Dapagliflozin attenuates high glucose-induced endothelial cell apoptosis and inflammation through AMPK/SIRT1 activation.

Hyperglycaemia is a major cause of pathophysiological processes such as oxidative stress, inflammation, and apoptosis in diabetes. Dapagliflozin (DAPA), a novel hypoglycaemic drug, has been shown to have anti-apoptotic, anti-inflammatory, and antioxidant effects in multiple experimental studies. In this study, we investigated the protective effects of DAPA in the hyperglycaemic condition to identify associated molecular mechanisms. human umbilical vein endothelial cells (HUVEC) endothelial cells were treated with 40 mM glucose for 72 h to establish an in vitro high glucose (HG) condition model, and then additional groups co-treated with or without DAPA before glucose treatment. Then, cell viability, reactive oxygen species (ROS), pro-inflammatory cytokines (IL-6 and TNF-α), apoptosis, and SIRT1 expression were measured. The results showed that DAPA pretreatment resulted in increased cell viability. Additionally, DAPA pretreatment decreased endothelial ROS, IL-6, and TNF-α levels in endothelial cells subjected to HG conditions. Moreover, DAPA pretreatment significantly prevented HG-induced apoptosis and caspase-3 activity in HUVECs. Furthermore, DAPA increased the expression of SIRT1, PGC-1α, and increased the phosphorylation levels of AMPK (p-AMPK) in a set of HG conditions in HUVECs. However, the endothelial protective effects of DAPA were abolished when cells were subjected to the SIRT1 inhibitor (EX-527) and AMPK inhibitor (Compound C). These findings suggest that DAPA can abrogate HG-induced endothelial cell dysfunction by AMPK/SIRT1 pathway up-regulation. Therefore, suggesting that the activation of AMPK/SIRT1 axis by DAPA may be a novel target for the treatment of HG-induced endothelial cell injury.

The serum levels of testosterone in coronary artery disease patients; relation to NO, eNOS, endothelin-1, and disease severity.

OBJECTIVES: The changes in testosterone level and its correlation with the endothelial nitric oxide systems balance in patients with coronary artery disease (CAD) remains uncertain. Therefore, in our study, we aimed to evaluate the levels of testosterone, endothelin-1 (ET-1), nitric oxide (NO), and endothelial NOS (eNOS) in CAD patients, and control group to find the relationship between these parameters and disease severity. METHODS: Forty-four patients as CAD group with significant (≥50%) stenosis confirmed by angiography was included in the study, and 40 healthy men were included as the control group. According to the number of vessels obstruction, CAD severity was determined. The serum indicated parameters were assessed to discriminate between patients and controls. RESULTS: It was found that testosterone levels in the CDA group were significantly lower than those of the control group (p<0.05). In addition, the level of ET-1 in the CAD group was higher than that in the control group, but levels of NO and eNOS in observation were significantly lower than those in the control group (p<0.05). The correlation analysis revealed that testosterone was passivity correlated with serum NO levels (r=0.550, p=0.001). CONCLUSIONS: The current study reports that serum levels of testosterone are closely related to endothelial NO levels and might be of relevance to the pathogenesis of endothelial dysfunction and disease severity in CAD patients.

Amnion membrane proteins attenuate LPS-induced inflammation and apoptosis by inhibiting TLR4/NF-κB pathway and repressing MicroRNA-155 in rat H9c2 cells.

