Jung Chaee Kang

Curcumin attenuates inflammatory responses of TNF-alpha-stimulated human endothelial cells.

Curcumin, a yellow pigment of turmeric in curry, is reported to interfere with nuclear factor (NF)-κB. This study was designed to investigate the underlying pathway of antiinflammation of curcumin on endothelial cells. Human umbilical vein endothelial cells (HUVECs) were stimulated with 10 ng/mL tumor necrosis factor (TNF)-α. Curcumin blocked the activation of NF-κB by TNF-α. Curcumin also reduced the intracellular reactive oxygen species (ROS), monocyte adhesion, phosphorylation of c-Jun N-terminal kinase (JNK), p38, and signal transducer and activator of transcription (STAT)-3 in TNF-α-stimulated HUVECs. The expression of intracellular cell adhesion molecule (ICAM)-1, monocyte chemoattractant protein (MCP)-1, and interleukin (IL)-8 were attenuated by curcumin at both mRNA and protein level. Curcumin, however, did not affect the expression of TNF receptor I and II in TNF-α-stimulated HUVECs. We suggest that curcumin could contribute to protection against the adverse vascular effect of the proinflammatory response through the modulation of p38 and STAT-3 in addition to NF-κB and JNK in endothelial cells.

Preventive effects of the heparin-coated stent on restenosis in the porcine model.

The coronary stent reduces acute coronary arterial occlusion and late restenosis during and after coronary intervention. However, stent thrombosis and restenosis are still major limitations in the widespread use of the coronary stent. Local drug delivery using the heparin‐coated stent may be a new approach, which reduces the incidence of stent thrombosis and restenosis. In order to evaluate the effects of the heparin‐coated stent on stent restenosis, heparin‐coated stents were compared with control stents in a porcine coronary stent restenosis model. Stent overdilation injury (stent:artery = 1.3:1.0) was performed with bare Wiktor stents (group I, n = 10) and heparin‐coated Wiktor stents (group II, n = 20; HEPAMED, Medtronics) in porcine coronary arteries. Follow‐up quan‐titative coronary angiography (QCA) was performed at 4 weeks after stenting, and histo‐pathologic assessments of stented porcine coronary arteries were compared in both groups.

Value of Early Risk Stratification Using Hemoglobin Level and Neutrophil-to-Lymphocyte Ratio in Patients With ST-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

Complete blood count is the most widely available laboratory datum in the early in-hospital period after ST-elevation myocardial infarction (STEMI). We assessed the clinical utility of the combined use of hemoglobin (Hb) level and neutrophil-to-lymphocyte ratio (N/L) for early risk stratification in patients with STEMI. We analyzed 801 consecutive patients with STEMI treated with primary percutaneous coronary intervention (PCI) within 12 hours of onset of symptoms. Patients with cardiogenic shock or underlying malignancy were excluded, and 739 patients (63 ± 13 years, 74% men) were included in the final analysis. Patients were categorized into 3 groups using the median value of N/L (3.86) and the presence of anemia (Hb <13 mg/dl in men and <12 mg/dl in women); group I had low N/L and no anemia (n = 272), group II had low N/L and anemia, or high N/L and no anemia (n = 331), and group III had high N/L and anemia (n = 136). There were significant differences on clinical outcomes during 6-month follow-up among the 3 groups. Prognostic discriminatory capacity of combined use of Hb level and N/L was also significant in high-risk subgroups such as patients with advanced age, diabetes mellitus, multivessel coronary disease, low ejection fraction, and even in those having higher mortality risk based on Thrombolysis In Myocardial Infarction risk score. In a Cox proportional hazards model, after adjusting for multiple covariates, group III had higher mortality at 6 months (hazard ratio 5.6, 95% confidence interval 1.1 to 27.9, p = 0.036) compared to group I. In conclusion, combined use of Hb level and N/L provides valuable timely information for early risk stratification in patients with STEMI undergoing primary PCI.

Rosuvastatin suppresses the inflammatory responses through inhibition of c-Jun N-terminal kinase and Nuclear Factor-kappaB in endothelial cells.

