The 10-Year Prognosis and Prevalence of Brugada-Type Electrocardiograms in Elderly Women: A Longitudinal Nationwide Community-Based Prospective Study.

BACKGROUND: Brugada syndrome is a disorder associated with sudden cardiac death and characterized by an abnormal electrocardiogram (ECG). Previous studies were predominantly conducted in men, and the data on long-term prognosis are limited. Information about women, especially elderly women, is lacking. OBJECTIVE: The aim of this study was to investigate the long-term prognosis of the Brugada ECG pattern in elderly women. METHOD: We investigated the 10-year prognosis of the Brugada ECG pattern in elderly women in a nationwide community-based population in Taiwan. Community-dwelling women older than 55 years were prospectively recruited from December 2008 to March 2013 by a stratified random sampling method. All enrolled individuals were followed up annually until April 2019, and the cause of death was documented by citizen death records. RESULTS: Among 2597 women, 60 (2.31%) had a Brugada-type ECG, and this prevalence was higher than the mean global prevalence of 0.23%. One woman had a type 1 ECG (0.04%), whereas 15 (0.58%) and 44 (1.70%) women had type 2 and type 3 ECG patterns, respectively. Cox survival analysis revealed that all-cause mortality and cardiac mortality were similar in the individuals with and without a Brugada-type ECG during a mean follow-up of 96.1 ± 20.5 months. CONCLUSIONS: Our findings suggest that Brugada ECG patterns are not infrequent in elderly women but are not associated with increased risk of mortality in long-term follow-up; these findings may help reduce unnecessary anxiety for physicians, nurses, allied health caregivers, and patients.

Chrysin Inhibits High Glucose-Induced Migration on Chorioretinal Endothelial Cells via VEGF and VEGFR Down-Regulation.

BACKGROUND: Diabetes mellitus (DM) is a chronic inflammatory disease, which causes multiple complications. Diabetic retinopathy (DR) is among these complications and is a dominant cause of vision loss for diabetic patients. Numerous studies have shown that chrysin, a flavonoid, has many biological activities such as anti-oxidation and anti-inflammation. However, it is rarely used in ocular diseases. In this study, we examined the inhibitory effects of flavonoid on high glucose induced migration of chorioretinal endothelial cells (RF/6A cells) and its mechanism. MATERIALS AND METHODS: The viability of RF/6A cells treated with chrysin was examined with a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The migration of RF/6A cells was assessed by the transwell migration and scratch wound assays. The expression of AKT, ERK, vascular endothelial growth factor (VEGF), HIF-1α and MMP-2 were determined by western blotting. To observe the mRNA expression of VEGF receptor (VEGFR), qRT-PCR, was utilized. RESULTS: The results showed that chrysin can dose-dependently inhibit the RF/6A cell migration in vitro transwell and the scratch wound assays which are induced by high glucose. After pretreatment of RF/6A cells with different concentrations of chrysin, they did not produce any cytotoxicity in MTT assay. Moreover, chrysin down-regulated both phosphorylated AKT and ERK, as well as attenuated the expression levels of MMP-2. It also decreased the expression of the VEGF transcription factor and VEGF. Furthermore, it was shown that chrysin could suppress the protein and mRNA expression levels of VEGFR. CONCLUSION: The results indicate that chrysin could down-regulate the phosphorylation of AKT, ERK and MMP-2 and reduce the effects of VEGF and VEGFR in a high glucose environment. It further inhibits the high glucose-induced migration of RE/6A cells. Therefore, chrysin may have the potential for visual protection.

Comparison of Arrhythmia Detection by 24-Hour Holter and 14-Day Continuous Electrocardiography Patch Monitoring.

