Relation of circulating interleukin-6 to left ventricular remodeling in patients with reperfused anterior myocardial infarction

BACKGROUND: During the remodeling process after myocardial infarction (MI), the expression of proinflammatory cytokines is enhanced in the myocardium. However, only a few clinical studies have been conducted on cytokine involvement in left ventricular (LV) remodeling after MI. HYPOTHESIS: Circulating proinflammatory cytokines may be involved in LV remodeling in patients with reperfused MI. METHODS: We studied 25 patients with acute anterior MI who had undergone coronary reperfusion therapy, and 10 normal control subjects with no cardiac disease. In all patients, LV ejection fraction, end-diastolic volume index (EDVI), and end-systolic volume index (ESVI) were determined using left ventriculography at the acute phase and 6 months after onset. The delta EDVI and delta ESVI were calculated as the value of LV volume reduction, suggesting LV reverse remodeling. Serum levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha were measured using enzyme-linked immunosorbent assay. RESULTS: Serum levels of IL-6 and TNF-alpha at the acute phase were significantly higher in patients with MI than in control subjects (both p < 0.05). The IL-6 levels correlated well negatively with delta EDVI (r = 0.779, p = 0.039), whereas no correlation was found for TNF-alpha. According to multivariate analysis, IL-6 at the acute phase was a significant independent predictor for LV remodeling after reperfused MI (p = 0.007). CONCLUSIONS: Circulating IL-6 levels correlated closely with LV geometric changes during the remodeling process in patients with reperfused MI. Our study addresses the usefulness of another marker for LV remodeling after MI.     

Future medicine for hypertension in the elderly

The number of the aged patients with hypertension is now explosively increasing. In near future, progress of new and tailor-made prescribed antihypertensive drugs and curable-gene therapy for hypertension will improve new era of hypertension in the elderly. And finally, resolusion of the aging mechanism and anti-aging medicine may open our future.     

Computed tomography assessment of myocardial perfusion, viability, and function

In addition to coronary artery assessment, contrast-enhanced multidetector spiral computed tomography (CE-MDCT) can provide valuable information about myocardial perfusion. Using CE-MDCT, myocardial perfusion defects are often observed in the early phase of the contrast bolus (early defect (ED)), with residual defects (RDs) and late enhancement (LE) observed in the late phase in myocardial infarction (MI). However, the clinical significance of EDs, RDs, and LE has not yet been fully described. This work reviews myocardial viability and function by CE-MDCT based on our prior data by including contrast-enhanced single-slice (detector) CT (CE-SSCT) and CE-MDCT. Recently, equivalent results were obtained, as seen in CE-SSCT with images by CE-MDCT. In this review, images that were acquired by MDCT will be presented. In this work, the following items will be the focus: myocardial enhancement patterns (EDs, LE, and RDs), early perfusion defects and their relationship to wall thickness (WT) and wall motion, early CT perfusion defects vs. Tl-201 single photon emission CT (SPECT), the protocol for performing dual-phase contrast CT, classification of enhancement patterns, enhancement patterns on dual-phase CE-MDCT vs. left ventricular functional recovery and WT, changes in enhancement patterns in conjunction with healing stage, enhancement patterns on dual-phase CE-MDCT vs. 201Tl/99mTc-pyrophosphate (dual-isotope SPECT), the clinical meaning of each enhancement pattern, pitfalls of enhancement patterns and other diseases, and study limitations and the future of MDCT.     

Transforming growth factor-beta stimulates interleukin-11 production by human periodontal ligament and gingival fibroblasts

BACKGROUND: Transforming growth factor (TGF)-beta is a potent multifunctional polypeptide, abundant in the bone matrix. Interleukin (IL)-11 is a pleiotropic cytokine with effects on multiple cell types. The present study was performed to evaluate the regulatory effects of TGF-beta on IL-11 production by human periodontal ligament cells (PDL) and human gingival fibroblasts (HGF). MATERIAL AND METHODS: The expression of TGF-beta receptor in PDL and HGF were observed using flow cytometry. PDL and HGF were stimulated with TGF-beta with or without protein kinase C (PKC) inhibitors and activator. IL-11, bone morphogenetic protein-2 (BMP-2) and TGF-beta mRNA expression was quantified by real-time polymerase chain reaction (PCR). IL-11 production was measured using enzyme-linked immunosorbent assay. RESULTS: PDL and HGF expressed both TGF-beta receptor I and TGF-beta receptor II on the cell surfaces. IL-11 mRNA expression and IL-11 production were augmented by TGF-beta in both PDL and HGF, with higher values in PDL. PKC inhibitors partially suppressed TGF-beta-induced IL-11 production in PDL and HGF, whereas activator enhanced it. TGF-beta mRNA and BMP-2 mRNA expression were up-regulated by TGF-beta in PDL. CONCLUSION: These results suggest that PDL produce IL-11 in response to TGF-beta.     

