The relationship between miRNA-26b and connective tissue growth factor in rat models of aortic banding and debanding

Background/Aims@#Connective tissue growth factor (CTGF) is a profibrotic factor implicated in pressure overload-mediated myocardial fibrosis. In this study, we determined the role of predicted CTGF-targeting microRNAs (miRNAs) in rat models of aortic stenosis and reverse cardiac remodeling. @*Methods@#Minimally invasive ascending aortic banding was performed in 24 7-week-old male Sprague-Dawley rats, which were divided into three groups. The banding group consisted of eight rats that were sacrificed immediately after 6 weeks of aortic constriction. The debanding group underwent aortic constriction for 4 weeks and was sacrificed 2 weeks after band removal. The third group underwent sham surgery. We investigated the expression of CTGF, transforming growth factor-β1 (TGFβ1), and matrix metalloproteinase-2 using ELISA and examined miRNA-26b, miRNA-133a, and miRNA-19b as predicted CTGF-targeting miRNAs based on miRNA databases in 24-hour TGFβ-stimulated and TGFβ- washed fibroblasts and myocardial tissues from all subjects. @*Results@#CTGF was elevated in 24-hour TGFβ-stimulated fibroblasts and decreased in 24-hour TGFβ-washed fibroblasts. miRNA-26b was significantly increased in TGFβ-washed fibroblasts compared with control and TGFβ-stimulated fibroblasts (p < 0.05). CTGF expression was significantly higher in the banding group than that in the sham and debanding groups. The relative expression levels of miRNA-26b were higher in the debanding group than in the banding group. @*Conclusions@#The results of our study using models of aortic banding and debanding suggested that miRNA-26b was significantly increased after aortic debanding. The in vitro model yielded the same results: miRNA-26b was upregulated after removal of TGFβ from fibroblasts.

The relationship between miRNA-26b and connective tissue growth factor in rat models of aortic banding and debanding

Background/Aims@#Connective tissue growth factor (CTGF) is a profibrotic factor implicated in pressure overload-mediated myocardial fibrosis. In this study, we determined the role of predicted CTGF-targeting microRNAs (miRNAs) in rat models of aortic stenosis and reverse cardiac remodeling. @*Methods@#Minimally invasive ascending aortic banding was performed in 24 7-week-old male Sprague-Dawley rats, which were divided into three groups. The banding group consisted of eight rats that were sacrificed immediately after 6 weeks of aortic constriction. The debanding group underwent aortic constriction for 4 weeks and was sacrificed 2 weeks after band removal. The third group underwent sham surgery. We investigated the expression of CTGF, transforming growth factor-β1 (TGFβ1), and matrix metalloproteinase-2 using ELISA and examined miRNA-26b, miRNA-133a, and miRNA-19b as predicted CTGF-targeting miRNAs based on miRNA databases in 24-hour TGFβ-stimulated and TGFβ- washed fibroblasts and myocardial tissues from all subjects. @*Results@#CTGF was elevated in 24-hour TGFβ-stimulated fibroblasts and decreased in 24-hour TGFβ-washed fibroblasts. miRNA-26b was significantly increased in TGFβ-washed fibroblasts compared with control and TGFβ-stimulated fibroblasts (p < 0.05). CTGF expression was significantly higher in the banding group than that in the sham and debanding groups. The relative expression levels of miRNA-26b were higher in the debanding group than in the banding group. @*Conclusions@#The results of our study using models of aortic banding and debanding suggested that miRNA-26b was significantly increased after aortic debanding. The in vitro model yielded the same results: miRNA-26b was upregulated after removal of TGFβ from fibroblasts.