BACKGROUND: Although 24-hour Holter monitoring is routinely used for patients with suspected paroxysmal arrhythmia, its sensitivity in detecting such arrhythmias is insufficient. METHODS: We compared a 14-day electrocardiography (ECG) monitor patch - a single-use, noninvasive, waterproof, continuous monitoring patch - with a 24-hour Holter monitor in 32 consecutive patients with suspected arrhythmia. RESULTS: The 14-day ECG patch was well tolerated, and its rates of detection of relevant arrhythmias on days 1, 3, 7, and 14 were 13%, 28%, 47%, and 66%, respectively. The detection rate of paroxysmal arrhythmias was significantly higher for the 14-day ECG patch than for the 24-hour Holter monitor (66% vs. 9%, p < 0.001). Among the 32 patients, 202 atrial fibrillation or atrial flutter episodes were detected in 6 patients (22%) with the 14-day ECG patch; however, only 1 atrial fibrillation episode was detected in a patient (3%, p < 0.05) with the 24-hour Holter monitor. Other clinically relevant arrhythmias recorded on the 14-day ECG patch included 21 (65.5%) episodes of supraventricular tachycardia, 2 (6.3%) long pause, and 2 (6.3%) ventricular arrhythmias. The mean dermal response score immediately after removal of the 14-day ECG patch from the patients was 0.64, which indicated minimal erythema. CONCLUSIONS: The 14-day ECG patch was well tolerated and allowed for longer continuous monitoring than the 24-hour Holter monitor, thus resulting in improved clinical accuracy in the detection of paroxysmal arrhythmias. Future studies should examine the long-term effectiveness of 14-day ECG patches for managing selected patients.

Effect of atorvastatin on cardiomyocyte hypertrophy through suppressing MURC induced by volume overload and cyclic stretch.

MURC (muscle-restricted coiled-coil protein) is a hypertrophy-related gene. Hypertrophy can be induced by mechanical stress. The purpose of this research was to investigate the hypothesis that MURC mediates hypertrophy in cardiomyocytes under mechanical stress. We used the in vivo model of an aortocaval shunt (AV shunt) in adult Wistar rats to induce myocardial hypertrophy. We also used the in vitro model of cyclic stretch in rat neonatal cardiomyocytes to clarify MURC expression and the molecular regulation mechanism. The flexible membrane culture plate seeding with cardiomyocytes Cardiomyocytes seeded on a flexible membrane culture plate were stretched by vacuum pressure to 20% of maximum elongation at 60 cycles/min. AV shunt induction enhanced MURC protein expression in the left ventricular myocardium. Treatment with atorvastatin inhibited the hypertrophy induced by the AV shunt. Cyclic stretch markedly enhanced MURC protein and mRNA expression in cardiomyocytes. Addition of extracellular-signal-regulated kinase (ERK) inhibitor PD98059, ERK small interfering RNA (siRNA), angiotensin II (Ang II) antibody and atorvastatin before stretch, abolished the induction of MURC protein. An electrophoretic mobility shift assay showed that stretch enhanced the DNA binding activity of serum response factor. Stretch increased but MURC mutant plasmid, ERK siRNA, Ang II antibody and atorvastatin reversed the transcriptional activity of MURC induced by stretch. Adding Ang II to the cardiomyocytes also induced MURC protein expression. MURC siRNA and atorvastatin inhibited the hypertrophic marker and protein synthesis induced by stretch. Treatment with atorvastatin reversed MURC expression and hypertrophy under volume overload and cyclic stretch.

A Phenanthrene Derivative, 5,7-Dimethoxy-1,4-Phenanthrenequinone, Inhibits Cell Adhesion Molecule Expression and Migration in Vascular Endothelial and Smooth Muscle Cells.

The activation of endothelial cells (ECs) and migration of vascular smooth muscle cells (VSMCs) have played a crucial role in monocyte chemotaxis/adhesion and intima thickening during vascular injury and atherosclerosis, respectively. Several phenanthrenes isolated from plants and natural products have been shown to possess different bioactivities such as anti-platelet aggregation and anti-inflammation. The current study was designated to investigate the effects of a phenanthrene derivative, 5,7-dimethoxy-1,4-phenanthrenequinone (DMPQ), on cell adhesion molecule (CAM) expression in vascular ECs and migration in VSMCs. The DMPQ attenuated monocyte-EC interaction but it did not affect monocyte adhesion to matrix. In parallel, DMPQ reduced tumor necrosis factor-α (TNF-α)-induced intercellular adhesion molecule and vascular CAM expression in ECs. DMPQ compromised TNF-α-induced IκB activation, nuclear factor-kappa B (NF-κB) translocation, and NF-κB-DNA complex formation. Moreover, it affected TNF-α- and hydrogen peroxide (H2O2)-induced reactive oxygen species production and IκB activation. These suggest that DMPQ affects CAM expression by affecting NF-κB signaling. Meanwhile, DMPQ could also inhibit platelet-derived growth factor (PDGF)-induced VSMC migration toward collagen by affecting cellular PDGF signaling, including PDGFRß, PLCγ, ERK1/2, and Akt phosphorylation. The VSMC adhesion to collagen and collagen-induced focal adhesion kinase activation during cell adhesion were impaired by DMPQ treatment. This study reveals a phenanthrene derivative-DMPQ-with anti-inflammatory and anti-migratory bioactivity toward vascular ECs and SMCs, suggesting its protective effect on vascular injuries.

