Appropriate time for ejection fraction reassessment after revascularization in patients with left ventricular dysfunction for risk stratification of sudden cardiac death.

BACKGROUND: Appropriate time for ejection fraction (EF) reassessment after revascularization in patients with left ventricular dysfunction has not been investigated comprehensively, although 3 months after revascularization is recommended to stratify the risk of sudden cardiac death (SCD). HYPOTHESIS: EF reassessed within different timeframe after revascularization may have incosistent contribution for risk stratification of SCD. METHODS: Patients who had EF ≤ 40% before revascularization and had EF reassessment at least once during follow-up were included. The role of early (<3 months) versus late (3-12 months) EF measurements in prediction of all-cause mortality and SCD were compared. RESULTS: A total of 1589 patients were identified. EF reassessed <3 months was lower than EF reassessed within 3-12 months (42.1 ± 9.7% vs. 45.8 ± 10.8%; p < .01). Among 1069 patients who had EF reassessed <3 months, EF ≤ 35% was associated with a higher risk of all-cause mortality (hazard ratio [HR], 1.67; 95% confidence interval [CI], 1.22-2.29; p < .01), but had no association with the risk of SCD (HR, 1.44; 95% CI, 0.84-2.48; p = .18). By contrast, among 595 patients who had EF reassessed within 3-12 months, EF ≤ 35% was associated with higher risks of both all-cause death (HR, 1.81; 95% CI, 1.06-3.10; p = .03) and SCD (HR, 2.71; 95% CI, 1.31-5.61; p < .01). The relative contribution of SCD to all-cause death was higher in patients with EF ≤ 35% than patients with EF > 35% when EF was reassessed within 3-12 months (p = .04). However, when EF was reassessed <3 months, the mode of death was similar in patients with EF ≤ 35% versus >35% (p = .85). CONCLUSIONS: 3 to 12 months after revascularization may be appropriate for cardiac function reassessment and SCD risk stratification.

Determinants and clinical outcomes of stroke following revascularization among patients with reduced ejection fraction.

OBJECTIVE: Stoke after revascularization including both percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) is an uncommon but devastating complication. Patients with reduced ejection fraction (EF) had an increased risk of stroke after revascularization. However, little is known about the determinants and outcomes of stroke among patients with reduced EF following revascularization. MATERIALS AND METHODS: A cohort study of patients with preoperative reduced EF (≤40%) who received revascularization by either PCI or CABG between January 1, 2005 and December 31, 2014 was performed. Multivariate logistic regression was used to identify independent correlates of stroke. Logistic regression models were applied to evaluate the association of stroke with clinical outcomes. RESULTS: A total of 1937 patients were enrolled in this study. Of these, 111 (5.7%) patients suffered from stroke during the median 3.5-year follow-up. Older age (odds ratio [OR], 1.03; 95% CI, 1.01-1.05; p = .009), history of hypertension (OR, 1.79; 95% CI, 1.18-2.73; p = .007), and history of stroke (OR, 2.00; 95% CI, 1.19-3.36; p = .008) were found to be independent predictors for stroke. Patients with and without stroke had similar risk of all-cause death (OR, 0.91; 95% CI, 0.59-1.41; p = .670). However, stroke was associated with higher odds ratio of heart failure (HF) hospitalization (OR, 2.77; 95% CI, 1.74-4.40; p < .001) and composite end point (OR, 1.61; 95% CI, 1.07-2.42; p = .021). CONCLUSIONS: Further research appears warranted to minimize the complication of stroke and improve long-term outcomes among patients with reduced EF who underwent such high risk revascularization procedural.

Novel fabrication of bioengineered injectable chitosan hydrogel loaded with conductive nanoparticles to improve therapeutic potential of mesenchymal stem cells in functional recovery after ischemic myocardial infarction.