Long-term Survival in Korean Elderly Patients with Symptomatic Severe Aortic Stenosis Who Refused Aortic Valve Replacement

BACKGROUND AND OBJECTIVES@#Aortic valve replacement (AVR) is the treatment of choice in severe symptomatic aortic stenosis (AS) patients. However, a substantial number of elderly patients refuse AVR and treated medically. We investigated their long-term prognosis.@*METHODS@#From January 2005 to December 2016, we analyzed elderly patients with severe symptomatic AS who refused to have AVR.@*RESULTS@#After screening of total 534 patients, we analyzed total 180 severe symptomatic AS patients (78±7 years old, 96 males). Hypertension was the most common cardiovascular risk factor (72%) and the most common symptom was dyspnea (66%). Calculated aortic stenosis area was 0.73±0.20 cm2 and mean left ventricular ejection fraction (LVEF) was 57.8±12.2%. Total 102 patients died during follow-up period (39.1±31.0 months). One-, 3-, and 5-year all-cause mortality rate was 21.1±3.0%, 43.1±3.8%, and 56.5±4.2%, respectively. Of them, 87 died from cardiac causes, and 1-, 3-, and 5-year cardiac mortality rate was 18.0±2.9%, 38.2±3.8%, and 50.7±4.3%, respectively. Their all-cause mortality and cardiac mortality were significantly higher than those of controls. Univariate analysis showed that age, anemia, LVEF, and Log N-terminal pro B-type natriuretic peptide (NT-proBNP) were significant parameters in all-cause mortality (p < 0.001, p=0.001, p=0.039, and p=0.047, respectively) and in cardiac mortality (p < 0.001, p < 0.001, p=0.046, and p=0.026, respectively). Multivariate analysis showed that age and anemia were significant prognostic factors for cardiac and all-cause mortality.@*CONCLUSIONS@#In elderly severe symptomatic AS patients who treated medically, their 1-, 3- and 5-year all-cause mortality rate was 21.1±3.0%, 43.1±3.8%, and 56.5±4.2%, respectively. Age and anemia were significant prognostic factors for cardiac and all-cause mortality.

Long-term Survival in Korean Elderly Patients with Symptomatic Severe Aortic Stenosis Who Refused Aortic Valve Replacement

BACKGROUND AND OBJECTIVES: Aortic valve replacement (AVR) is the treatment of choice in severe symptomatic aortic stenosis (AS) patients. However, a substantial number of elderly patients refuse AVR and treated medically. We investigated their long-term prognosis. METHODS: From January 2005 to December 2016, we analyzed elderly patients with severe symptomatic AS who refused to have AVR. RESULTS: After screening of total 534 patients, we analyzed total 180 severe symptomatic AS patients (78±7 years old, 96 males). Hypertension was the most common cardiovascular risk factor (72%) and the most common symptom was dyspnea (66%). Calculated aortic stenosis area was 0.73±0.20 cm2 and mean left ventricular ejection fraction (LVEF) was 57.8±12.2%. Total 102 patients died during follow-up period (39.1±31.0 months). One-, 3-, and 5-year all-cause mortality rate was 21.1±3.0%, 43.1±3.8%, and 56.5±4.2%, respectively. Of them, 87 died from cardiac causes, and 1-, 3-, and 5-year cardiac mortality rate was 18.0±2.9%, 38.2±3.8%, and 50.7±4.3%, respectively. Their all-cause mortality and cardiac mortality were significantly higher than those of controls. Univariate analysis showed that age, anemia, LVEF, and Log N-terminal pro B-type natriuretic peptide (NT-proBNP) were significant parameters in all-cause mortality (p < 0.001, p=0.001, p=0.039, and p=0.047, respectively) and in cardiac mortality (p < 0.001, p < 0.001, p=0.046, and p=0.026, respectively). Multivariate analysis showed that age and anemia were significant prognostic factors for cardiac and all-cause mortality. CONCLUSIONS: In elderly severe symptomatic AS patients who treated medically, their 1-, 3- and 5-year all-cause mortality rate was 21.1±3.0%, 43.1±3.8%, and 56.5±4.2%, respectively. Age and anemia were significant prognostic factors for cardiac and all-cause mortality.