Atorvastatin alleviates cardiomyocyte apoptosis by suppressing TRB3 induced by acute myocardial infarction and hypoxia.

BACKGROUND/PURPOSE: TRB3 (tribbles 3), an apoptosis-regulated gene, increases during endoplasmic reticulum stress. Hypoxia can induce inflammatory mediators and apoptosis in cardiomyocytes. However, the expression of TRB3 in cardiomyocyte apoptosis under hypoxia is not thoroughly known. We investigated the regulation mechanism of TRB3 expression and apoptosis induced by hypoxia in cardiomyocytes. METHODS: An in vivo model of acute myocardial infarction (AMI) was applied in adult Wistar rats to induce myocardial hypoxia. Rat neonatal cardiomyocytes were subjected to 2.5% O2 to induce hypoxia. RESULTS: The expression of TRB3 was evaluated in cultured rat neonatal cardiomyocytes subjected to hypoxia. Hypoxia significantly enhanced TRB3 protein and mRNA expression. Adding c-jun N-terminal kinase (JNK) inhibitor SP600125, JNK small interfering RNA (siRNA), tumor necrosis factor-α (TNF-α) antibody, and atorvastatin 30 minutes before hypoxia reversed the induction of TRB3 protein. A gel-shift assay showed the DNA-binding activity of growth arrest and DNA damage-inducible gene 153 (GADD153), which increased after hypoxia. Hypoxia increased, whereas the TRB3-mut plasmid, SP600125, and TNF-α antibody abolished the hypoxia-induced TRB3 promoter activity. Hypoxia increased the secretion of TNF-α from cardiomyocytes. Exogenous administration of TNF-α recombinant protein to the cardiomyocytes without hypoxia increased TRB3 protein expression, similar to that observed after hypoxia. Hypoxia-induced cardiomyocyte apoptosis is inhibited by TRB3 siRNA, the TNF-α antibody, and atorvastatin. Atorvastatin reduced the TRB3 expression and cardiomyocyte apoptosis induced by AMI. Hypoxia induces TRB3 through TNF-α, JNK, and the GADD153 pathway. CONCLUSION: Treatment of atorvastatin inhibits the expression of TRB3 and cardiomyocyte apoptosis induced by AMI and hypoxia.

Prognostic impact of renal dysfunction in patients with acute coronary syndrome-role beyond the CHA2 DS2 -VASc score: Data from Taiwan acute coronary syndrome full spectrum registry.

AIM: CHA2 DS2 -VASc score has been proven to have great prognostic value in patients with acute coronary syndrome (ACS). We aimed to determine whether the addition of renal dysfunction in the CHA2 DS2 -VASc score would improve the prognostic impact of the scoring system to predict prognosis among ACS patients. METHODS: A total of 3031 ACS patients were prospectively enrolled at 39 hospitals and followed for 1 year. The patients were divided into three groups based on estimated glomerular filtration rate (eGFR) (group 1, eGFR>90; group 2, eGFR between 60 and 90; and group 3, eGFR<60 mL/min per 1.73 m(2) ). The occurrence of subsequent myocardial infarction (MI), stroke, or death was recorded. RESULTS: As renal function progressively decreased from group 1 to 3, the patients were, respectively older and had higher incidence of comorbidity, worse Killip classification, and less evidence-based medical therapies. The rate of subsequent MI, stroke or death increased from 3.4% in group 1 to 7.4% in group 2 and 17.2% in group 3 (P < 0.001). Renal dysfunction (eGFR<60 mL/min per 1.73 m(2) ) and CHA2 DS2 -VASc scores were both significant predictors of adverse events in multivariable regression analyses. Renal dysfunction can further stratify patients with CHA2 DS2 -VASc score of 0 or 1 into 3 groups with different adverse event rates (group 1, 3.0%; group 2, 4.1%; and group 3, 9.2%, P < 0.001). A new scoring system (R-CHA2 DS2 -VASc score) derived by assigning one more point for eGFR ≤ 60 mL/min per 1.73 m(2) to the CHA2 DS2 -VASc score could improve its predictive accuracy (area under the receiver operating curve, 0.70 vs. 0.66, P < 0.001). CONCLUSIONS: Renal dysfunction is a significant risk factor of future adverse events in ACS patients and may improve the prognostic impact of the CHA2 DS2 -VASc score.