In recent decades, myocardial regeneration through stem cell transplantation and tissue engineering has been viewed as a promising technique for treating myocardial infarction. As a result, the researcher attempts to see whether co-culturing modified mesenchymal stem cells with Au@Ch-SF macro-hydrogel and H9C2 may help with tissue regeneration and cardiac function recovery. The gold nanoparticles (Au) incorporated into the chitosan-silk fibroin hydrogel (Au@Ch-SF) were validated using spectral and microscopic examinations. The most essential elements of hydrogel groups were investigated in detail, including weight loss, mechanical strength, and drug release rate. Initially, the cardioblast cells (H9C2 cells) was incubated with Au@Ch-SF macro-hydrogel, followed by mesenchymal stem cells (2 × 105) were transplanted into the Au@Ch-SF macro-hydrogel+H9C2 culture at the ratio of 2:1. Further, cardiac phenotype development, cytokines expression and tissue regenerative performance of modified mesenchymal stem cells treatment were studied through various in vitro and in vivo analyses. The Au@Ch-SF macro-hydrogel gelation time was much faster than that of Ch and Ch-SF hydrogels, showing that Ch and SF exhibited greater intermolecular interactions. The obtained Au@Ch-SF macro-hydrogel has no toxicity on mesenchymal stem cells (MS) or cardiac myoblast (H9C2) cells, according to the biocompatibility investigation. MS cells co-cultured with Au@Ch-SF macro-hydrogel and H9C2 cells also stimulated cardiomyocyte fiber restoration, which has been confirmed in myocardial infarction rats using -MHC and Cx43 myocardial indicators. We developed a novel method of co-cultured therapy using MS cells, Au@Ch-SF macro-hydrogel, and H9C2 cells which could promote the regenerative activities in myocardial ischemia cells. These study findings show that co-cultured MS therapy might be effective for the treatment of myocardial injury.

Smaller left ventricular end-systolic diameter and lower ejection fraction at baseline associated with greater ejection fraction improvement after revascularization among patients with left ventricular dysfunction.

Objectives: To investigate the predictive roles of pre-operative left ventricular (LV) size and ejection fraction (EF) in EF improvement and outcome following revascularization in patients with coronary artery disease (CAD) and LV dysfunction. Background: Revascularization may improve EF and long-term outcomes of patients with LV dysfunction. However, the determinants of EF improvement have not yet been investigated comprehensively. Materials and methods: Patients with EF measurements before and 3 months after revascularization were enrolled in a cohort study (No. ChiCTR2100044378). All patients had baseline EF ≤ 40%. EF improvement was defined as absolute increase in EF > 5%. According to LV end-systolic diameter (LVESD) (severely enlarged or not) and EF (≤35% or of 36-40%) at baseline, patients were categorized into four groups. Results: A total of 939 patients were identified. A total of 549 (58.5%) had EF improved. Both LVESD [odds ratio (OR) per 1 mm decrease, 1.05; 95% CI, 1.04-1.07; P < 0.001] and EF (OR per 1% decrease, 1.06; 95% CI, 1.03-1.10; P < 0.001) at baseline were predictive of EF improvement after revascularization. Patients with LVESD not severely enlarged and EF ≤ 35% had higher odds of being in the EF improved group in comparison with other three groups both in unadjusted and adjusted analysis (all P < 0.001). The median follow-up time was 3.5 years. Patients with LVESD not severely enlarged and EF ≤ 35% had significantly lower risk of all-cause death in comparison with patients with LVESD severely enlarged and EF ≤ 35% [hazard ratio (HR), 2.73; 95% CI, 1.28-5.82; P = 0.009], and tended to have lower risk in comparison with patients with LVESD severely enlarged and EF of 36-40% (HR, 2.00; 95% CI, 0.93-4.27; P = 0.074). Conclusion: Among CAD patients with reduced EF (≤ 40%) who underwent revascularization, smaller pre-operative LVESD and lower EF had greatest potential to have EF improvement and better outcome. Our findings imply the indication for revascularization in patients with LV dysfunction who presented with lower EF but smaller LV size.

Extent of Ejection Fraction Improvement After Revascularization Associated with Outcomes Among Patients with Ischemic Left Ventricular Dysfunction.