Background: Rosuvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, has pleiotropic effects that are anti-inflammatory and antiatherothrombotic. It is important to understand the cardioprotective effects of rosuvastatin in order to optimize its additional advantages in the treatment and prevention of cardiovascular diseases. Methods: Human umbilical vein endothelial cells (HUVEC) were treated with tumor necrosis factor (TNF)-α (10 ng/mL) alone or with rosuvastatin (100 μM). The extent of inflammation was determined by U937 adhesion assay as well as analysis of the expression of intercellular adhesion molecule (ICAM)-1, monocyte chemoattractant protein (MCP)-1, interleukin (IL)-8, IL-6, cyclooxygenase (COX)-2, c-Jun N-terminal kinase (JNK), extracellular signal-regulated protein kinase (ERK), p38, and signal transducer and activator of transcription (STAT)-3. The activation of nuclear factor kappa B (NF-κB) was determined by Western blot. Results: Rosuvastatin decreased the extent of U937 adhesion to TNF-α-stimulated HUVEC. Rosuvastatin inhibited the expressions of ICAM-1, MCP-1, IL-8, IL-6, and COX-2 mRNA and protein levels. The activation of JNK and NF-κB was also blocked by rosuvastatin. The inhibitors of JNK, NF-κB, and STAT-3 produced a statistically significant decrease of the TNF-α induced U937 adhesion and IL-6 protein release. Conclusions: This study suggests that the anti-inflammatory activity of rosuvastatin is accompanied by the inhibition of JNK and NF-κB.

Plaque Characteristics in Culprit Lesions and Inflammatory Status in Diabetic Acute Coronary Syndrome Patients

OBJECTIVES The aim of this study was to assess the plaque characteristics in culprit lesions in diabetic patients with acute coronary syndrome (ACS). BACKGROUND Data of the relationship between diabetes mellitus and plaque characteristics in patients with ACS are lacking. METHODS We performed grayscale intravascular ultrasound (IVUS) analysis in 422 ACS patients and virtual histology (VH)-IVUS in 310 ACS patients. By subgroup analysis, 112 patients with acute myocardial infarction (AMI) with plaque ruptures also were evaluated. RESULTS In the diabetic subgroup, high-sensitivity C-reactive protein (hs-CRP) was significantly increased (p = 0.008), multivessel disease was more common (65% vs. 29%, p < 0.001), and plaque burden was greater (79.7 +/- 9.8 mm2 vs. 74.2 +/- 8.9 mm2, p < 0.001). In the subgroup analysis of 112 AMI patients with plaque ruptures, the presence of multiple plaque ruptures (60% vs. 29%, p = 0.001) and thrombus (72% vs. 52%, p = 0.032) were more common in diabetic group. Diabetes mellitus was the independent predictor of hs-CRP elevation (odds ratio [OR]: 3.030, 95% confidence interval [CI]: 1.204 to 7.623, p = 0.019), and multiple plaque ruptures (OR: 2.984, 95% CI: 1.311 to 6.792, p = 0.009) by multivariable analysis. In 310 VH-IVUS subsets, the absolute and percent necrotic core volumes were significantly greater (16.9 +/- 15.1 mm3 vs. 11.5 +/- 11.4 mm3, p < 0.001, and 17.3 +/- 9.4% vs. 13.7 +/- 7.5%, p < 0.001, respectively), and the presence of at least one thin-cap fibroatheroma (TCFA) (60% vs. 42%, p = 0.003) and multiple TCFAs (28% vs. 11%, p < 0.001) were more common in the diabetic group. Diabetes mellitus was the only independent predictor of TCFA by multivariable analysis (OR: 2.139, 95% CI: 1.266 to 3.613, p = 0.004). CONCLUSIONS Diabetic patients with ACS have more plaques with characteristics of plaque vulnerability, different composition of plaques, and have increased inflammatory status compared with nondiabetic patients with ACS.

Plaque Prolapse After Stent Implantation in Patients With Acute Myocardial Infarction: An Intravascular Ultrasound Analysis