Renal dysfunction and the risk of postoperative atrial fibrillation after cardiac surgery: role beyond the CHA2DS2-VASc score.

AIMS: To investigate whether renal dysfunction is a useful predictor of postoperative atrial fibrillation (POAF) after cardiac surgery. We also aimed to determine whether the addition of renal dysfunction into the scoring system could improve diagnostic accuracy of the CHA2DS2-VASc score to predict POAF. METHODS AND RESULTS: The study prospectively enrolled 350 consecutive patients who underwent cardiac surgery. Echocardiography was performed before cardiac surgery. Renal dysfunction was defined as estimated glomerular filtration rate < 60 mL min(-1) 1.73 m(-2). All patients were monitored with continuous electrocardiographic telemetry for the occurrence of POAF until the day of hospital dismissal. Postoperative atrial fibrillation occurred in 103 of 350 patients (29%). Patients with POAF was associated with longer intensive care unit stay compared with those without POAF (3.7 ± 2.2 vs. 3.1 ± 1.4 days, P = 0.002). Both the CHA2DS2-VASc score and renal dysfunction were independent predictors of POAF in multivariate analysis. Renal dysfunction can further stratify patients with a CHA2DS2-VASc score of 0 or 1 into two groups with different POAF rates (3.1% vs. 68.8%, P < 0.001). A new scoring system (R-CHA2DS2-VASc score) derived by assigning an additional point representing renal dysfunction to the CHA2DS2-VASc score could improve its predictive accuracy. The area under the receiver operating characteristic curve increased from 0.68 to 0.71 (P < 0.001). Furthermore, the rate of left ventricular diastolic dysfunction also increased with increasing renal dysfunction. CONCLUSION: Renal dysfunction, associated with left ventricular diastolic dysfunction, was a significant risk factor for POAF after cardiac surgery and may improve the diagnostic accuracy of the CHA2DS2-VASc score.

Prevalence and prognosis of Brugada electrocardiogram patterns in an elderly Han Chinese population: a nation-wide community-based study (HALST cohort).

AIMS: The exact world-wide prevalence of Brugada electrocardiogram (ECG) pattern is still unclear, especially in adults aged 55 years and older. METHODS AND RESULTS: The study was conducted as part of the Healthy Aging Longitudinal Study in Taiwan (HALST). Using a stratified random sampled method, a sample of community-dwelling subjects was recruited from seven community-based regions across Taiwan. All enrolled subjects were follow-up annually and cause of death was documented by citizen death records. A total of 5214 subjects were enrolled (male/female: 2530/2684) with a mean age of 69 ± 8 years. The overall prevalence of Brugada ECG patterns was 3.32%. Four subjects carried spontaneous Type 1 Brugada ECG pattern, 68 carried Type 2, and 101 carried Type 3. Compared with the world-wide average prevalence of Brugada ECG patterns, the prevalence of spontaneous Type 1 Brugada ECG pattern in subjects from the HALST cohort was similar (0.077 vs. 0.07%) and the combined prevalence of Types 2 and 3 Brugada ECG pattern was 10 times higher (3.24 vs. 0.28%) even the mean age of study subjects was significantly higher (69 ± 8 vs. 35 ± 8, P < 0.001). However, all-cause mortality and cardiac mortality rates were not significantly different between subjects with and without Brugada ECG patterns during the 4-year follow-up (log-rank test, P = 0.21, 0.32, respectively). CONCLUSION: The prevalence of Brugada ECG pattern in adults aged 55 years and older in Taiwan was higher than the average world-wide prevalence but was not associated with increased mortality.

Complete AV Block and Torsades de Pointes in a Case of Primary Cardiac T-Cell Lymphoma.

UNLABELLED: Primary cardiac lymphoma is very rare, and the most common electrocardiographic finding in this condition is complete atrioventricular block. After electrolytic, metabolic, ischemic, infectious, and traumatic etiologies have been excluded, primary cardiac lymphoma should be consided as a possible cause of reversible atrioventricular block. Most patients with primary cardiac lymphoma are immunocompromised and have disease with a B-cell etiology. This is the first case report of a primary cardiac T-cell lymphoma with complete atrioventricular block and torsades de pointes in an immunocompetent patient who was successfully treated using chemotherapy. KEY WORDS: Atrioventricular block; T-cell lymphoma; Torsades de pointes.

TNF-α induces CXCL1 chemokine expression and release in human vascular endothelial cells in vitro via two distinct signaling pathways.