Purpose: Ejection fraction (EF) has been reported to be a major predictor of improved survival in patients with heart failure. However, it is largely unknown whether the extent of improvement in EF affects the subsequent risk of mortality. This study sought to investigate change in EF after revascularization and the implication of these changes on clinical outcomes among patients with ischemic left ventricular dysfunction. Patients and Methods: We conducted a cohort study (No. ChiCTR2100044378) of patients with reduced EF (≤40%) who received revascularization and had EF reassessment by echocardiography 3 months after revascularization. Patients were categorized according to the absolute change in EF: 1) EF worsened group (absolute decrease in EF >5%); 2) EF unchanged group (absolute change in EF -5% to 5%); 3) EF improved group (absolute increase in EF >5%). Results: Of 974 patients, 84 (8.6%) had EF worsened, 317 (32.5%) had EF unchanged and 573 (58.8%) had EF improved. The median follow-up time was 3.5 years, during which 143 patients died. For each 5-unit increments in EF, the risk of death decreased by 20% (hazard ratio, HR, per 5% increases, 0.80; 95% CI, 0.73-0.86; P<0.001). Compared with EF improvement group, patients with EF worsened (HR, 3.35; 95% CI, 2.07-5.42; P<0.001) and patients with EF unchanged (HR, 2.05; 95% CI, 1.40-3.01; P<0.001) had significantly higher risk of all-cause death. Conclusion: Changes in EF were inversely associated with the risk of mortality. The extent of EF improvement after revascularization might be a potential factor which defines clinical outcomes.

Predicting the Success Rate of Elective Percutaneous Coronary Intervention for Prior Failed Chronic Total Occlusion: a Novel Scoring System.

To investigate a scoring system for predicting the risk of successful percutaneous coronary intervention (PCI) after prior failed chronic total occlusion (CTO). Patients with previously attempted CTO-PCI were enrolled in our study retrospectively from January 2016 to December 2019. All clinical and procedural data were collected and analyzed. Univariate and multivariate logistic regression was performed to investigate the predictors of technical success. A total of 194 patients/CTO lesions were studied. The multivariate logistic regression showed that occlusion length < 20 mm (odds ratio (OR) = 2.94, score = 1), non-calcification (OR = 2.93, score = 1), adequate distal landing zone (OR = 4.46, score = 1), Rentrop grade ≥ 2 (OR = 5.98, score = 1), and retrograde approach as the initial strategy (OR = 10.28, score = 2) were predictors of the success of re-attempt PCI. The technical success rate for scores from 0 to ≥ 4 were 0%, 17.9%, 46.2%, 77.8%, and 93.3% respectively. Our scoring system can be used to predict the success rate of re-attempt CTO-PCI.

C-MYC ameliorates ventricular remodeling of myocardial infarction rats via binding to the promoter of microRNA-29a-3p to facilitate TET2 expression.

BACKGROUND: There is increasing evidence identifying the role of c-MYC in myocardial infarction (MI). Thus, our aim was to discuss the impact of c-MYC/microRNA (miR)-29a-3p/ten-eleven translocation-2 (TET2) axis on MI. METHODS: Sprague-Dawley rats received injections of recombinant adenoviruses at myocardial sites that interfered with c-MYC or miR-29a-3p expression. At 3 days after adenoviral injection, the rats were subjected to myocardial ischemia and reperfusion. Cardiac function, infarct size, cellular death, inflammatory response, oxidative stress, collagen deposition, c-MYC, TET2 and miR-29a-3p expression were analyzed. The interaction between c-MYC and miR-29a-3p as well as that between TET2 and miR-29a-3p was verified. RESULTS: miR-29a-3p expression was enhanced while c-MYC and TET2 expression was decreased in the myocardial tissue of MI rats. Up-regulating c-MYC or down-regulating miR-29a-3p in MI rat hearts improved cardiac function and reduced infarct size and myocardial apoptotic death, restrained oxidative stress, inflammatory response, attenuated collagen deposition. c-Myc bound to the promoter of miR-29a-3p and repressed miR-29a-3p expression. TET2 was a target of miR-29a-3p. CONCLUSION: Our study provides evidence that c-MYC binding to the promoter of miR-29a-3p to facilitate TET2 expression has therapeutic effect on ventricular remodeling of MI rats.

Diabetes Associated With Greater Ejection Fraction Improvement After Revascularization in Patients With Reduced Ejection Fraction.