OBJECTIVES The aim of this study was to assess the incidence, predictors, and outcome of plaque prolapse (PP) after stent implantation in acute myocardial infarction. BACKGROUND The imaging characteristics of PP in patients with acute myocardial infarction are not well known. METHODS Intravascular ultrasound (IVUS) imaging was performed in 310 patients immediately following stenting for their first acute myocardial infarction. Multiple clinical, angiographic and IVUS derived variables were compared among patients with and without intrastent PP. RESULTS The PP was detected in 27% of the 310 lesions examined. Stent length was longer (31 +/- 13 mm vs. 21 +/- 8 mm, p < 0.001), and positive remodeling (48% vs. 32%, p = 0.008), plaque rupture (51% vs. 31%, p = 0.001), and thrombus (40% vs. 21%, p = 0.001) were significantly more common in PP lesions compared with non-PP lesions. The creatine kinase-myocardial band (CK-MB) was significantly greater after stenting in PP lesions compared with non-PP lesions (Delta = +12.3 +/- 32.0 U/l vs. -4.9 +/- 46.1 U/l, p = 0.002). During a 1-month follow-up, the incidence of stent thrombosis was not significantly different between PP and non-PP lesions [2/85 (2.4%) vs. 2/225 (0.9%), p = 0.308]. Multivariate analysis showed that PP (odds ratio [OR]: 7.34, p < 0.001), plaque rupture (OR: 1.95, p = 0.023), and thrombus (OR: 1.84, p = 0.026) were independently associated with post-stenting CK-MB elevation, and stent length (OR: 2.39, p = 0.003), plaque rupture (OR: 1.96, p = 0.015), and positive remodeling (OR: 1.72, p = 0.044) were independently associated with the development of PP. CONCLUSIONS PP occurs in one-fourth of infarct-related arteries after stent implantation. Lesion characteristics such as plaque rupture and positive remodeling, together with longer stent predict PP. Although long-term follow-up is pending, PP is associated with more myonecrosis after stenting in patients with acute myocardial infarction.

Outcome of Undersized Drug-Eluting Stents for Percutaneous Coronary Intervention of Saphenous Vein Graft Lesions

We sought to determine the outcome with undersized drug-eluting stents for percutaneous coronary intervention of saphenous vein graft lesions. Using intravascular ultrasound guidance, 209 saphenous vein graft lesions were treated with drug-eluting stents (153 sirolimus-eluting and 56 paclitaxel-eluting stents). The lesions were divided into 3 groups according to the ratio of the stent diameter to the average intravascular ultrasound reference lumen diameter: group I, <0.89; group II, 0.9 to 1.0; and group III, >1.0. Angiographic no-reflow was defined as a Thrombolysis In Myocardial Infarction flow grade of 0, 1, and 2 after percutaneous coronary intervention. Plaque intrusion was defined as tissue extrusion through the stent struts. Stent malapposition was defined as one or more stent struts that had clearly separated from the vessel wall with evidence of blood speckles behind the strut. No significant differences were found in the use of distal protection devices (group I, 44%; group II, 35%; and group III, 36%; p = 0.5); and no significant differences were found in the incidence of stent malapposition among the 3 groups (group I, 21%; group II, 42%; and group III, 52%; p = 0.001). The plaque intrusion area (group I, 0.13 +/- 0.30 mm(2); group II, 0.25 +/- 0.42 mm(2); and group III, 0.31 +/- 0.40 mm(2); p = 0.018) and plaque intrusion volume (group I, 0.25 +/- 0.68 mm(3); group II, 0.40 +/- 0.68 mm(3); and group III, 0.75 +/- 1.34 mm(3); p = 0.007) were smallest in group I. The plaque intrusion area and plaque intrusion volume correlated with the ratio of the stent diameter to the average intravascular ultrasound reference lumen diameter (r = 0.278, p <0.001 and r = 0.283, p <0.001, respectively). The incidence of a creatine kinase-MB elevation >3 times normal was 6% in group I, 9% in group II, and 19% in group III (p = 0.025). No significant differences were found in the incidence of 1-year target lesion revascularization (group I, 13%; group II, 9%; and group III, 15%; p = 0.5) or target vessel revascularization (group I, 13%; group II, 13%; and group III, 15%; p = 0.9) among the 3 groups. In conclusion, the use of undersized drug-eluting stents to treat patients with saphenous vein graft lesions is associated with a reduction in the frequency of post-percutaneous coronary intervention creatine kinase-MB elevation without an increase in 1-year events.

Clinical outcomes and optimal treatment for stent fracture after drug-eluting stent implantation.

BACKGROUND Many studies have suggested that in the era of drug-eluting stents (DES) one of the causes of in-stent restenosis is stent fracture (SF). Yet there have been few studies of the major adverse cardiac events and treatment of DES SF. METHODS AND RESULTS From September 2003 to May 2008, 3365 patients received successful stent implantation with DES, of whom 1009 patients underwent a follow-up coronary angiography irrespective of symptoms. Seventeen SFs were detected in 15/1009 patients (1.5%). All SF patients were continued on medication with combination antiplatelet therapy, regardless of angina symptoms. If in-stent restenosis at the fractured site was significant, we performed coronary interventions even in patients without ischemic symptoms. Patients were treated with heterogenous DES for restenosis lesions (5/8 patients), and the rest were treated with either homogenous DES (2 patients), or plain old balloon angioplasty (1 patient) or medical treatment (7 patients). None of the SF patients suffered from cardiac death during a follow-up period of 20.4+/-12.3 months. CONCLUSION If patients with SF were continued on combination antiplatelet therapy irrespective of ischemic symptoms, there would occur a low rate of major adverse cardiac events, especially cardiac death associated with SF.