Current Awareness and Use of the Strain Echocardiography in Routine Clinical Practices: Result of a Nationwide Survey in Korea

BACKGROUND: Because conventional echocardiographic parameters have several limitations, strain echocardiography has often been introduced in clinical practice. However, there are also obstacles in using it in clinical practice. Therefore, we wanted to find the current status of awareness on using strain echocardiography in Korea. METHODS: We conducted a nationwide survey to evaluate current use and awareness of strain echocardiography from the members of the Korean Society of Echocardiography. RESULTS: We gathered total 321 questionnaires from 25 cardiology centers in Korea. All participants were able to perform or interpret echocardiographic examinations. All participating institutions performed strain echocardiography. Most of our study participants (97%) were aware of speckle tracking echocardiography and 185 (58%) performed it for clinical and research purposes. Two-dimensional strain echocardiography was the most commonly used modality and left ventricle (LV) was the most commonly used cardiac chamber (99%) for clinical purposes. Most of the participants (89%) did not think LV strain can replace LV ejection fraction (LVEF) in their clinical practice. The common reasons for not performing routine use of strain echocardiography was diversity of strain measurements and lack of normal reference value. Many participants had a favorable view of the future of strain echocardiography. CONCLUSION: Most of our study participants were aware of strain echocardiography, and all institutions performed strain echocardiography for clinical and research purposes. However, they did not think the LV strain values could replace LVEF. The diversity of strain measurements and lack of normal reference values were common reasons for not using strain echocardiography in clinical practice.

Antiallergic Effects of Trichostatin A in a Murine Model of Allergic Rhinitis

OBJECTIVES: Trichostatin A (TSA), an inhibitor of histone deacetylase, has been shown to play an important role in attenuating asthmatic inflammation. However, the effect of TSA in allergic rhinitis is not known. The aims of this study were to investigate the effect of TSA on allergic nasal inflammation and on the induction of regulatory T cells in a murine model of allergic rhinitis. METHODS: BALB/c mice were sensitized intraperitoneally with ovalbumin (OVA) and then challenged intranasally with OVA. TSA (1 mg/kg) was given to the treatment group, and multiple parameters of allergic responses were evaluated to determine the effects of TSA on allergic rhinitis. Allergic nasal symptom scores, including frequency of rubbing and sneezing, were checked. Eosinophil infiltrations were stained with Chromotrope 2R, and the expression levels of OVA-specific IgE, T-helper 1 (Th1) cytokine (interferon-gamma [IFN-gamma]), Th2 cytokines (interleukin [IL] 4 and IL-5) and Treg (Foxp3, IL-10, and transforming growth factor-beta [TGF-beta]) were measured by quantitative reverse transcription-polymerase chain reaction or enzyme-linked immunosorbent assay. RESULTS: TSA reduced the scores of allergic nasal symptoms and the amount of eosinophil infiltration into the nasal mucosa. TSA suppressed OVA-specific IgE levels and reduced expression of the IL-4 and IL-5. However, the expression of IFN-gamma was unchanged in the treatment group. The levels of Foxp3, IL-10, and TGF-beta were increased in pretreatment with TSA as compared to control group. CONCLUSION: This study shows that TSA induced antiallergic effects by decreasing eosinophilic infiltration and Th2 cytokines in a murine model of allergic rhinitis via regulation of Tregs. Thus, TSA may be considered a potentially therapeutic agent in treating allergic rhinitis.

The Prognostic Value of the Left Ventricular Ejection Fraction Is Dependent upon the Severity of Mitral Regurgitation in Patients with Acute Myocardial Infarction