Objectives: To investigate the association between diabetes mellitus (DM) and ejection fraction (EF) improvement following revascularization in patients with coronary artery disease (CAD) and left ventricular (LV) dysfunction. Background: Revascularization may improve outcomes of patients with LV dysfunction by improvement of EF. However, the determinants of EF improvement have not yet been investigated comprehensively. Method: A cohort study (No. ChiCTR2100044378) of patient with repeated EF measurements after revascularization was performed. All patients had baseline EF ≤40%. Patients who had EF reassessment 3 months after revascularization were enrolled. Patients were categorized into EF unimproved (absolute increase in EF ≤5%) and improved group (absolute increase in EF >5%). Results: A total of 974 patients were identified. 573 (58.8%) had EF improved. Patients with DM had greater odds of being in the improved group (odds ratio [OR], 1.42; 95% CI, 1.07-1.89; P = 0.014). 333 (34.2%) patients with DM had a greater extent of EF improvement after revascularization (10.5 ± 10.4 vs. 8.1 ± 11.2%; P = 0.002) compared with non-diabetic patients. The median follow-up time was 3.5 years. DM was associated with higher risk of overall mortality (hazard ratio [HR], 1.46; 95% CI, 1.02-2.08; P = 0.037). However, in EF improved group, the risk was similar between diabetic and non-diabetic patients (HR, 1.36; 95% CI, 0.80-2.32; P = 0.257). Conclusions: Among patients with reduced EF, DM was associated with greater EF improvement after revascularization. Revascularization in diabetic patients might partially attenuate the impact of DM on adverse outcomes. Our findings imply the indication for revascularization in patients with LV dysfunction who present with DM.

Clinical Outcomes of Patients with Coronary Artery Diseases and Moderate Left Ventricular Dysfunction: Percutaneous Coronary Intervention versus Coronary Artery Bypass Graft Surgery.

PURPOSE: Percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) are two revascularization strategies for patients with coronary artery disease (CAD) and left ventricular dysfunction. However, the comparisons of effectiveness between the two strategies are insufficient. This study is aimed to compare the effectiveness between PCI and CABG among patients with moderate left ventricular dysfunction. PATIENTS AND METHODS: A total of 1487 CAD patients with moderate reduced ejection fraction (36%≤EF≤40%), who underwent either PCI or CABG, were enrolled in a real-world cohort study (No. ChiCTR2100044378). Clinical outcomes included short- and long-term all-cause mortality, rates of heart failure (HF) hospitalization and repeat revascularization. Propensity score matching was used to balance the two cohorts. RESULTS: PCI was associated with lower 30-day mortality rate (hazard ratio [HR] [95% CI], 0.35 [0.15-0.83]; P=0.02). At a mean follow-up of 4.5 years, PCI and CABG had similar all-cause death (HR [95% CI], 0.82 [0.56-1.20]; P=0.30) and heart failure (HF) hospitalization (HR [95% CI], 0.93 [0.54-1.60]; P=0.79), but PCI had higher risk of repeat revascularization (HR [95% CI], 8.62 [3.67-20.23]; P<0.001). Improvement in EF measured at 3 months later after revascularization was also similar between PCI and CABG (P for interaction=0.87). CONCLUSION: CAD patients with moderate reduced EF who had PCI had lower short-term mortality rate but higher risk of repeat revascularization during follow-up than patients who had CABG. PCI showed comparable long-term survival, HF hospitalization risk, and EF improvement.

BMSCs-derived exosomal microRNA-150-5p attenuates myocardial infarction in mice.