OBJECTIVE: Amnion membrane (AM) has been popular for the treatment of inflammatory disorders due to its cell repairing properties. This current study aims to find the underlying mechanisms of amnion membrane proteins (AMPs) against the pro-inflammatory miRNA, miR-155, miR-146, and anti-apoptotic microRNA, miR-21, in LPS-treated H9c2 cells. METHODS: Cell viability and apoptosis were determined by MTT assay and annexin V/PI staining. The production of the cytokines, TNF-α and IL-6 were evaluated by using qPCR and Enzyme-linked immunosorbent assay (ELISA), respectively. In addition, the expression of miRNAs was quantified by qPCR, and also the protein level of TLR4 and NF-kß was determined with western blotting. RESULTS: We found that AMPs ameliorated LPS-induced reduction of cell viability and augment apoptosis in H9c2 cells. AMPs efficiently inhibited cytokine expression (IL-6 and TNF-α) and activity of TLR4/NF-κB pathway in LPS-treated H9c2 cells. Correspondingly, in parallel with the suppression of pro-inflammatory cytokines and apoptosis, AMPs mitigated pro-inflammatory miRNA, miR-155 expression, while, the expression of miR-155 was found to be increased in LPS-treated H9c2 cells. Also, AMPs activated miR-146 expression in H9c2 cells under LPS treatment. Additionally, the elevated expression of miR-21 provoked by LPS was further enhanced by AMPs. CONCLUSIONS: In conclusion, AMPs could alleviate LPS-induced cardiomyocytes cells injury via up-regulation of miR-21, miR-146, and suppression of TLR4/NF-κB pathway, which plays a key role in the down-regulation of LPS-mediated miR-155 and inflammatory cytokine expression.

Human Amnion Membrane Proteins Prevent Doxorubicin-Induced Oxidative Stress Injury and Apoptosis in Rat H9c2 Cardiomyocytes.

Doxorubicin (DOX) is widely used as an effective chemotherapy agent in cancer treatment. Cardiac toxicity in cancer treatment with DOX demand urgent attention and no effective treatment has been established for DOX-induced cardiomyopathy. It has been well documented that human amniotic membrane proteins (AMPs), extracted from amnion membrane (AM), have antioxidant, anti-apoptotic, and cytoprotective properties. Therefore, in this study, we aimed to investigate the protective effects of AMPs against cardiotoxicity induced by DOX in cultured rat cardiomyocyte cells (H9c2). DOX-induced cell injury was evaluated using multi-parametric assay including thiazolyl blue tetrazolium bromide (MTT), the release of lactic dehydrogenase (LDH), intracellular Ca2+ , reactive oxygen species (ROS) levels, cellular antioxidant status, mitochondrial membrane potential (ΔΨm), malondialdehyde (MDA), and NF-κB p65 DNA-binding activity. Moreover, expression profiling of apoptosis-related genes (P53, Bcl-2, and Bax) and Annexin V by flow cytometry were used for cell apoptosis detection. It was shown that AMPs pretreatment inhibited the cell toxicity induced by DOX. AMPs effectively attenuated the increased levels of LDH, Ca2+ , ROS, and MDA and also simultaneously elevated the ΔΨm and antioxidant status such as superoxide dismutase (SOD) and Catalase (CAT) in pretreated H9c2 cardiomyocytes. Besides, the activity of NF-kB p65 was reduced and the p53 and Bax protein levels were inhibited in these myocardial cells subjected to DOX. These findings provide the first evidence that AMPs potently suppressed DOX-induced toxicity in cardiomyocytes through inhibition of oxidative stress and apoptosis. Thus, AMPs can be a potential therapeutic agent against DOX cardiotoxicity.

Different expression of Micro RNA-126, 133a and 145 in aorta and saphenous vein samples of patients undergoing coronary artery bypass graft surgery.

