role of TGF-beta1 and UT in modulating U II effects on type I, III collagen mRNA expression and 3H-proline incorporation was also analyzed. TGF-beta1 gene and protein expression were consistently identified in quiescent cardiac fibroblasts. U II increased the expression of TGF-beta1 mRNA and protein in a time-dependent manner. This effect was UT mediated, because UT antagonist urantide abolished U II-induced TGF-beta1 expression. U II-induced increase in type I, III collagen mRNA expression and 3H-proline incorporation were both inhibited by a specific TGF-beta1 neutralizing antibody and UT receptor antagonist urantide. Hence, our results indicate that TGF-beta1 is upregulated in cardiac fibroblasts by U II via UT and modulates profibrotic effects of U II. These findings provide novel insights into U II-induced cardiac remodeling.

[Relationship between serum vasoactive factors and plaque morphology in patients with acute coronary syndrome].

OBJECTIVE: To investigate the relationship between vasoactive factors and plaque morphology in patients with acute coronary syndrome (ACS). METHODS: Intravascular ultrasound (IVUS) were performed and 7 serum vasoactive factors (sPE, tPA, MCP-1, IL-8, IL-6, sVCAM-1 and sCD40L) were measured through cytometric bead array, serum hs-CRP, HCY, glucose and lipid level were also determined in consecutively enrolled 56 patients with ACS. The changes of bio-factors were compared between vulnerable plaque and non-vulnerable plaque groups, AMI and UA patients, and patients with or without plaque rupture. RESULTS: Biomarkers were similar between patients with unstable angina pectoris and AMI. hs-CRP [(18.9 +/- 4.9) mg/l vs. (5.8 +/- 3.6) mg/L)] and IL-6 [19.5 pg/ml (9.2 - 44.6 pg/ml) vs. 5.3 pg/ml (2.3 - 13.4 pg/ml)] were significantly higher in the group of vulnerable plaque (P < 0.05) compared to non-vulnerable plaques group. sCD40L [(474 +/- 126) pg/ml vs. (238 +/- 35) pg/ml], sPE [(107.2 +/- 39.9) microg/ml vs. (49.1 +/- 5.6) microg/ml] and MCP-1 [(132 +/- 18) pg/ml vs. (127 +/- 13) pg/ml] were significantly increased in the plaque rupture group than that in non-plaque rupture group (all P < 0.05). Increasing of sCD40L, MCP-1, sPE and TC were independent risk factors for plaque rupture. CONCLUSIONS: IL-6 and hs-CRP are biomarkers for vulnerable plaques and diagnosis of acute myocardial infarction. sCD40L, MCP-1 and sPE may serve as the potential markers predicting plaque rupture in patients with ACS.

Aging impairs insulin-stimulated glucose uptake in rat skeletal muscle via suppressing AMPKalpha

Insufficient intracellular fat oxidation is an important contributor to aging-related insulin resistance, while the precise mechanism underlying is unclear. AMP-activated protein kinase (AMPK) is an important regulator of intracellular fat oxidation and was evidenced to play a key role in high-glucose and high-fat induced glucose intolerance. In the present study, we investigated whether altered AMPK expression or activity was also involved in aging-related insulin resistance. Insulin sensitivity of rats' skeletal muscles was evaluated using in-vitro glucose uptake assay. Activity of alpha subunit of AMPK (AMPKalpha) was evaluated by measuring the phosphorylation of both AMPKalpha (P-AMPKalpha) and acetyl-CoA carboxylase (P-ACC), while expression of AMPKalpha was assessed by determining the mRNA levels of AMPKalpha1 and AMPKalpha2, and protein contents of AMPKalpha. Compared with 4-month old rats, 24-month old rats exhibited obviously impaired insulin sensitivity. At the same time, AMPKalpha activity significantly decreased, while AMPKalpha expression did not alter during aging. Glucose transporter 4 expression also decreased in old rats. Compared with 24-month old rats, administration of the specific activator of AMPK, 5-aminoimidazole-4-carboxamide riboside (AICAR), significantly elevated AMPKalpha activity and GluT4 expression. Also, aging-related insulin resistance was significantly ameliorated by AICAR treatment. In conclusion, aging-related insulin resistance is associated with impaired AMPKalpha activity and could be ameliorated by AICAR, thus indicating a possible role of AMPK in aging-induced insulin resistance.