AIM: Chemokines usually direct the movement of circulating leukocytes to sites of inflammation or injury. CXCL1/GRO-α has been shown to be upregulated in atherosclerotic lesions and various cancers. The aim of this study was to investigate the mechanisms underlying the TNF-α-induced release of CXCL1 from human vascular endothelial cells in vitro. METHODS: Human umbilical vein endothelial cells (HUVECs) were treated with different proinflam-matory mediators and growth factors. CXCL1 expression and secretion were determined using RT-PCR and ELISA, respectively. TNF-α-induced cell signaling was assayed with Western blotting. Cell viability/growth was determined using MTT assay. Monocyte migration was measured with transwell migration assay. RESULTS: Among the 17 mediators and growth factors tested, TNF-α, LPS and thrombin induced marked increase in CXCL1 release from HUVEC cells. TNF-α (2, 5 ng/mL) induced CXCL1 release and mRNA expression in the cells in concentration- and time-dependent manners. TNF-α (5 ng/mL) caused activation of JNK, p38 MAPK, PI3K and Akt, whereas pretreatment with JNK inhibitor (SP600125), p38 MAPK inhibitor (SB202190) or PI-3K inhibitor (LY294002) significantly suppressed TNF-α-induced CXCL1 release from the cells. But only SP600125 significantly reduced TNF-α-induced CXCL1 mRNA expression in the cells. Moreover, dexamethasone (up to 500 nmol/L) failed to affect TNF-α-induced CXCL1 release from the cells. In functional studies, recombinant CXCL1 enhanced HUVEC proliferation, and both recombinant CXCL1 and TNF-α-induced CXCL1 from HUVECs attracted human monocyte migration. CONCLUSION: TNF-α stimulates CXCL1 release from human ECs through JNK-mediated CXCL1 mRNA expression and p38 MAPK- and PI-3K-mediated CXCL1 secretory processes.

Gender and Age Differences in Short- and Long-Term Outcomes Following Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction.

BACKGROUND: Studies have reported that women with ST elevation myocardial infarction (STEMI) have worse short- and long-term outcomes than men. It has not yet been confirmed whether these differences reflect differences in age between men and women. METHODS: We retrospectively enrolled 1035 consecutive STEMI patients treated with primary percutaneous coronary intervention (PCI). Baseline clinical characteristics, coronary anatomy, and outcome were compared between young (< 65 years old) and older patients (≥ 65 years old) of both sexes. RESULTS: Younger women presented with a lower incidence of typical angina (83% vs. 93%, p = 0.03), single-vessel disease (21% vs. 35%, p = 0.03), and total occlusion of infarct-related artery (65% vs. 83%, p = 0.001) than younger men, with no gender difference noted in the older group. Younger women in the study had a higher incidence of reinfarction, heart failure requiring admission, or mortality (23% vs. 6%, p < 0.001) during follow-up, compared with younger men, with no gender difference in the older group. Using the Kaplan-Meier analysis, younger women had lower rates of event-free survival (p < 0.001 by log-rank test) than younger men, with no gender difference in the older group. In multivariate analysis, age could predict long-term outcome in men (Hazard ratio 4.43, 95% confidence interval: 2.89-6.78, p < 0.001) but not in women. CONCLUSIONS: In STEMI patients receiving primary PCI, sex-related long-term outcome differences were age-dependent, with younger women likely to have a worse long-term outcome when compared with younger men. KEY WORDS: Coronary heart disease; Gender; Myocardial infarction.

Association Between Renal Function, Diastolic Dysfunction, and Postoperative Atrial Fibrillation Following Cardiac Surgery.

Background: Renal dysfunction is associated with a higher rate of atrial fibrillation in clinical practice. This study investigated the associations between renal function, left ventricular (LV) diastolic dysfunction, and postoperative atrial fibrillation (POAF). Methods and Results: A total of 265 consecutive patients who underwent cardiac surgery were prospectively enrolled in the study. Echocardiography was performed before cardiac surgery. The patients were divided into 3 groups based on estimated glomerular filtration rate (eGFR) (group 1, ≥90ml·min-1·1.73m-2; group 2, 60-90ml·min-1·1.73m-2; and group 3, <60ml·min-1·1.73m-2). POAF occurred in 83 of 265 patients (31.3%). The rate of new-onset POAF increased from 15.2% (12/79) in group 1 to 27.8% (27/97) in group 2 and 49.4% (44/89) in group 3 (P<0.001). Further, with increasing renal dysfunction from groups 1 to 3, the rate of LV diastolic dysfunction - defined as E/e' >15 - also increased (group 1, 19.0%; group 2, 38.1%; and group 3, 48.3%; P<0.001). Absolute eGFR was significantly correlated with E/e' ratio (r=-0.39, P<0.001). Renal function remained as the independent predictor of POAF on multivariate analysis (odds ratio, 1.90; 95% confidence interval: 1.26-2.87; P=0.002). Conclusions: In patients undergoing cardiac surgery, decreased eGFR was associated with an increased rate of LV diastolic dysfunction with a subsequent increase in the rate of POAF.