OBJECTIVE: MicroRNAs (miRNAs) have engaged in the progression of myocardial infarction (MI). Nevertheless, the mechanism of miR-150-5p in MI is still in its infancy. Therefore, the present study was set out to investigate the effect of bone marrow mesenchymal stem cells derived exosomes (BMSCs-Exo) and miR-150-5p in MI via regulating B-cell lymphoma-associated X (Bax). METHODS: BMSCs-Exo were isolated and extracted, and exosomes with miR-150-5p agomir or antagomir was constructed. Then, a mouse MI model was induced by ligation of left anterior descending coronary artery. Mice were injected with exosomes and miR-150-5p agomir/antagomir to detect cardiac function, pathological changes, and apoptosis rate of cardiomyocytes. miR-150-5p and Bax expression in myocardial tissues were tested. The targeting relationship between miR-150-5p and Bax was verified. RESULTS: BMSCs and exosomes were successfully extracted. BMSCs-derived exosomal miR-150-5p improved cardiac function, alleviated pathological changes of myocardium, decreased apoptosis rate of cardiomyocytes in MI mice. miR-150-5p expression was reduced and Bax expression was elevated in myocardial tissues of MI mice, while exosomes raised miR-150-5p expression and reduced Bax expression in MI mice. miR-150-5p was found to target Bax. CONCLUSION: On all accounts, the present study provides evidence that BMSCs-derived exosomal miR-150-5p attenuates apoptosis of cardiomyocytes and improves cardiac function of MI mice via targeting Bax.

Pleiotropic Effects of Simvastatin on the Regulation of Potassium Channels in Monocytes.

PURPOSE: The underlying mechanism of pleiotropic effects of statins on atherosclerosis is still unclear. Kv1.3 and KCa3.1 are two potassium channels that might be involved in monocyte migration and atherosclerosis formation. The aim of this study was to investigate the effect of simvastatin on the Kv1.3 and KCa3.1 in monocyte. METHODS AND RESULTS: In human monocytic THP-1 cells, simvastatin significantly inhibited Kv1.3 mRNA and protein expression by real-time quantitative PCR analysis and western blotting. However, simvastatin had no effects on KCa3.1 mRNA and protein expression. By whole-cell patch clamp, simvastatin (10 µM) remarkably inhibited the current intensity of Kv1.3, but had no effect on KCa3.1. Simvastatin (10 µM) treatment significantly reduced the monocyte chemoattractant protein 1 (MCP-1)-induced monocyte migration. This inhibition was only partially reversed by mevalonate (1mM). In human peripheral blood mononuclear cells (PBMCs), both Kv1.3 and KCa3.1 mRNA expression were increased in patients with coronary artery diseases (CAD) (n = 20) compared to healthy controls (n = 22). However, simvastatin (40 mg per day) significantly inhibited the Kv1.3 but not KCa3.1 mRNA expression after 1 month and 3 months therapy in CAD patients. CONCLUSION: Our data suggested Kv1.3 in monocytes was a potential molecular target of the pleiotropic effects of statins. KCa3.1 might be another marker of CAD, but not associated with statins treatment.

Computed tomography coronary angiography vs. standard diagnostic procedure for the diagnosis of angina due to coronary heart disease: A cross-sectional study.

Patients with episodes of angina are likely to experience future cardiac events and benefit from a revascularization procedure. Conventional invasive coronary angiography is a well-established and reliable method for the detection of angina, but it has a risk of complications and false-negative diagnosis. The objective of the present study was to assess the utility of computed tomography coronary angiography (CTCA) in the diagnosis of angina due to coronary heart disease. A total of 2,426 patients with chest pain referred to the rapid access chest pain clinic of Beijing Anzhen Hospital, Capital Medical University (Beijing, P.R. China) between 18 January 2016 and 1 December 2017 were included in the present cross-sectional study. All patients were subjected to evaluation of symptoms, blood tests, 12-lead electrocardiogram (ECG), exercise ECG, coronary artery calcium scoring and CTCA. The cost of the diagnosis of angina was determined for each individual method. In total, 776 (32%) and 1,420 (58%) of patients were identified to be abnormal on clinical assessment and CTCA, respectively. Exercise ECG results were not correlated with the interpretation of CTCA (r=0.8511). The working area of the angina due to coronary heart disease detected at one time by the different diagnostic procedures was in the order of ECG

Fibroblast Growth Factor 21 Attenuates Vascular Calcification by Alleviating Endoplasmic Reticulum Stress Mediated Apoptosis in Rats.