Introduction: microRNAs (miRNAs) are highly conserved, noncoding RNA molecules that regulate gene expression on the post-transcriptional level. Some evidence indicates that microRNAs dysfunction plays a crucial role in human disease development. The role of microRNAs in cardiac growth, hypertrophy, heart failure, cardiovascular complications in diabetes and many other hearth conditions are demonstrated. In this study we aimed to evaluate the expression of six microRNAs (mir-100, mir-126, mir-127, mir-133a, mir-133b and mir-145) that have been shown to overexpress in aortic and carotid plaques. Methods: Thirty Coronary Artery Disease patients who underwent elective coronary artery bypass graft surgery were enrolled in the study. The expression patterns of six miRNAs (mir-100, mir-126, mir-127, mir-133a, mir-133b, and mir-145) were examined in 30 patients of whom we obtained aorta and saphenous vein samples. Results: In three miRNAs, mir-100, mir-127 and mir-133b, we did not obtain expression data from real-time experiments. We found that the expression level of mir-126, mir-133a and mir145 were lower in aorta in comparison with saphenous vein. Mir-126 was highly expressed in saphenous vein samples (13.8±1.1) when compared with aorta samples (20.2±1.1), although mir133a was highly expressed in saphenous vein samples (16.1±0.5) when compared with the aorta (17.9±1.5). Expression of mir-145 saphenous vein samples was also dramatically higher than aorta (7.2±0.5 versus 10.8±0.6) that was statistically significant (P<0.05). Conclusion: Understanding the role of miRNAs in cardiovascular physiology and diseases might suggest miRNA- based therapeutic methods in the management of coronary artery disease.

Stem cells as therapy for heart disease: iPSCs, ESCs, CSCs, and skeletal myoblasts.

Heart Diseases are serious and global public health concern. In spite of remarkable therapeutic developments, the prediction of patients with Heart Failure (HF) is weak, and present therapeutic attitudes do not report the fundamental problem of the cardiac tissue loss. Innovative therapies are required to reduce mortality and limit or abolish the necessity for cardiac transplantation. Stem cell-based therapies applied to the treatment of heart disease is according to the understanding that natural self-renewing procedures are inherent to the myocardium, nonetheless may not be adequate to recover the infarcted heart muscle. Following the first account of cell therapy in heart diseases, examination has kept up to rapidity; besides, several animals and human clinical trials have been conducted to preserve the capacity of numerous stem cell population in advance cardiac function and decrease infarct size. The purpose of this study was to censoriously evaluate the works performed regarding the usage of four major subgroups of stem cells, including induced Pluripotent Stem Cells (iPSC), Embryonic Stem Cells (ESCs), Cardiac Stem Cells (CDC), and Skeletal Myoblasts, in heart diseases, at the preclinical and clinical studies. Moreover, it is aimed to argue the existing disagreements, unsolved problems, and prospect directions.

Nrf2 activation and down-regulation of HMGB1 and MyD88 expression by amnion membrane extracts in response to the hypoxia-induced injury in cardiac H9c2 cells.

BACKGROUND: human Amniotic Membrane (hAM) extracts contain bioactive molecules such as growth factors and cytokines. Studies have confirmed the ability of hAM in reduction of post-operative dysfunction in patients with cardiac surgery. However, the function of Amniotic Membrane Proteins (AMPs), extracted from hAM, against hypoxia-induced H9c2 cells injury have never been investigated. In this study, we aimed to appraise the protective impact of AMPs on H9c2 cells under hypoxia condition. METHODS: Cardiomyocyte cells were pre-incubated with AMPs and subjected to 24 h hypoxia to elucidate its effects on expression of Nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1(HO-1). Furthermore, the high mobility group box-1 (HMGB1) and Myeloid differentiation primary response 88 (MyD88) expressions were detected by qPCR and western-blotting. The mitochondrial membrane potential (ΔΨm) was estimated by JC-1 using fluorescent microscopy and fluorimetry. Moreover, the cell apoptosis and intracellular calcium levels were measured by flow cytometry. RESULTS: Pre-treatment of AMPs resulted in significant induction in cell viability and decreased the LDH release under hypoxic condition in H9c2 cells. Accordingly, these protective effects of AMPs were associated with a reduction in apoptosis rates and intracellular Ca2+, meanwhile, ΔΨm was increased. Pre-treatment with AMPs resulted in degradation of HMGB1 and MyD88 levels and depicted pro-survival efficacy of AMPs against hypoxia-induced cell damage through induction of HO-1 and Nrf2. CONCLUSION: The data indicated that AMPs mediated HO-1 regulation by Nrf2 activation and plays critical protective effects in hypoxia-induced H9c2 injury in vitro by the inhibition of myocardial HMGB1 and MyD88 inflammatory cascade.