Association between renal function, diastolic dysfunction, and postoperative atrial fibrillation following cardiac surgery.

BACKGROUND: Renal dysfunction is associated with a higher rate of atrial fibrillation in clinical practice. This study investigated the associations between renal function, left ventricular (LV) diastolic dysfunction, and postoperative atrial fibrillation (POAF). METHODS AND RESULTS: A total of 265 consecutive patients who underwent cardiac surgery were prospectively enrolled in the study. Echocardiography was performed before cardiac surgery. The patients were divided into 3 groups based on estimated glomerular filtration rate (eGFR) (group 1, ≥90ml·min(-1)·1.73m(-2); group 2, 60-90ml·min(-1)·1.73m(-2); and group 3, <60ml·min(-1)·1.73m(-2)). POAF occurred in 83 of 265 patients (31.3%). The rate of new-onset POAF increased from 15.2% (12/79) in group 1 to 27.8% (27/97) in group 2 and 49.4% (44/89) in group 3 (P<0.001). Further, with increasing renal dysfunction from groups 1 to 3, the rate of LV diastolic dysfunction - defined as E/e' >15 - also increased (group 1, 19.0%; group 2, 38.1%; and group 3, 48.3%; P<0.001). Absolute eGFR was significantly correlated with E/e' ratio (r=-0.39, P<0.001). Renal function remained as the independent predictor of POAF on multivariate analysis (odds ratio, 1.90; 95% confidence interval: 1.26-2.87; P=0.002). CONCLUSIONS: In patients undergoing cardiac surgery, decreased eGFR was associated with an increased rate of LV diastolic dysfunction with a subsequent increase in the rate of POAF.

Vascular endothelial growth factor induces CXCL1 chemokine release via JNK and PI-3K-dependent pathways in human lung carcinoma epithelial cells.

Lung cancer cells express different chemokines and chemokine receptors that modulate leukocyte infiltration within tumor microenvironment. In this study we screened several mediators/growth factors on CXCL1 release in human carcinoma epithelial cells. Of the tested mediators, VEGF was found to have a robust increase in causing CXCL1 release. VEGF stimulated CXCL1 release and mRNA expression in a time- and concentration-dependent manner. The release was inhibited by the VEGF receptor antagonists and the JNK, PI-3K, tyrosine kinase, and transcription inhibitors. In parallel, VEGF induced JNK, PI3K and Akt activation. Strikingly, among these inhibitors only the JNK inhibitor could reduce VEGF-induced CXCL1 mRNA expression, suggesting that JNK participated in VEGF-induced CXCL1 synthesis, whereas PI-3K was responsible for cellular CXCL1 secretory process. In addition, the steroid dexamethasone and TGF-ß suppressed CXCL1 release through a transcriptional regulation. We also showed that cells stimulated with VEGF significantly attracted monocyte migration, which could be abolished by CXCL1 B/N Ab, CXC receptor 2 antagonist, TGF-ß, and dexamethasone. In summary, we provide here evidence showing JNK activation for VEGF-induced CXCL1 DNA transcription and PI-3K pathway for extracellular CXCL1 release in human carcinoma epithelial cells. The released CXCL1 was functionally linked to recruiting monocytes into lung cancer cell microenvironment.

Diagnostic Performance of 64- versus 256-Slice Computed Tomography Coronary Angiography Compared with Conventional Coronary Angiography in Patients with Suspected Coronary Artery Disease.