The prognostic value of the left ventricle ejection fraction (LVEF) after acute myocardial infarction (AMI) has been questioned even though it is an accurate marker of left ventricle (LV) systolic dysfunction. This study aimed to examine the prognostic impact of LVEF in patients with AMI with or without high-grade mitral regurgitation (MR). A total of 15,097 patients with AMI who received echocardiography were registered in the Korean Acute Myocardial Infarction Registry (KAMIR) between January 2005 and July 2011. Patients with low-grade MR (grades 0-2) and high-grade MR (grades 3-4) were divided into the following two sub-groups according to LVEF: LVEF 40% (n = 12,252 and 226, respectively). The primary endpoints were major adverse cardiac events (MACE), cardiac death, and all-cause death during the first year after registration. Independent predictors of mortality in the multivariate analysis in AMI patients with low-grade MR were age > or = 75 yr, Killip class > or = III, N-terminal pro-B-type natriuretic peptide > 4,000 pg/mL, high-sensitivity C-reactive protein > or = 2.59 mg/L, LVEF 40% were noted. MR is a predictor of a poor outcome regardless of ejection fraction. LVEF is an inadequate method to evaluate contractile function of the ischemic heart in the face of significant MR.

Inhibitory Effect of Delphinidin on Extracellular Matrix Production via the MAPK/NF-kappaB Pathway in Nasal Polyp-Derived Fibroblasts

PURPOSE: Nasal polyps are associated with chronic inflammation of the mucous membranes in the nose and paranasal sinuses and involved in extracellular matrix (ECM) accumulation. Delphinidin promotes ECM degradation in hepatitis and cardiac fibrosis. The aims of this study were to examine the inhibitory effect of delphinidin on TGF-beta1-induced myofibroblast differentiation and ECM accumulation, and to determine the underlying mechanisms in nasal polyp-derived fibroblasts (NPDFs). METHODS: NPDFs were stimulated with TGF-beta1, with or without delphinidin, and the expression levels of alpha-SMA, fibronectin, and collagen type I were determined by RT-PCR, Western blot analysis, and collagen assay. The expression of alpha-SMA protein was measured by immunocytochemical staining. Mitogen-activated protein kinase and NF-kappaB activation induced by TGF-beta1 were determined by Western blot analysis. The transcriptional activity of NF-kappaB was measured by luciferase assay. RESULTS: The expression levels of alpha-SMA, fibronectin, and collagen type I increased in TGF-beta1-stimulated NPDFs. In TGF-beta1-induced NPDFs, delphinidin inhibited the expression of alpha-SMA, fibronectin, and collagen. Inhibitors of MAPK and NF-kappaB blocked the expression of alpha-SMA, fibronectin, and collagen type I. Delphinidin suppressed the activation of MAPK and NF-kappaB induced by TGF-beta1 stimulation. CONCLUSIONS: These results suggest that delphinidin may inhibit TGF-beta1-induced myofibroblast differentiation and ECM production through the MAPK/NF-kappaB signaling pathway in NPDFs.

Sublingual Immunotherapy in Asian Children: 2-Year Follow-Up Results

BACKGROUNDS: House-dust mites are the main cause of allergic rhinitis in Asia, for which immunotherapy (SLIT) is a currently accepted treatment. However, few studies have evaluated the efficiency of SLIT on Asian children with allergic rhinitis for a period longer than one year. The aim of this study was to investigate the efficacy and safety of SLIT for Asian children with allergic rhinitis due to house-dust mites over a 2-year period. MATERIALS AND METHODS: This study included 65 patients who had allergic rhinitis due to Dermatophagoides pteronyssinus and Dermatophagoides farinae. All patients were treated with SLIT (Staloral(R)). Symptom scores and quality of life were evaluated by using questionnaires over two years. The medication score was assessed monthly by a diary medication card and serologic tests were evaluated before and two years after the start of treatment. Adverse effects and dropout rates were also investigated. RESULTS: All nasal and non-nasal symptoms and quality of life were significantly improved after two years of treatment. Furthermore, the total medication score decreased significantly and the serologic tests showed a significant change two years after the start of SLIT. Although minor adverse effects were reported, no systemic reactions were observed. The dropout rate was 40%. CONCLUSION: SLIT is an efficient and safe therapeutic tool for a period of two years in Asian children with allergic rhinitis to house-dust mites.