The role of sphingosine 1 phosphate in coronary artery disease and ischemia reperfusion injury.

Coronary artery disease (CAD) is a common cause of morbidity and mortality worldwide. Atherosclerotic plaques, as a hallmark of CAD, cause chronic narrowing of coronary arteries over time and could also result in acute myocardial infarction (AMI). The standard treatments for ameliorating AMI are reperfusion strategies, which paradoxically result in ischemic reperfusion (I/R) injury. Sphingosine 1 phosphate (S1P), as a potent lysophospholipid, plays an important role in various organs, including immune and cardiovascular systems. In addition, high-density lipoprotein, as a negative predictor of atherosclerosis and CAD, is a major carrier of S1P in blood circulation. S1P mediates its effects through binding to specific G protein-coupled receptors, and its signaling contributes to a variety of responses, including cardiac inflammation, dysfunction, and I/R injury protection. In this review, we will focus on the role of S1P in CAD and I/R injury as a potential therapeutic target.

Distinct role of autophagy on angiogenesis: highlights on the effect of autophagy in endothelial lineage and progenitor cells.

Autophagy plays a critical role in the dynamic growth of each cell through different conditions. It seems that this intracellular mechanism acts as a two-edged sword against the numerous cell insults. Previously, autophagy was described in the context of cell activity and behavior, but little knowledge exists related to the role of autophagy in endothelial cells, progenitors, and stem cells biology from different tissues. Angiogenic behavior of endothelial lineage and various stem cells are touted as an inevitable feature in the restoration of different damaged tissues and organs. This capacity was found to be dictated by autophagy signaling pathway. This review article highlights the fundamental role of cell autophagic response in endothelial cells function, stem cells dynamic, and differentiation rate. It seems that elucidation of the mechanisms related to pro- and/or anti-angiogenic potential of autophagy inside endothelial cells and stem cells could help us to modulate stem cell therapeutic feature post-transplantation.

SIRT3-mediated cardiac remodeling/repair following myocardial infarction.

The recent investigations have extensively focused on the importance of sirtuins, as a highly conserved family of gene products, particularly SIRT3 in various biological and pathological processes. SIRT3, the mitochondrial NAD+-dependent deacetylase has been demonstrated to target a broad range of proteins involved in the oxidative stress, ischemia-reperfusion injury, mitochondrial metabolism homeostasis and cellular death. The critical function of SIRT3 in myocardial infarction (MI), which is one of the complex phenotype of coronary artery disease and a result of interaction between various genetic and environmental factors, as well as in cardiac repair and remodeling post-MI have attracted more attention in the recent years. Therefore, in this review, we will summarize important literature about the involvement of SIRT3 in cardiac remodeling/repair following MI and its potential underlying mechanisms.

N1-methylnicotinamide (MNAM) as a guardian of cardiovascular system.

Atherosclerosis is identified as the formation of atherosclerotic plaques, which could initiate the formation of a blood clot in which its growth to coronary artery can lead to a heart attack. N-methyltransferase (NNMT) is an enzyme that converts the NAM (nicotinamide) to its methylated form, N1-methylnicotinamide (MNAM). Higher levels of MNAM have been reported in cases with coronary artery disease (CAD). Further, MNAM increases endothelial prostacyclin (PGI2) and nitric oxide (NO) and thereby causes vasorelaxation. The vasoprotective, anti-inflammatory and anti-thrombotic roles of MNAM have been well documented; however, the exact underlying mechanisms remain to be clarified. Due to potential role of MNAM in the formation of lipid droplets (LDs), it might exert its function in coordination with lipids, and their targets. In this study, we summarized the roles of MNAM in cardiovascular system and highlighted its possible mode of actions.

The role of cholesterol-enriched diet and paraoxonase 1 inhibition in atherosclerosis progression.

