Jeong Gwan Cho

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.

Benefit of Early Statin Therapy in Patients With Acute Myocardial Infarction Who Have Extremely Low Low-Density Lipoprotein Cholesterol

OBJECTIVES We investigated whether statin therapy could be beneficial in patients with acute myocardial infarction (AMI) who have baseline low-density lipoprotein cholesterol (LDL-C) levels below 70 mg/dl. BACKGROUND Intensive lipid-lowering therapy with a target LDL-C value <70 mg/dl is recommended in patients with very high cardiovascular risk. However, whether to use statin therapy in patients with baseline LDL-C levels below 70 mg/dl is controversial. METHODS We analyzed 1,054 patients with AMI who had baseline LDL-C levels below 70 mg/dl and survived at discharge from the Korean Acute MI Registry between November 2005 and December 2007. They were divided into 2 groups according to the prescribing of statins at discharge (statin group n = 607; nonstatin group n = 447). The primary endpoint was the composite of 1-year major adverse cardiac events, including death, recurrent MI, target vessel revascularization, and coronary artery bypass grafting. RESULTS Statin therapy significantly reduced the risk of the composite primary endpoint (adjusted hazard ratio [HR]: 0.56; 95% confidence interval [CI]: 0.34 to 0.89; p = 0.015). Statin therapy reduced the risk of cardiac death (HR: 0.47; 95% CI: 0.23 to 0.93; p = 0.031) and coronary revascularization (HR: 0.45, 95% CI: 0.24 to 0.85; p = 0.013). However, there were no differences in the risk of the composite of all-cause death, recurrent MI, and repeated percutaneous coronary intervention rate. CONCLUSIONS Statin therapy in patients with AMI with LDL-C levels below 70 mg/dl was associated with improved clinical outcome.

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.

TNF-alpha enhances engraftment of mesenchymal stem cells into infarcted myocardium.

TNF-alpha released from ischemic heart after acute MI increases the production of other cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6) and adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1). Activation of nuclear factor kappa B (NF-kappa B) by TNF-alpha , up-regulates the expression of molecules which are involved in inflammation and cell adhesion. For these reasons, we assessed the extent that treatment of MSC with tumor necrosis factor (TNF)-alpha modifies the characteristics of MSC, important to their engraftment in experimental myocardial infarct. Here, we show that pre-treatment of MSC prior to transplantation with tumor necrosis factor (TNF)-alpha increases adhesiveness, and migration of MSC in vitro and leads to increased expression of bone morphogenetic protein (BMP)-2 by MSC. Moreover, this treatment increases the rate of engraftment of MSC and improves recovery of cardiac function after myocardial infarction. These insights might provide better strategies for the treatment of myocardial infarction.

Obesity paradox in Korean patients undergoing primary percutaneous coronary intervention in ST-segment elevation myocardial infarction

The effect of body mass index (BMI) on outcomes after primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) is not well known. In patients registered in the Korean Acute Myocardial Infarction Registry (KAMIR) between November 2005 and November 2007, 3824 STEMI patients who arrived at hospital within 12h after onset of chest pain and underwent primary PCI were analyzed, and divided into four groups according to their BMI: underweight (BMI<18.5 kg/m(2), n=129); normal weight (18.5 < or =BMI <23.0 kg/m(2), n=1253); overweight (23.0 < or =BMI <27.5 kg/m(2), n=1959); and obese (BMI > or =27.5 kg/m(2), n=483). In-hospital mortality, revascularization in 1 year, mortality in 1 year, and overall mortality were compared between groups. Overweight and obese group were significantly younger, had normal left ventricular ejection fraction, and were more likely to be men with a higher incidence of hypertension, diabetes, and hyperlipidemia. There were no significant differences in symptom-to-door time and door-to-balloon time between groups. Obese patients had significantly lower in-hospital and overall mortalities. Major adverse cardiac events showed a bimodal pattern. Obese STEMI patients treated with primary PCI were associated with lower mortality, which may be explained by better use of medical treatment, hemodynamic stability, and younger age.

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.

Are patients with angiographically near-normal coronary arteries who present as acute myocardial infarction actually safe?

BACKGROUND There is a paucity of data concerning the clinical outcome of patients presenting with acute myocardial infarction (AMI) and near-normal coronary angiograms. The purpose of this study was to evaluate the clinical outcome and the prognosis of the patients with near-normal coronary angiograms who were registered in the Korean Acute Myocardial Infarction Registry (KAMIR). METHODS The subjects were divided into three groups according to findings from coronary angiograms performed between September 2005 and November 2006. Among 8510 consecutive AMI patients, 372 patients (Group I) had near-normal coronary arteries, 6136 patients (Group II) had one- or two-vessel disease, and 2002 patients (Group III) had three-vessel or left main disease. RESULTS Clinical characteristics, in-hospital mortality, and major cardiac adverse events (MACE) were analyzed. Group I was younger, had the lower prevalence of DM, and showed the higher percentage of previous angina history compared to the other two groups. Group III showed a higher incidence of in-hospital mortality, but there was no significant difference between Group I and Group II (2.6% in Group II and 2.2% in Group I, p=0.952). Furthermore, MACE at 1 month, 6 months and 12 months revealed no significant difference between Groups I and II (12 month MACE: 7.8% in Group I and 12.2% in Group II, p=0.359). CONCLUSIONS Patients with near-normal coronary angiograms had similar clinical outcomes and prognosis compared with one- or two-vessel diseased patients presenting with an acute myocardial infarction.