Role of Caffeic Acid on Collagen Production in Nasal Polyp-Derived Fibroblasts

OBJECTIVES: Caffeic acids are known to have anti-oxidant, anti-inflammatory, immunomodulatory, and tissue reparative effects. The purposes of this study were to determine the effect of caffeic acid on transforming growth factor (TGF) beta1-induced myofibroblast differentiation and collagen production, and to determine whether caffeic acid is involved in the antioxidant effect in nasal polyp-derived fibroblasts (NPDFs). METHODS: NPDFs were pretreated with caffeic acid (1-10 microM) for 2 hours and stimulated with TGF-beta1 (5 ng/mL) for 24 hours. The expression of alpha-smooth muscle actin (SMA), collagen types I and III, and Nox4 mRNA was determined by a reverse transcription-polymerase chain reaction, and the expression of alpha-SMA protein was determined by actin ned by immunofluorescence microscopy. The amount of total soluble collagen production was analyzed by the Sircol collagen dye-binding assay. The reactive oxygen species (ROS) generated by NPDFs were determined using 2',7'-dichlorfluorescein-diacetate. siNox4 was used to determine the effect of Nox4. RESULTS: The expression of alpha-SMA and production of collagen were significantly increased following TGF-beta1 treatment. In contrast, the level of expression of alpha-SMA and the level of production of collagen were decreased by pretreatment with caffeic acid. The activation of Nox4 and the subsequent production of ROS were also reduced by pretreatment with caffeic acid. The expression of alpha-SMA was prevented by inhibition of ROS generation with siNox4. CONCLUSION: Caffeic acid may inhibit TGF-beta1-induced differentiation of fibroblasts into myofibroblasts and collagen production by regulating ROS.

A Randomized, Multi-Center, Single Blind, Active-Controlled, Matched Pairs Clinical Study to Evaluate Prevention of Adhesion Formation and Safety of HyFence in Patients After Endoscopic Sinus Surgery

OBJECTIVES: Recurrent mucosal disease and anatomic obstruction are commonly cited causes of failed endoscopic sinus surgery (ESS). Hyaluronic acid (HA) has been reported to reduce scarring and to promote wound healing in sinonasal surgery. HyFence is HA stabilized by 1, 4-butandiol diglycidyl ether, which makes it less-water-soluble and highly viscoelastic. The purpose of this study is to examine the anti-adhesion effect of HyFence after ESS compared to that of HA-CMC (Guardix-Sol). METHODS: Seventy-four patients with chronic rhinosinusitis who underwent ESS were included in the study. After the ESS procedure, Merocel was placed in the ethmoidectomized areas of the both sides. Five milliliters of Guardix-Sol was then applied to the Merocel of one side and HyFence LV was applied to the other side. The effect of the agents was evaluated at one, two, and four weeks after surgery by endoscopic examination. The severity of adhesion, edema, infection and complications were evaluated. RESULTS: There was no significant difference in the incidence of postoperative adhesion between the HyFence group and the Guardix-Sol group (P>0.05). Mean postoperative grades of edema and infection showed no significant difference between groups (P>0.05). There was no significant postoperative complications associated with either anti-adhesion agent (P>0.05). CONCLUSION: HyFence has equivalent anti-adhesion effect compared to Guardix-Sol following ESS.

Prostaglandin E2 Induces IL-6 and IL-8 Production by the EP Receptors/Akt/NF-kappaB Pathways in Nasal Polyp-Derived Fibroblasts