Fibroblast growth factor 21 (FGF21), a hormone with multiple metabolic properties, has proven to be pleiotropic biological effects and may play pivotal role in numerous cardiovascular and metabolic diseases in the future. Vascular calcification (VC) is a concomitant pathological process of various cardiovascular and metabolic diseases. However, the effects of FGF21 on VC remain unclear. Therefore, in this research, we aimed to explore the roles and mechanisms of FGF21 in VC induced by vitamin D3 plus nicotine (VDN) treatment rats. After 28 days VDN treatment, the calcium overload was confirmed by blood pressure, ultrasound imaging, calcium content, ALP activity and aortic pathological characteristics. In terms of FGF21, exogenous FGF21 can ameliorate the elevation of blood pressure, aortic calcification and related injury in VC rats. To investigate the mechanisms of FGF21 on VC, the endoplasmic reticulum stress (ERS) mediated apoptosis pathways were tested. As a method to detect apoptosis, the increased positive TUNEL staining cells were alleviated by FGF21 treatment. Furthermore, exogenous FGF21 can suppress the increased ERS chaperone, GRP78, in the calcified aortas. In the three pathways of ERS mediated apoptosis, we found CHOP pathway and caspase-12 pathway were involved in the treatment of FGF21, but not p-JNK/JNK pathway. Our study proved for the first time that FGF21 can inhibit the progress of VC by alleviating ERS mediated apoptosis in rats. FGF21 might be a new target for preventing and treating VC.

Protection Effect of Exogenous Fibroblast Growth Factor 21 on the Kidney Injury in Vascular Calcification Rats.

BACKGROUND: Chronic kidney disease (CKD) is closely related to the cardiovascular events in vascular calcification (VC). However, little has known about the characteristics of kidney injury caused by VC. Fibroblast growth factor 21 (FGF21) is an endocrine factor, which takes part in various metabolic actions with the potential to alleviate metabolic disorder diseases. Even FGF21 has been regarded as a biomarker in CKD, the role of FGF21 in CKD remains unclear. Therefore, in this study, we evaluate the FGF21 on the kidney injury in VC rats. METHODS: The male Sprague-Dawley rats were divided into three groups: (1) control group, (2) Vitamin D3 plus nicotine (VDN)-induced VC group, (3) FGF21-treated VDN group. After 4 weeks, the rats were killed and the blood was collected for serum creatinine, urea nitrogen, calcium, and phosphate measurement. Moreover, the renal tissues were homogenized for alkaline phosphatases (ALPs) activity and calcium content. The levels of FGF21 protein were measured by radioimmunoassay. The levels of ß-Klotho and FGF receptor 1 (FGFR1) protein were measured by enzyme-linked immunosorbent assay (ELISA). The structural damage and calcifications in aortas were stained by Alizarin-red S. Moreover, the structure of kidney was observed by hematoxylin and eosin staining. RESULTS: The renal function impairment caused by VDN modeling was ameliorated by FGF21 treatment, inhibited the elevated serum creatinine and urea level by 20.5% (34.750 ± 4.334 µmol/L vs. 27.630 ± 2.387 µmol/L) and 4.0% (7.038 ± 0.590 mmol/L vs. 6.763 ± 0.374 mmol/L; P < 0.01), respectively, together with the structural damages of glomerular atrophy and renal interstitial fibrosis. FGF21 treatment downregulated the ALP activity, calcium content in the kidney of VC rats by 42.1% (P < 0.01) and 11.7% (P < 0.05) as well as ameliorated the aortic injury and calcification as compared with VDN treatment alone group, indicating an ameliorative effect on VC. ELISA assays showed that the expression of ß-Klotho, a component of FGF21 receptor system, was increased in VDN-treated VC rats by 37.4% (6.588 ± 0.957 pg/mg vs. 9.054 ± 0.963 pg/mg; P < 0.01), indicating an FGF21-resistant state. Moreover, FGF21 treatment downregulated the level of ß-Klotho in renal tissue by 16.7% (9.054 ± 0.963 pg/mg vs. 7.544 ± 1.362 pg/mg; P < 0.05). However, the level of FGFR1, the receptor of FGF21, kept unchanged under VDN and VDN plus FGF21 administration (0.191 ± 0.0376 ng/mg vs. 0.189 ± 0.032 ng/mg vs. 0.181 ± 0.034 ng/mg; P > 0.05). CONCLUSIONS: In the present study, FGF21 was observed to ameliorate the kidney injury in VDN-induced VC rats. FGF21 might be a potential therapeutic factor in CKD by cutting off the vicious circle between VC and kidney injury.