Introduction: Atherosclerosis could be deemed as a chronic, progressive, and inflammatory disease. It has been well-documented that high-density lipoprotein (HDL) can reduce the risk of the atherosclerosis occurrence through exerting some anti-atherogenic mechanisms. In recent years, the strong evidence has suggested that paraoxonase 1 (PON1) may contribute to antioxidant properties of HDL. In the present study, the impact of a diet enriched with cholesterol and also the PON1 inhibition on atheroma formation and lipid profile has been investigated. Methods: In this study, 24 New Zealand rabbits were randomly assigned to three groups receiving standard diet, atherogenic diet, and atherogenic diet plus once daily intramuscular injection of nandrolone decanoate as the PON1 inhibitor. Triglyceride, cholesterol, HDL, and low-density lipoprotein (LDL) were determined and both cholesterol accumulation in aorta and fatty streak formation were evaluated. Results: The comparison of the results in three groups reveals that cholesterol level in the group received cholesterol-enriched diet plus once daily injection of PON1 inhibitor was higher than the groups received standard diet or atherogenic diet without PON1 inhibitor (P < 0.05). Furthermore, the percentage of atheroma with type-I lesions was equal to 75% compared with the group received atherogenic diet plus nandrolone at 30%. Additionally, the differences in fatty streak formation in aorta, as well as the right and left coronary arteries in three groups given show that the difference between groups receiving atherogenic diet and standard diet was significantly lower (P < 0.05) than the difference between groups receiving atherogenic diet plus PON1 inhibitor and standard diet. Conclusion: It can be concluded that lack of paraoxanase1 or even reduced the activity of this enzyme could accelerate the progression of fatty streak lesions toward advanced atherosclerotic lesions.

Fatty acids composition of aorta and saphenous vein tissues in patients with coronary artery diseases.

Introduction: Considering importance of fatty acids in developing coronary artery disease (CAD) and lack of information about saphenous vein which is commonly used as coronary arterial bypass, in this study we investigated differences in fatty acids composition between saphenous vein and aorta tissues in patients with CAD. Methods: Biopsy samples of aortic tissues and saphenous veins as well as blood samples were obtained form 42 patients with CAD. Fatty acids composition of the tissues was determined using gas chromatography and also serum lipid profile was evaluated by commercial kits. Results: Levels of palmitic acid (16:0) were significantly higher in aorta in compared with saphenous (P < 0.001). Also levels of most unsaturated fatty acids (16:1, 18:1n-9, 18:1t, 18:2t, 18:3 n-9 and 22:3n-3) were statistically higher in saphenous tissue than aorta tissue (P < 0.05). Mean levels of linoleic acid (18:2 n-6) was higher in aorta tissue in comparison with saphenous tissue (P = 0.01). We observed positive correlations between serum levels of LDL-C with elaidic acid and linoleic acid levels in saphenous. Evaluation of aorta tissue fatty acids revealed that palmitoleic acid (16:1) had positive and arachidonic and linoleic acids had negative correlations with serum HDL-C levels. Conclusion: Our results revealed difference between fatty acids composition of aorta and saphenous vein tissues and existence of correlations between the fatty acids levels with serum lipid profile. The saphenous vein had higher poly-unsaturated fatty acids in compared to aorta tissue and thus this vein is not at risk of atherosclerosis and can be used as coronary arterial bypass.

Bovine lactoferrin ameliorates antioxidant esterase activity and 8-isoprostane levels in high-cholesterol-diet fed rats.