PURPOSE: Interleukin 6 (IL-6) and IL-8 participate in the pathogenesis of chronic rhinosinusitis with nasal polyps, and their levels are increased by prostaglandin E2 (PGE2) in different cell types. The purposes of this study were to determine whether PGE2 has any effect on the increase in the levels of IL-6 and IL-8 in nasal polyp-derived fibroblasts (NPDFs) and subsequently investigate the possible mechanism of this effect. METHODS: Different concentrations of PGE2 were used to stimulate NPDFs at different time intervals. NPDFs were treated with agonists and antagonists of E prostanoid (EP) receptors. To determine the signaling pathway for the expression of PGE2-induced IL-6 and IL-8, PGE2 was treated with Akt and NF-kappaB inhibitors in NPDFs. Reverse transcription-polymerase chain reaction for IL-6 and IL-8 mRNAs was performed. IL-6 and IL-8 levels were measured byenzyme-linked immunosorbent assay (ELISA). The activation of Akt and NF-kappaB was evaluated by western blot analysis. RESULTS: PGE2 significantly increased the mRNA and protein expression levels of IL-6 and IL-8 in NPDFs. The EP2 and EP4 agonists and antagonists induced and inhibited IL-6 expression. However, the EP4 agonist and antagonist were only observed to induce and inhibit IL-8 expression level. The Akt and NF-kappaB inhibitors significantly blocked PGE2-induced expression of IL-6 and IL-8. CONCLUSIONS: PGE2 increases IL-6 expression via EP2 and EP4 receptors, and IL-8 expression via the EP4 receptor in NPDFs. It also activates the Akt and NF-kappaB signal pathways for the production of IL-6 and IL-8 in NPDFs. These results suggest that signaling pathway for IL-6 and IL-8 expression induced by PGE2 might be a useful therapeutic target for the treatment of nasal polyposis.

Histamine Promotes the Release of Interleukin-6 via the H1R/p38 and NF-kappaB Pathways in Nasal Fibroblasts

PURPOSE: Based on the close relationship between histamine and interleukin 6 (IL-6), we hypothesized that histamine may regulate the production of cytokines, such as IL-6, during allergic inflammation. Here, we examined the role of histamine in IL-6 production and histamine receptor activity in nasal fibroblasts, along with the mechanisms underlying these effects. METHODS: Experiments were performed using nasal fibroblasts from 8 normal patients. RT-PCR was used to identify the major histamine receptors expressed in nasal fibroblasts. Fibroblasts were then treated with histamine with or without histamine-receptor antagonists, and monitored for IL-6 production using an ELISA. Four potential downstream signaling molecules, p38, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and NF-kappaB, were evaluated by Western blot, and a luciferase reporter assay. RESULTS: Elevated expression was seen for all histamine receptors, with IL-6 protein levels increasing significantly following histamine stimulation. Among the histamine-receptor specific antagonists, only the H1R antagonist significantly decreased IL-6 production in histamine-stimulated nasal fibroblasts. Histamine increased the expression level of phosphorylated p38 (pp38), pERK, and pJNK, as well as NF-kappaB induction. The H1R antagonist actively suppressed pp38 and NF-kappaB expression in histamine-induced nasal fibroblasts, but not pERK and pJNK. The p38 inhibitor strongly attenuated IL-6 production in histamine-stimulated nasal fibroblasts. CONCLUSIONS: The data presented here suggest that antihistamines may be involved in the regulation of cytokines, such as IL-6, due to the role of histamine as an inflammatory mediator in nasal fibroblasts.

Myocardial Mechanics in a Rat Model with Banding and Debanding of the Ascending Aorta

BACKGROUND: Aortic banding and debanding models have provided useful information on the development and regression of left ventricular hypertrophy (LVH). In this animal study, we aimed to evaluate left ventricular (LV) deformation related to the development and regression of LVH. METHODS: Minimally invasive ascending aorta banding was performed in rats (10 Sprague Dawley rats, 7 weeks). Ten rats underwent a sham operation. Thirty-five days later, the band was removed. Echocardiographic and histopathologic analysis was assessed at pre-banding, 35 days of banding and 14 days of debanding. RESULTS: Banding of the ascending aorta created an expected increase in the aortic velocity and gradient, which normalized with the debanding procedure. Pressure overload resulted in a robust hypertrophic response as assessed by gross and microscopic histology, transthoracic echocardiography [heart weight/tibia length (g/m); 21.0 +/- 0.8 vs. 33.2 +/- 2.0 vs. 26.6 +/- 2.8, p < 0.001]. The circumferential (CS) and radial strains were not different between the groups. However, there were significant differences in the degree of fibrosis according to the banding status (fibrosis; 0.10 +/- 0.20% vs. 5.26 +/- 3.12% vs. 4.03 +/- 3.93%, p = 0.003), and global CS showed a significant correlation with the degree of myocardial fibrosis in this animal model (r = 0.688, p = 0.028). CONCLUSION: In this animal study, simulating a severe LV pressure overload state, a significant increase in the LV mass index did not result in a significant reduction in the LV mechanical parameters. The degree of LV fibrosis, which developed with pressure overload, was significantly related to the magnitude of left ventricular mechanics.