A simple score for predicting renal artery stenosis in patients with ischemic heart disease.

BACKGROUND: Previous risk score is not simple for predicting existence of atherosclerotic renal artery stenosis (ARAS). Our study aims to develop a simple score to predict ARAS in eastern people with ischemic heart disease. METHODS: There were two data sources involved in this study. From the data source of patients with acute myocardial infarction, we developed a clinical score for predicting existence of ARAS. After this, we validated this clinical score in data source of patients with ischemic heart failure. RESULTS: By multivariable logistic regression analysis, only age, hypertension, stroke or intermittent claudication, serum creatinine were involved in this model. Receiver operating characteristic curve was plotted. In the first data source, area under curve is 0.808 to predict ARAS, and 0.762 for bilateral ARAS. In the second data source, area under curve is 0.721 to predict ARAS, and 0.827 for ARAS. Cutoff value of 35.0 yields a sensitivity of 82.4% and a specificity of 51.0% for ARAS, a sensitivity of 78.9% and a specificity of 47.1% for bilateral ARAS. In the second data source, this cutoff value yields a sensitivity of 85.0% and a specificity of 30.5% for ARAS, a sensitivity of 85.7% and a specificity of 17.5% for bilateral ARAS. CONCLUSIONS: We have developed a simple score for eastern people to predicting existence of ARAS with acceptable sensitivity and specificity in patients with ischemic heart disease. This score is still needed to be validated in general population or patients with no coronary heart disease.

Possible role of fibroblast growth factor 21 on atherosclerosis via amelioration of endoplasmic reticulum stress-mediated apoptosis in apoE(-/-) mice.

Fibroblast growth factor 21 (FGF-21) is an endocrine factor that can be secreted into circulation by the liver. FGF-21 takes part in metabolic actions and is thought to be a promising candidate for the treatment of diabetes. However, the role of FGF-21 in atherosclerosis is unknown. In this study, apoE(-/-) mice were fed an atherogenic diet for 4 weeks with and without subcutaneous injections of FGF-21. ApoE(-/-) mice fed an atherogenic diet showed hyperlipidemia, a large plaque area in aortas and increased vessel wall thickness. Plasma FGF-21 content and protein level of FGF receptor 1 (FGFR1) in aortas was greater in apoE(-/-) than C57BL/6J mice. Exogenous FGF-21 treatment significantly ameliorated dyslipidemia in apoE(-/-) mice. FGF-21-treated apoE(-/-) mice showed reduced number of aortic plaques and plaque area as well as reduced number of TUNEL-positive cells. Protein levels of the endoplasmic reticulum stress markers glucose-regulated protein 94, caspase-12 and C/EBP homologous protein were reduced by 34.5, 31.4 and 26.5 %, respectively, in apoE(-/-) mice. Endogenous expression of FGF-21 and its receptor FGFR1 were upregulated in apoE(-/-) mice, and exogenous administration of FGF-21 ameliorated the atherogenic-induced dyslipidemia and vascular atherosclerotic lesions. FGF-21 protecting against atherosclerosis might be in part by its inhibitory effects on endoplasmic reticulum stress-mediated apoptosis.

BMP-2 overexpression augments vascular smooth muscle cell motility by upregulating myosin Va via Erk signaling.