The main aim of the present study was to show the effect of bovineLactoferrin (bLF), an 80 kD iron-binding glycoprotein, its application on antioxidant esterase activities and 8-isoprostane changes in high-cholesterol-diet fed (HCD-Fed) rats. The 44 adult Sprague-Dawley male rats were randomly assigned into four experimental groups. They were randomly assigned into four equivalent groups (n = 11). The groups included the control group which was fed with normal diet, bLF group, the third group which were made hypercholesterolemia by being fed with high cholesterol diet, and the last group which consisted of hypercholesterolemia rats treated with bLF (HCD + bLF) for 4 weeks (200 mg.kg-1 per day wt. dissolved in 0.9% normal saline).After 4 weeks, the serum Paraoxonase1 (PON1), Arylesterase (ARE) activity and 8-isoprostane with lipid profile were measured. Upon treatment with the bLF, the decrease in LDL-Cholesterol (LDL-C), Glucoses, Triglyceride (TG) and Total-Cholesterol (TC) levels and an increase in HDL-Cholesterol (HDL-C) level were observed. The co-administration of bLf for 4 weeks had decreased the 8-isoprostane levels significantly (P < 0.001) (86.36 ± 7.1 vs 117.18 ± 8.62) when compared to hypercholesterolemia-induced rats. Also, the Atherogenic Index (AI) in HCD + bLF group showed a significant decrease as compared to the HCD group (P < 0.001) (0.37 ± 0.07 vs 0.57 ± 0.09). The results indicated that bLF was effective against oxidative stress by its ability to increase PON1 activity and reduce the lipid peroxidation in high-cholesterol-fed rats.

Hydrocortisone reduces Toll-like receptor 4 expression on peripheral CD14+ monocytes in patients undergoing percutaneous coronary intervention.

BACKGROUND: Evidence from several lines of investigations suggests that Toll-like receptor 4 (TLR4) is involved in atherosclerosis as a bridge between innate and acquired immunity. Percutaneous coronary intervention (PCI) can trigger inflammation through activation of human TLR4 (hTLR4) on monocytes. Hydrocortisone as an anti-inflammatory and immuno-suppressant agent has multiple mechanisms of action. In this study, we aimed at assessing the effects of hydrocortisone on monocyte expression and activity of hTLR4 in patients underwent PCI. METHODS: Blood samples were taken from a total of 71 patients with chronic stable angina who were scheduled for a PCI, before the intervention. Thirty patients received 100 mg hydrocortisone prior to the procedure. Control group was composed of 41 patients underwent PCI without receiving hydrocortisone. Blood collection was repeated 2 and 4 h after PCI. The expression of hTLR4 on the surface of CD14+ monocytes and the serum levels of TNF-α and IL-1ß were measured using flowcytometry and Sandwich ELISA. RESULTS: Compared with controls, hydrocortisone significantly reduced monocyte expression of hTLR4 in test group (P<0.01). In addition, it had a significant effect on reduction of serum concentrations of TNF-α and IL-1ß in test group in a time-dependent manner (P<0.01). CONCLUSION: In this study, hydrocortisone was able to reduce the hTLR4/CD14 positive monocytes and its related pro-inflammatory cytokines, thus it can decrease inflammatory responses following PCI.

The Role of Esophagogastric Anastomotic Technique in DecreasingBenign Stricture Formation in the Surgery of Esophageal Carcinoma.

INTRODUCTION: Postoperative stenosis and dysphagia after esophageal carcinoma resection is the major problem. The aim of this study is to compare two types cervical esophagogastric anastomosis in reduction of stricture formation in esophageal cancer surgery. METHODS: The subjects of this study were 223 patients undergoing esophageal carcinoma resection during 1998 to 2007. Twenty two patients were excluded from the study because of recurrent malignancy of anastomosis, mortality and losing in follow up period. Two hundred and one patients remained by the end of study were classified into two groups: 98 patients were treated by routinely transverse hand-sewn cervical esophagogastric anastomosis (group 1); and 103 patients were treated by the proposed oblique hand-sewn esophagogastric anastomotic technique (group 2). All the operations were with high abdominal and left cervical incisions (Transhiatal esophagectomy). All patients of both groups were followed up at least 6-month for detection of anastomotic strictures. RESULTS: Postoperative dysphagia occurred in 20 patients of group 1 versus 5 patients of group 2. In working up by rigid esophagoscopy, two patients of group 2 and four patients of group 1 had not true strictures. Anastomotic strictures occurred in 16 cases of group 1, versus 3 cases of group 2. Statistical comparative analysis results of two groups about stricture formation were significant (3% versus 16% P= 0.003). CONCLUSION: The oblique hand-sewn esophagogastric anastomostic techniques reduce markedly the rate of stricture formation after esophagectomy.