Serum matrix metalloproteinase-3 as a novel marker for risk stratification of patients with nonischemic dilated cardiomyopathy

BackgroundSelective induction of myocardial matrix metalloproteinases (MMPs) has been reported to occur in human nonischemic dilated cardiomyopathy (DCM). We aimed to evaluate the utility of serum MMPs for risk stratification of patients with DCM.Methods and ResultsWe measured serum levels of MMP-2, MMP-3, and MMP-9 using enzyme-linked immunosorbent assay in 71 patients with mild to moderate DCM (left ventricular ejection fraction = 28.3 ± 11.5%). The primary end point was the composite incidence of cardiac death and hospitalizations for worsening heart failure. During the follow-up period (mean, 28 ± 16 months), 19 patients had major cardiac events with sudden cardiac death in 6 cases and hospitalizations for worsening heart failure in 13 cases. Multivariate analysis revealed that MMP-3 and B-type natriuretic peptide were significant independent predictors of cardiac events in patients with DCM (hazard ratio 1.41, P = .012; hazard ratio 2.72, P = .048, respectively). According to the Kaplan-Meier analyses of cumulative cardiac event-free rates of the two groups that were based on the median levels of MMPs, the differences in the cardiac event-free curves were significant only for MMP-3 (P = .009). Moreover, patients with elevations of both MMP-3 and B-type natriuretic peptide were found to have the poorest prognosis.ConclusionOur results may address the utility of serum MMP-3 for risk stratification of patients with DCM.     

CCAAT/enhancer-binding protein-d is induced in mesangial area during the early stages of anti-Thy1.1 glomerulonephritis and regulates cell proliferation and inflammatory gene expression in cultured rat mesangial cells

Background Interleukin (IL)-6, cyclooxygenase (COX)-2, and monocyte chemoattractant protein (MCP)-1 contribute to renal injury. The promoter regions of these genes contain CCAAT/enhancer-binding protein (C/EBP)-binding sites. In this study, we investigated the role of C/EBP-δ in mesangial cells (MCs). Methods In an in vivo study, anti-Thy 1.1 glomerulonephritis rats were generated and C/EBP-δ, IL-6, COX-2, and MCP-1 expressions were assessed by immunohistochemistry. In an in vitro study, cultured MCs were transfected with non-silencing (NS) short interfering RNA (siRNA) or C/EBP-δ siRNA. Subsequently, after stimulation with IL-1β, C/EBP-δ, IL-6, COX-2, and MCP-1 mRNA expression levels were evaluated using real-time polymerase chain reaction (PCR). IL-6 concentration in the culture medium was determined by enzyme-linked immunosorbent assay. In addition, cell proliferative activity against IL-1β or platelet-derived growth factor-BB was assessed by bromodeoxyuridine incorporation. Results In the in vivo study, C/EBP-δ, IL-6, COX-2, and MCP-1 were expressed in the mesangial region of anti-Thy 1.1 glomerulonephritis rats on day 1. In the in vitro study, IL-1β increased C/EBP-δ mRNA levels in NS siRNA-transfected MCs (7.3-fold), but no increase was evident in C/EBP-δ siRNA-transfected MCs. IL-6, COX-2, and MCP-1 mRNA levels in C/EBP-δ siRNA-transfected MCs were all lower than those in NS siRNA-transfected MCs (decreases of 57.7%, 85.7%, and 69.3%, respectively). The IL-6 concentration in the culture medium from C/EBP-δ siRNA transfected MCs (7.37 ± 4.3 pg/ml) was also lower than that in the culture medium from NS siRNA-transfected MCs (25.2 ± 3.4 pg/ml). Cell proliferative activity in C/EBP-δ siRNA-transfected MCs was lower than that in NS siRNA transfected MCs. Conclusions C/EBP-δ was induced in the mesangial region during the early stages of anti-Thy1.1 glomerulonephritis. C/EBP-δ contributes to inflammatory gene expression and MC proliferation.