BACKGROUND: The disruption of physiologic vascular smooth muscle cell (VSMC) migration initiates atherosclerosis development. The biochemical mechanisms leading to dysfunctional VSMC motility remain unknown. Recently, cytokine BMP-2 has been implicated in various vascular physiologic and pathologic processes. However, whether BMP-2 has any effect upon VSMC motility, or by what manner, has never been investigated. METHODS: VSMCs were adenovirally transfected to genetically overexpress BMP-2. VSMC motility was detected by modified Boyden chamber assay, confocal time-lapse video assay, and a colony wounding assay. Gene chip array and RT-PCR were employed to identify genes potentially regulated by BMP-2. Western blot and real-time PCR detected the expression of myosin Va and the phosphorylation of extracellular signal-regulated kinases 1/2 (Erk1/2). Immunofluorescence analysis revealed myosin Va expression locale. Intracellular Ca(2+) oscillations were recorded. RESULTS: VSMC migration was augmented in VSMCs overexpressing BMP-2 in a dose-dependent manner. siRNA-mediated knockdown of myosin Va inhibited VSMC motility. Both myosin Va mRNA and protein expression significantly increased after BMP-2 administration and were inhibited by Erk1/2 inhibitor U0126. BMP-2 induced Ca(2+) oscillations, generated largely by a "cytosolic oscillator". CONCLUSION: BMP-2 significantly increased VSMCs migration and myosin Va expression, via the Erk signaling pathway and intracellular Ca(2+) oscillations. We provide additional insight into the pathophysiology of atherosclerosis, and inhibition of BMP-2-induced myosin Va expression may represent a potential therapeutic strategy.

Aging aggravates nitrate-mediated ROS/RNS changes.

Nitrates are the most frequently prescribed and utilized drugs worldwide. The elderly are a major population receiving nitrate therapy. Both nitrates and aging can increase in vivo reactive oxygen species (ROS) and reactive nitrogen species (RNS). To date, the effects of aging upon nitrate-induced ROS/RNS alteration are unknown. The present study tested the effects of aging upon nitrate-induced ROS/RNS alteration in vivo. 32 adults and 43 elderly unstable angina (UA) patients were subjected to 48 hours of isosorbide dinitrate intravenous injection (50 µg/minutes) in this clinical study. Blood samples were obtained at baseline and conclusion. Outcome measures of oxidative stress included plasma malondialdehyde (MDA), myeloperoxidase (MPO), and reduced glutathione (GSH). Plasma concentrations of NOx and nitrotyrosine served as markers of RNS. Because of the significant differences in basic clinical characters between adults and the elderly, we designed an additional experiment determining ROS/RNS stress in rat cardiac tissue. Additionally, rat thoracic aortic NOS activity served as a marker indicating endothelial function. Our study demonstrated that nitrate therapy significantly increased in vivo ROS/RNS stress in the elderly compared to adult patients, confirmed by animal data. Decreased NOS activity was observed in old rats. Taken together, the present study's data suggests a synergism between nitrate treatment and the aging process.

Is it necessary to stent renal artery stenosis patients before cardiopulmonary bypass procedures?

BACKGROUND: Acute kidney injury (AKI) is associated with poor prognosis after cardiopulmonary bypass. The aim of this retrospective study was to investigate whether stent implantation before cardiopulmonary bypass has beneficial effect on development of AKI in renal artery stenosis (RAS) patients. METHODS: In this retrospective study, patients with abnormal baseline serum creatinine (SCr, > 106 µmol/L) were not included. Included patients (n = 69) were divided into two groups. Group 1 included 31 RAS patients receiving no stent implantation before cardiopulmonary bypass. Group 2 included 38 RAS patients having received stent implantation just before cardiopulmonary bypass. To assess AKI after cardiopulmonary bypass, serum urea nitrogen, SCr and creatinine clearance were recorded at baseline, at the end of operation, during the first and second postoperative 24 hours. RESULTS: Baseline characteristics were similar between groups. Serum urea nitrogen, SCr, creatinine clearance before and after cardiopulmonary bypass were also similar class groups. Incidence of AKI in group 1 was not significantly different from group 2. In group 1, AKI defined by RIFLE between occurred in 7 (22.6%) patients: 5 (16.1%) with RIFLE-R, 2 (6.5%) with RIFLE-I, and no patients with RIFLE-F. In group 2, 10 patients (26.3%) had an episode of AKI during hospitalization: 6 (15.8%) had RIFLE-R, 4 (10.5%) had RIFLE-I, and no patients had RIFLE-F. CONCLUSIONS: There are no data suggesting that it is necessary to stent RAS patients with normal SCr before cardio-pulmonary bypass. However, it cannot be concluded that RAS is not associated with AKI after cardiopulmonary bypass.