PUPOSE: The newer 256-slice computed tomography coronary angiography (CTCA) has the capability of improving diagnostic performance in the detection of obstructive coronary artery disease (CAD) compared to 64-slice CTCA. The aim of this study was to compare the diagnostic performance of 64- versus 256-slice CTCA in two similar populations. METHODS: Our study included 120 consecutive patients who were referred for CTCA and subsequently underwent conventional coronary angiography (CCA). Sixty patients were studied by 64-slice CTCA, with the other 60 by 256-slice CTCA. We compared the technical characteristics and diagnostic performance of 64- and 256-slice CTCA for the detection of ≥ 50% stenosis of the coronary arteries on CCA. RESULTS: The 256-slice CTCA had a shorter scanning time (4.4 ± 0.6 sec vs. 5.0 ± 0.7 sec, p < 0.001) compared to 64-slice CTCA. The diagnostic accuracy rates of 256-slice CTCA based on patient analysis (97% vs. 83%, p < 0.05), vessel analysis (95% vs. 85%, p < 0.05), and segment analysis (94% vs. 88%, p < 0.05) were significantly superior to those of 64-slice CTCA. The diagnostic accuracy rates of 64- and 256-slice CTCA were affected by the presence of stent (65% vs. 75%, respectively, p > 0.05) and severe calcifications (75% vs. 82%, respectively, p > 0.05). CONCLUSIONS: In two similar populations, 256-slice CTCA displayed superior diagnostic performance than 64-slice CTCA. However, the performance of 256-slide CTCA is affected in those segments that are severely calcified and/or stented. KEY WORDS: Computed tomography coronary angiography (CTCA); Conventional coronary angiography; Diagnostic performance; 64-slice helical CTCA; 256-slice helical CTCA.

A naturally occurring carotenoid, lutein, reduces PDGF and H2O2 signaling and compromised migration in cultured vascular smooth muscle cells.

BACKGROUND: Platelet-derived growth factor (PDGF) is a potent stimulator of growth and motility of vascular smooth muscle cells (VSMCs). Abnormalities of PDGF/PDGF receptor (PDGFR) are thought to contribute to vascular diseases and malignancy. We previously showed that a carotenoid, lycopene, can directly bind to PDGF and affect its related functions in VSMCs. In this study we examined the effect of the other naturally occurring carotenoid, lutein, on PDGF signaling and migration in VSMCs. METHODS: Western blotting was performed to examine PDGF and H2O2 signaling. Flowcytometry was used to determine PDGF binding to VSMCs. Fluorescence microscopy was performed to examine intracellular ROS production. Modified Boyden chamber system (Transwell apparatus) was used for migration assay. RESULTS: Lutein reduced PDGF signaling, including phosphorylation of PDGFR-ß and its downstream protein kinases/enzymes such as phospholipase C-γ, Akt, and mitogen-activated protein kinases (MAPKs). Although lutein possesses a similar structure to lycopene, it was striking that lutein inhibited PDGF signaling through a different way from lycopene in VSMCs. Unlike lycopene, lutein not only interacted with (bound to) PDGF but also interfered with cellular components. This was evidenced that preincubation of PDGF with lutein and treatment of VSMCs with lutein followed by removing of lutein compromised PDGF-induced signaling. Lutein reduced PDGF-induced intracellular reactive oxygen species (ROS) production and attenuated ROS- (H2O2-) induced ERK1/2 and p38 MAPK activation. A further analysis indicated lutein could inhibit a higher concentration of H2O2-induced PDGFR signaling, which is known to act through an oxidative inhibition of protein tyrosine phosphatase. Finally, we showed that lutein functionally inhibited PDGF-induced VSMC migration, whereas its stereo-isomer zeaxanthin did not, revealing a special action of lutein on VSMCs. CONCLUSIONS: Our study reveals a differential action mechanism of lutein from other reported caroteinoids and suggests a possible beneficial effect of lutein but not zeaxanthin on prevention of vascular diseases.

The diagnostic accuracy of 256-row computed tomographic angiography compared with invasive coronary angiography in patients with suspected coronary artery disease.

