Oxidative Stress Correlates with Left Ventricular Volume after Acute Myocardial Infarction

It has been suggested that oxidative stress may play a role in the pathophysiology of heart failure. However, little is known about the clinical relationship between oxidative stress and left ventricular dilatation after acute myocardial infarction (AMI). We prospectively studied 28 consecutive patients, successfully treated with primary coronary angioplasty, after their first AMI. To evaluate oxidative stress, plasma oxidized low-density LDL levels (U/mL) were measured serially 1 day, 7 days, 14 days, 30 days, and 90 days after the onset of AMI using a specific sandwich enzyme-linked immunosorbent assay. Left ventriculography and coronary angiography were obtained in all patients 3 months after the AMI and infarct-related arteries were all patent. Peak plasma oxidized LDL levels were seen 7 days after AMI (after 1 day: 14.71.5, 7 days: 21.02.8, 14 days: 20.22.8, 30 days: 18.32.5, 90 days: 16.52.3 U/mL). Plasma oxidized LDL levels 7 days after AMI were significantly correlated with left ventricular end-diastolic volume (1157 mL; r=0.54, P=0.0025) and end-systolic volume (585 mL; r=0.49, P=0.008) 3 months after the AMI. Moreover, they were also correlated with end-diastolic volume index (684 mL/m2, r=0.40, P<0.05). However, no correlation was seen between peak plasma oxidized LDL levels and ejection fraction. These findings suggest that oxidative stress may play an important role in the development and progression of left ventricular remodeling after AMI

Effects of ezetimibe on glucose metabolism in patients with type 2 diabetes: A 12-week, open-label, uncontrolled, pilot study

AbstractBackground: A potential effect of ezetimibe, a novel cholesterol-absorption inhibitor, on insulin resistance has been reported in an animal model.Objective: The aim of this study was to evaluate the effects of ezetimibe on glucose metabolism in patients with type 2 diabetes mellitus (T2DM).Methods: Between March and June 2008, outpatients with T2DM who were being treated at Yokohama Sakae Kyosai Hospital, Yokohama, Japan, were enrolled in this pilot study if they had not achieved the target lipid levels recommended by the Japan Atherosclerosis Society Guidelines despite diet and exercise or a statin therapy for ≥3 months. At baseline and at 4 and 12 weeks after open-label treatment with ezetimibe 10 mg/d, the levels of lipid parameters, fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), and high-sensitivity C-reactive protein were measured. Adverse effects (AEs) were assessed at each study visit by patient interviews and laboratory testing.Results: A total of 21 consecutive patients (10 men, 11 women; mean [SD] age, 72 [9] years; weight, 63.4 [10.5] kg; body mass index, 25.5 [3.2] kg/m2) were enrolled in this study. The mean (SD) level of LDL-C decreased significantly from 146 (31) to 114 (27) mg/dL (−21%; P < 0.001) after 12 weeks of treatment with ezetimibe. The mean level of remnant-like particle cholesterol also decreased significantly from 6.5 (3.8) to 4.8 (2.2) mg/dL (−15%; P = 0.03). Treatment with ezetimibe was associated with a reduction in FPG level from 127 (31) to 119 (30) mg/dL (P = 0.02), and HbAlc from 6.3% (0.6%) to 6.1% (0.7%) (P = 0.003). No AEs were observed or reported during the study period.Conclusion: In this small, open-label, uncontrolled, pilot study, ezetimibe was associated with a significant decrease in lipid parameters and improvement in glucose metabolism in these patients with T2DM

Comparison of bone marrow and adipose tissue-derived canine mesenchymal stem cells

Abstract Background Bone marrow-derived mesenchymal stem cells (BM-MSCs) and adipose tissue-derived mesenchymal stem cells (AT-MSCs) are potential cellular sources of therapeutic stem cells. MSCs are a multipotent population of cells capable of differentiating into a number of mesodermal lineages. Treatment using MSCs appears to be a helpful approach for structural restoration in regenerative medicine. Correct identification of these cells is necessary, but there is inadequate information on the MSC profile of cell surface markers and mRNA expression in dogs. In this study, we performed molecular characterization of canine BM-MSCs and AT-MSCs using immunological and mRNA expression analysis. Results Samples were confirmed to be multipotent based on their osteogenic and adipogenic differentiation. And these cells were checked as stem cell, hematopoietic and embryonic stem cell (ESC) markers by flow cytometry. BM- and AT-MSCs showed high expression of CD29 and CD44, moderate expression of CD90, and were negative for CD34, CD45, SSEA-3, SSEA-4, TRA-1-60, and TRA-1-81. SSEA-1 was expressed at very low levels in AT-MSCs. Quantitative real-time PCR (qRT-PCR) revealed expression of Oct3/4, Sox2, and Nanog in BM- and AT-MSCs. There was no significant difference in expression of Oct3/4 and Sox2 between BM-MSCs and AT-MSCs. However, Nanog expression was 2.5-fold higher in AT-MSCs than in BM-MSCs. Using immunocytochemical analysis, Oct3/4 and Sox2 proteins were observed in BM- and AT-MSCs. Conclusion Our results provide fundamental information to enable for more reproducible and reliable quality control in the identification of canine BM-MSCs and AT-MSCs by protein and mRNA expression analysis.</p

Effect of statins on the serum soluble form of receptor for advanced glycation end-products and its association with coronary atherosclerosis in patients with angina pectoris

Background: Advanced glycation end-products (AGEs) and their receptor (RAGE) play an important role in the pathogenesis of diabetic vascular complications. Recently, soluble form of RAGE (sRAGE) has been identified in mice and humans. Statins have been reported to increase serum sRAGE levels. However, whether modulation of circulating sRAGE levels has a beneficial effect on the progression of atherosclerosis is unknown. Methods: We reviewed 91 patients who had undergone percutaneous coronary intervention for angina pectoris. Coronary atherosclerosis in non-culprit lesions in the target vessel was evaluated, using virtual histology intravascular ultrasound, and serum levels of AGEs and sRAGE were measured, at baseline and after 8 months of statin therapy. Results: Statins had no effects on serum AGEs levels; however, serum levels of sRAGE were significantly higher at the 8-month follow-up. A significant decrease in external elastic membrane (EEM) volume (−1.6%, p = 0.005) was observed, whereas a decrease in plaque volume did not reach statistical significance (−1.9%, p = 0.16). Univariate regression analyses showed that the percentage changes in serum sRAGE were negatively correlated with those in EEM volume (r = −0.198, p = 0.06) and plaque volume (r = −0.247, p = 0.02). Multivariate regression analysis showed that an increase in serum sRAGE level was an independent predictor of atheroma regression after statin therapy (β = −0.290, p = 0.006). Conclusions: Statin therapy increased serum sRAGE levels, and this increase was associated with negative vessel remodeling and atheroma regression in the coronary artery