Evaluation of Early and Intermediate Outcomes of Cryo-MazeProcedure for Atrial Fibrillation.

INTRODUCTION: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in patients with mitral valve disease affecting 50% of patients undergoing mitral valve surgery, contributing to increased risks of systemic embolization, anticoagulant- related hemorrhage and mortality. The maze procedure is an effective way to treat AF. Over the last several years, cryoablation was substituted for atrial incision in many reports to simplify the maze procedure. However, few studies have been carried out to evaluate the results of cryoablation surgery. In the present study we evaluated the results of this procedure. METHODS: In this cross sectional study, 47 AF patients were treated with Cryo-Maze surgery method. Rhythm assessment using electrocardiographic and echocardiographic survey was performed in all patients before surgery, during the patients' hospital stay, on discharge and after six months. RESULTS: Survival rate of the studied patients at six months was 93.6%. Sinus rhythm restoration rate in Cryo-Maze patients was 72.1% on discharge and 76.7% six months after their operation. CONCLUSION: The present study revealed that Cryo-Maze procedure is an effective and safe therapeutic modality in AF while normal sinus rhythm can be achieved in patients following this intervention.

Protective effects of methylsulfonylmethane on hemodynamics and oxidative stress in monocrotaline-induced pulmonary hypertensive rats.

Methylsulfonylmethane (MSM) is naturally occurring organic sulfur that is known as a potent antioxidant/anti-inflammatory compound. The aim of this study was to investigate the effect of MSM on hemodynamics functions and oxidative stress in rats with monocrotaline- (MCT-) induced pulmonary arterial hypertension (PAH). Wistar rats were randomly assigned to 38-days treatment. MSM was administered to rats at 100, 200, and 400 mg/kg/day doses 10 days before a single dose of 60 mg/kg, IP, MCT. Hemodynamics of ventricles were determined by Powerlab AD instrument. Blood samples were obtained to evaluate changes in the antioxidative system including activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and the level of reduced glutathione (GSH) and malondialdehyde (MDA). Improvements in cardiopulmonary hemodynamics were observed in the MSM-treated pulmonary arterial hypertensive rats, with a significant reduction in right ventricular systolic pressure (RSVP) and an increase in the mean arterial pressure (MAP). The values of CAT, SOD, GSH-px activities, and GSH were significantly lower in MCT-induced PAH (P < 0.01), but they were recovered to control levels of MSM-treated groups. Our present results suggest that long-term administration of the MSM attenuates MCT-induced PAH in rats through modulation of oxidative stress and antioxidant defense.

Fatty acid composition of epicardial and subcutaneous human adipose tissue.

BACKGROUND: Epicardial adipose tissue has special properties that distinguish it from the more widely studied depots of adipose tissue. OBJECTIVES: We undertook this study to investigate regional differences between epicardial and subcutaneous adipose tissue fat composition, as well as associations between these measures and metabolic variables. METHODS: Epicardial and subcutaneous peripheral adipose tissue were collected during coronary artery bypass grafting from 42 patients (ages 37-65) with coronary artery disease (CAD). The fatty acid composition of adipose tissue was determined by gas liquid chromatography (GLC). RESULTS: The saturated fatty acids, including myristic acid (14:0), palmitic acid (16:0), and stearic acid (18:0), were higher, and the unsaturated fatty acids, including palmitoleic acid (16:1n-7), oleic acid (18:1n-9), linoleic acid (18:2n-6), and linolenic acid (18:3n-3), were lower than the subcutaneous adipose tissue. The presence of hypertension was positively correlated with the 16:1n-7 (r = 0.407, P = 0.032) and 18:1n-11(r = 0.370, P = 0.027), and negatively correlated with 18:1n-9 (r = -0.367, P = 0.036) and 18:2n-6 (r = -0.446, P = 0.006) contents of epicardial adipose tissue after adjustment for body mass index. CONCLUSIONS: Regional differences may be observed in fatty acid composition, suggesting a depot specific impact of stored fatty acids on adipocyte function and metabolism.