AIMS: To assess the diagnostic accuracy of 256-row computed tomographic angiography (CTA) in patients with suspected coronary artery disease (CAD). Non-invasive imaging of the coronary artery by CTA has increasingly been used in recent years. The accuracy of 256-row CTA has not yet been studied. We sought to assess the accuracy of 256-row CTA compared with invasive coronary angiography (ICA) in the diagnosis and assessment of CAD. METHODS AND RESULTS: We prospectively evaluated 104 consecutive individuals who accepted CTA and then underwent ICA. The presence of stenosis > or =50% was considered obstructive. The diagnostic accuracy of CTA for detecting obstructive stenosis was compared with that of ICA. The area under the receiver-operating-characteristic curve (AUC) was used to evaluate the diagnostic accuracy of CTA relative to ICA. A total of 86 patients had obstructive CAD. The patient-based analysis of CTA for detecting stenosis > or =50% according to ICA revealed an AUC of 0.744 [95% confidence interval (CI), 0.572-0.916], with a sensitivity of 98.8%, a specificity of 50%, a positive predictive value (PPV) of 92.4%, and a negative predictive value (NPV) of 87.5%. The segment-based analysis revealed an AUC of 0.915 (95% CI, 0.847-0.982), with a sensitivity of 93.5%, a specificity of 95%, a PPV of 77.6%, and an NPV of 98.7%. The vessel-based analysis revealed an AUC of 0.887 (95% CI, 0.808-0.966), with a sensitivity of 94.3%, a specificity of 87.3%, a PPV of 82.7%, and an NPV of 95.9%. CONCLUSION: 256-Row CTA is a highly sensitive test of CAD and has a high predictive value. 256-Row CTA may be a potential alternative to detect coronary artery stenosis and rule out CAD in suspected patients.

Successful bailout stenting strategy against rare spontaneous retrograde dissection of partially absorbed magnesium-based resorbable scaffold: A case report.

BACKGROUND: In the development of coronary stent technology, bioresorbable scaffolds are promising milestones in improving the clinical treatment of coronary artery disease. The "leave nothing behind" motto is the premise of the fourth revolution in percutaneous coronary intervention (PCI). Studies proving the safety and efficacy of the magnesium-based resorbable scaffolds (MgBRSs) include the BIOSOLVE-I and BIOSOLVE-II trials and the latest BIOSOLVE-IV registry. However, spontaneous retrograde dissection of a partially absorbed MgBRS may still occur, albeit rarely. CASE SUMMARY: We describe an unusual case of coronary artery disease in a patient who had undergone a successful PCI 8 mo earlier, where an MgBRS was implanted into the left anterior descending artery (LAD) and left circumflex artery with drug-coated balloons for a ramus intermedius branch stenosis to achieve the "leave nothing behind" therapeutic intention and was currently presenting with a gradual worsening of chest tightness. The distal edge vascular response, during subsequent attempts with balloon angioplasty was performed smoothly. However, spontaneous retrograde dissection of a partially absorbed MgBRS in the LAD ensued. Successful bailout stenting was performed with revascularization of the entry and exit sites created by spontaneous dissection and complete sealing of the intramural hematoma. The patient recovered well and was discharged after 2 d of intervention. When followed up in August 2020 (7 mo later), the patient showed uneventful recovery. CONCLUSION: Spontaneous retrograde dissection of a partially absorbed MgBRS was successfully treated using bailout sirolimus-eluting coronary stent strategy.

Significance of left circumflex artery-related acute myocardial infarction without ST-T changes.

INTRODUCTION: Left circumflex (LC)-related acute myocardial infarction (AMI) presenting without ST-T changes has been underdiagnosed in the emergency department. There is little information on its clinical features and significance. AIMS: The aims of the study were to investigate the clinical characteristics and outcomes of LC-related AMI without ST-T changes. POPULATION AND METHODS: Ninety-six patients were admitted for LC-related AMI. Comparisons between those with and without ST-T changes were analyzed. RESULTS: Twenty-two patients (23%) did not have ST-T changes, whereas 74 patients (77%) had them. Patients without ST-T changes had younger age (55.6 + or - 16.8 vs 62.6 + or - 12.0 years, P = .03), fewer presented as Killip III/IV (4.5% vs 27.4%, P = .02) and with lower creatine kinase (1647.3 + or - 1602.2 vs 2778.2 + or - 2343.3 IU/L, P = .037) and creatine kinase-MB (136.8 + or - 130.3 vs 247.7 + or - 200.0 IU/L, P = .017), and more were with concurrent culprit lesion in the middle or distal LC and right- or balanced-dominant coronary circulation (86.4% vs 44.6%, P < .001). During follow-up, the need for repeat percutaneous coronary intervention (48.6% vs 45.5%, P = .40) and recurrent infarction (13.5% vs 13.6%, P = .62) were similar between the 2 groups. The 30-day mortality (0% vs 5.4%, P = .35) and overall mortality rate (4.5% vs 12.2%, P = .28) between them were not different statistically. CONCLUSION: The relatively lower prevalence of LC-related AMI without ST-T changes in the study might be underestimated. These patients have smaller infarct size than patients with ST-T changes without differences in the short- and long-term outcomes between them.