Effect of Prostaglandin E2 on Vascular Endothelial Growth Factor Production in Nasal Polyp Fibroblasts

PURPOSE: Angiogenesis is involved in the pathogenesis of chronic rhinosinusitis with nasal polyps. We aimed to investigate the effects of prostaglandin E2 (PGE2) on vascular endothelial growth factor (VEGF) production, the role of E-prostanoid (EP) 4 receptors, and the signal transduction pathway mediating VEGF production in nasal polyp-derived fibroblasts (NPDFs). METHODS: Eight primary NPDF cultures were established from nasal polyps, which were incubated with or without PGE2. Reverse transcription-polymerase chain reaction amplification of EP receptors (EP1, EP2, EP3, and EP4) and immunofluorescence staining for VEGF production were performed. VEGF production via the cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) and phosphatidylinositol 3-kinase (PI3K) pathways was evaluated by enzyme-linked immunosorbent assay. RESULTS: All EP receptors were expressed in NPDFs. PGE2 significantly increased VEGF production concentration- and time dependently, and VEGF production was regulated by an EP4 receptor. Activation of intracellular cAMP regulated VEGF production. VEGF production was decreased by PKA and PI3K inhibitors via intracellular cAMP. CONCLUSIONS: PGE2 stimulates VEGF production via the EP4 receptor in NPDFs. These results indicate that PGE2-induced VEGF production is mediated, at least partially, through cAMP-dependent signaling pathways. Therapies targeting the EP4 receptor may be effective in inhibiting the development of nasal polyps.

A Case of Three Consecutive Events of Acute Myocardial Infarctions in Three Different Vessels

A 51-year-old man was being admitted to the emergency department with chest pains. He had a history of acute myocardial infarction (MI) on two prior occasions and was successfully treated with drug eluting stents. He was diagnosed with 3 consecutive events of acute MI in 3 different vessels. The consecutive events of acute MI in different vessels are a very rare case. He did not have risk factors, such as coagulation abnormality, clopidogrel resistance, patient's compliance and vessel abnormality, except for his cigarette smoking. We reported the first case with 3 consecutive events of acute MI in each 3 vessels during a long-term interval.

Feasibility of Real-Time Three-Dimensional Echocardiography for the Assessment of Distorted Biventricular Systolic Function in Patients with Cor Pulmonale

