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.

Mesenchymal stem cell and bone marrow mononuclear cell therapy for cardiomyopathy: From bench to bedside.

To date, stem cell-based therapies for cardiac diseases have not achieved any significant clinical accomplishment. Globally, numerous patients are currently treated with autologous stem cells. The safety and practicality of this technique have been well-examined, its disadvantages have been recognized, and many trials have been proposed. Inadequate description of the implemented cell types, a variety of cell-handling proficiencies, and concerning factors related to autologous stem cells have been known as the central elements restricting the approval of cell-based therapies. The idea that bone marrow (BM)-derived cells could be applied to regenerate and cure damage in various organs is the basis for bone marrow mononuclear cell (BMMNC) therapy for heart disease. Mesenchymal stem cells (MSCs) are a part of the BMMNCs; on one hand, they have the capability to differentiate into various tissues, and, on the other, their immunomodulatory effects have been considered and clinically confirmed in different experiments. In this review, we summarize the knowledge obtained by trials in which mesenchymal cell-based therapy has been practiced. Furthermore, we accentuate the developments in the purification and lineage specification of MSCs as well as BMMNCs that have influenced the progress of future stem cell-based therapies with special attention on cardiovascular 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.

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.

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.

Comparative effect of grape seed extract (Vitis vinifera) and ascorbic acid in oxidative stress induced by on-pump coronary artery bypass surgery.

BACKGROUND: This study aimed to test the beneficial effect of grape seed extract (GSE) (Vitis vinifera) and Vitamin C in oxidative stress and reperfusion injury induced by cardiopulmonary bypass (CPB) in coronary artery bypass surgery. PATIENTS AND METHODS: In this randomized trial, 87 patients undergoing elective and isolated coronary bypass surgery included. The patients were randomly assigned into three groups (n = 29 each): (1) Control group with no treatment, (2) GSE group who received the extract 24 h before operation, 100 mg every 6 h, orally, (3) Vitamin C group who received 25 mg/kg Vitamin C through CPB during surgery. Blood samples were taken from coronary sinus at (T1) just before aortic cross clamp; (T2) just before starting controlled aortic root reperfusion; and (T3) 10 min after root reperfusion. Some clinical parameters and biochemical markers were compared among the groups. RESULTS: There were significant differences in tracheal intubation times, sinus rhythm return, and left ventricular function between treatment groups compared with control (P < 0.05). Total antioxidant capacity was higher (P < 0.05) in both grape seed and Vitamin C groups at T2 and T3 times. In reperfusion period, malondialdehyde level was increased in control group; however, it was significantly lower for the grape seed group (P = 0.04). The differences in the mean levels of superoxide dismutase and glutathione peroxidase among the three groups were not significant (P > 0.05 in all cases). CONCLUSIONS: In our patients, GSE and Vitamin C had antioxidative effects and reduced deleterious effects of CPB during coronary artery bypass grafting surgery.

Vasorelaxant effect of 17α-ethynylestradiol on human saphenous vein.

PURPOSE: A protective effect for estrogens against cardiovascular problems has long been known. The aim of this study was to investigate the vasorelaxant effect of 17α-Ethynylestradiol (17α-EE) on human saphenous vein. METHODS: The veins were suspended horizontally between two triangular stainless steel hooks for the measurement of isometric tension in individual organ baths containing 10ml Krebs solution, at 37°C and gassed with carbogen under 3gr optimum tension. The effect of different concentrations of 17α-EE (2-40 µM) on vascular tone was investigated in veins precontracted with PGF2α. Relaxation was measured after 40min and expressed as the percent decrease of initial contraction. To determine the involvement of potassium channels, endothelium, nitric oxide synthase, guanylylcyclase and prostaglandins in the vasorelaxant effect of estrogen, the veins were incubated with tetraethyl ammonium, N-nitro-L-arginine methyl ester, methylene blue or indomethacin, respectively for 20min prior to experimentation. Responses to 17α-EE were directly compared to those obtained in the same tissues in the absence of the inhibitors. RESULTS: The mean relaxations induced by 17α-EE with concentrations of 2, 5, 10, 20 and 40µM in tissues precontracted with PGF2α were 19.8 ±5.5%, 26.1±10.8%, 32.2±7.4%, 48.6±10.8%and56±7.6%, respectively. The results of the inhibition of potassium channels, nitric oxide synthase, guanylylcyclase, cyclooxygenase and removing endothelium in relaxation induced by 17α-EE on precontracted veins with PGF2α proved no significant differences. CONCLUSION: This study showed that 17α-EE has significant vasorelaxant effect on human saphenous vein in a concentration-dependent manner. This effect is probably independent of potassium channels, nitric oxide synthase, guanylylcyclase, prostaglandin synthesis and endothelium functions.

Depression in coronary artery disease.

INTRODUCTION: Depression is one of the Common psychological disorders. From the cognitive point of view, the unhealthy attitudes increase the severity of the depression. The aim of this study was to investigate depression and unhealthy attitudes in coronary patients hospitalized at Tabriz Shahid Madani Heart Center. METHODS: One hundred twenty eight hospitalized patients having myocardial Infarctions were studied regarding unhealthy attitudes, severity of depression and demographic data. RESULTS: The study showed a significant relation between unhealthy attitudes, BDI (Beck Depression Inventory) and severe depression. Moreover, a significant relation existed between gender and depression (P=0.0001). In addition, the level of education increased the intensity of unhealthy attitudes (P=0.0001). Several researches in both outside and inside Iran support the idea. CONCLUSION: Based on present study and more other investigations, it can be suggested to provide the necessary elements and parameters such as antidepressant medication, psychologists, complementary treatment for coping with negative mood and its unwanted consequences.

New procedure for treatment of atrial fibrillation in patients with valvular heart disease.

Patients with valvular heart disease suffer from atrial fibrillation for more than 12 months after valve surgery and have a low probability of remaining in sinus rhythm. We performed an intra-operative procedure similar to surgical maze ІІІ procedure for conversion of this arrhythmia to sinus rhythm. We did this study to evaluate the efficacy of this procedure to restore the sinus rhythm in patients with valvular heart disease. 28 patients with valvular heart disease and chronic persistent atrial fibrillation underwent different combinations of valve surgery and concomitant reduction of left and right atrial size and resection of both atrial auricles in Shahid Madani cardiothoracic center from September 2004 to October 2008. The procedure for atrial fibrillation treatment was performed with cardiopulmonary bypass and after mitral valve replacement. There was one in-hospital death postoperatively because of respiratory failure, but no other complication till 6 months after the operation. Out of 28 patients, 23 were in sinus rhythm one week after the operation, one patient had junctional rhythm after the operation that restored to sinus rhythm and 4 patients had persistent atrial fibrillation. During the 12-month follow up, atrial fibrillation was corrected in 82.14%. Doppler echocardiography in these patients with sinus rhythm demonstrated good atrial contractility. This procedure on both atria is effective and less invasive than the original maze procedure to eliminate the atrial fibrillation, and can be performed in patients with valvular heart disease without increasing the risk of operation.