Usefulness of Aortic Strain Analysis by Velocity Vector Imaging as a New Echocardiographic Measure of Arterial Stiffness

BACKGROUND The role of velocity vector imaging (VVI) in evaluating arterial stiffness is not well known. We investigated the usefulness of vascular strain analysis by VVI in evaluating arterial stiffness. METHODS Heart-femoral and brachial-ankle pulse wave velocities (PWVs) were measured as standard parameters of arterial stiffness. Intima-media thickness (IMT), fractional shortening (FS), fractional area change (FAC) by two-dimensional (2D) and VVI methods, and peak circumferential strain (PS) of the descending thoracic aorta were measured as echocardiographic parameters of arterial stiffness and compared with PWV in 137 patients (53.8 +/- 13.4 years, 71 male). RESULTS Heart-femoral PWV was 9.0 +/- 2.4 m/s, and brachial-ankle PWV was 14.1 +/- 3.0 m/s. Aortic IMT was 0.97 +/- 0.23 mm, and FS was 10.0% +/- 4.0%. FAC was 10.9% +/- 5.2% by 2D tracing and 10.3% +/- 5.1% by the VVI method. PS was 5.4% +/- 3.0%. PS showed significant negative correlation with aortic IMT (r = -0.49, P < .01) and PWV (heart-femoral: r = -0.67, brachial-ankle: r = -0.75, P < .01). PS showed significant positive correlation with FS (r = 0.80, P < .01) and FAC (2D tracing: r = 0.86, VVI: r = 0.88, P < .01). Aortic IMT showed significant positive correlation with PWV (heart-femoral: r = 0.44, brachial-ankle: r = 0.60, P < .01) and negative correlation with FS (r = -0.61, P < .01) and FAC (2D tracing: r = -0.51, VVI: r = - 0.51, P < .01). FS showed significant negative correlation with PWV (heart-femoral: r = -0.54, brachial-ankle: r = -0.72, P < .01). FAC showed significant negative correlation with heart-femoral (2D method: r = -0.61, VVI: r = -0.62, P < .01) and brachial-ankle (2D tracing: r = -0.71, VVI: r = -0.73, P < .01) PWV. CONCLUSION PS and FAC measured by VVI were significantly associated with parameters of arterial stiffness and thus can be used as new echocardiographic parameters of arterial stiffness.

Carotid artery intima-media thickness in Behcet's disease patients without significant cardiovascular involvement

Background/Aims Behcets disease (BD) is a systemic disorder associated with a characteristic vasculitis that can involve both veins and arteries of all sizes. Endothelial activation or injury is a characteristic feature of BD. Endothelial dysfunction is widely regarded as being the initial lesion in the development of atherosclerosis. The carotid artery intima-media thickness (IMT) is a widely accepted marker of subclinical atherosclerosis. We aimed to determine the carotid IMT in BD patients with using high-resolution B-mode Doppler ultrasonography. Methods We studied 40 patients (24 males, mean age: 39.1±8.5 years) who were diagnosed by the international diagnostic criteria of Behcets disease and 20 healthy controls (13 males, mean age: 40.2±5.1 years), and the two groups were matched by age and gender. No subject in either group had a history of atherosclerosis or its complications. The clinical data, including the age of onset, the duration of disease, a history of medication, the activity score and the laboratory data were analyzed. Results The carotid IMT in the BD group was significantly higher than that in the control group (0.71±0.22 mm vs. 0.59±0.09 mm, respectively, p<0.01). Cardiac and major vessel involvements were not identified in the BD group. However, minor vascular involvements were documented in 2 patients with deep vein thrombosis, in 4 patients with superficial thrombophlebitis and in 2 patients with pseudoaneurysm. The carotid IMT in the patients with posterior uveitis or retinal vasculitis was higher than that of the patients without these findings (0.85±0.21 mm vs. 0.64±0.10 mm, respectively, p=0.007), but there was no difference of the IMT according to minor vascular involvement. Conclusions Despite that there was no significant cardiovascular involvement in the BD patients, the carotid IMT was significantly higher in the BD patients as compared with the healthy controls.