BACKGROUND: This study was to investigate the feasibility of real-time 3-dimensional echocardiography (RT3DE) for the analysis of biventricular ejection fractions and volume measurements in patients with cor pulmonale and the correlations of RT3DE results with 64-slice multi-detector cardiac computed tomography (64-MDCT) results. METHODS: This study included a total of 22 patients (59.3 +/- 16.6 years of age; 10 males and 12 females) who showed flattening or reverse curvature of the interventricular septum and severe pulmonary hypertension [mean right ventricular (RV) systolic pressure = 66.8 +/- 19.7 mmHg] on 2-dimensional transthoracic echocardiography due to cor pulmonale. Biventricular end-diastolic and end-systolic volumes were measured by RT3DE and 64-MDCT. The severity of D-shaped deformation was evaluated by using left ventricular (LV) eccentricity index (ratio of diameters parallel/perpendicular to the interventricular septum on parasternal short axis images of the papillary muscle level). RESULTS: There were moderate correlations between biventricular volumes measured by RT3DE and 64-MDCT except for LV end-systolic volume (59.8 +/- 17.1 vs. 73.2 +/- 20.2 mL, r = 0.652, p = 0.001 for LV end-diastolic volume; 30.6 +/- 9.1 vs. 30.8 +/- 12.5 mL, r = 0.361, p = 0.099 for LV end-systolic volume; 110.1 +/- 42.9 vs. 171.1 +/- 55.3 mL, r = 0.545, p = 0.009 for RV end-diastolic volume; and 80.9 +/- 35.0 vs. 128.7 +/- 45.1 mL, r = 0.549, p = 0.005 for RV end-systolic volume respectively). CONCLUSION: This study suggests that RT3DE may be a modest method for measuring distorted biventricular end-systolic and end-diastolic volumes in patients with cor pulmonale.

Effects of Percutaneous Coronary Intervention on Depressive Symptoms in Chronic Stable Angina Patients

OBJECTIVE: Depression is present in 1 of 5 outpatients with coronary artery disease (CAD), and a well-documented risk factor for recurrent cardiac events and mortality. We examined the impact of percutaneous coronary intervention (PCI), on depressive symptoms, in chronic stable angina (CSA) patients. METHODS: On prospective and non-randomized trial, consecutive CSA patients (n=171), who had undergone coronary angiography from January 2006 to December 2007, were included. Patients were subdivided into PCI and non-PCI groups, and then completed 21-item the Beck Depression Inventory II (BDI-II), at the baseline and pre-discharge, to assess the depressive symptoms. RESULTS: A total of 108 (63%) patients were assigned to the non-PCI group, and 63 (37%) patients to the PCI group. Using an independent t-test, we found that patients with PCI were significantly older (non-PCI vs. PCI; 57+/-11 vs. 64+/-10, years, p<0.001), had more joint disease (12.0 vs. 27.0%, p=0.013), more stroke history (5.6 vs. 17.5%, p=0.012) and higher incident of family history of cardiovascular disease (28.7 vs. 46.0%, p=0.025), but less religion (54.6 vs. 36.5%, p=0.002) and private health insurance (43.5 vs. 20.6%, p=0.002). The mean difference of BDI-II score between the baseline and pre-discharge was higher in patients with PCI (OR: 1.266; 95% CI: 1.146-1.398, p<0.001). CONCLUSION: In conclusion, PCI contributes independently to higher risk of developing depressive symptoms in CSA patients during hospitalization; Routine assessment and management of PCI related depressive symptoms are justified.

A Case of Patent Ductus Arteriosus with Congestive Heart Failure in a 80-Year-Old Man

Patent ductus arteriosus (PDA) is a rare clinical finding in adult patients. Considering the increase in cases of PDA discovered incidentally on echocardiograms at young ages, and the life-shortening effect of PDA, it is rare to diagnose PDA in old patients. We report a case of an 80-year-old patient who experienced symptoms of congestive heart failure showed findings suggestive of PDA in echocardiogram and confirmed the diagnosis through a cardiac catheterization and a coronary angiography. After percutaneous occlusion of PDA with an Amplatzer duct occlusion device, symptoms related to congestive heart failure improved.

A Butterfly-Shaped Primary Cardiac Lymphoma That Showed Bi-Atrial Involvement

We described here a patient who presented with symptoms of heart failure who was found to have severe bilateral impairment of atrioventricular inflow. Primary cardiac lymphoma (PCL) with extensive involvement of the two atria, pericardium and myocardium is an extremely rare tumor in immunocompetent patients. We report here a case of PCL in an immunocompetent patient with involvement of both atria and the atrial septum. The tumor had a butterfly shape. We could not do surgical excision because of the massive pericardiac invasion. The diagnosis was B-cell lymphoma and this was confirmed by the pericardiac biopsy.