Galectin-1 in early acute myocardial infarction

Myocardial infarction (MI) is the most serious manifestation of coronary artery disease and the cause of significant mortality and morbidity worldwide. Galectin-1(GAL-1), a divalent 14.5-kDa protein, is present both inside and outside cells, and has both intracellular and extracellular functions. Hypoxia inducible factor-1 alpha (HIF-1α) is a transcription factor mediating early and late responses to myocardial ischemia. Identification of the pattern of expression of GAL-1 and HIF-1α in the heart during the first 24 hours following acute MI will help in understanding early molecular changes in this event and may provide methods to overcome serious complications. Mouse model of MI was used and heart samples were processed for immunohistochemical and immunofluorescent labeling and Enzyme linked immunosorbent assay to identify GAL-1 and HIF 1α levels in the heart during the first 24 hours following MI. There was significant increase in left ventricular GAL-1 at 20 (p = 0.001) and 30 minutes (p = 0.004) following MI. There was also a significant increase in plasma GAL-1 at 4 hours (p = 0.012) and 24 hours (p = 0.001) following MI. A significant increase in left ventricular HIF-1 α was seen at 20 minutes (p = 0.047) following MI. In conclusion, we show for the first time that GAL-1 level in the left ventricle is increased in early ischemic period. We also report for the first time that HIF-1 α is significantly increased at 20 minutes following MI. In addition we report for the first time that mouse plasma GAL-1 level is significantly raised as early as 4 hours following MI

Myocardial ischemia reperfusion injury: Apoptotic, inflammatory and oxidative stress role of galectin-3

Background/aims: Myocardial reperfusion has the potential to salvage the ischemic myocardium after a period of coronary occlusion. Reperfusion, however, can cause a wide spectrum of deleterious effects. Galectin-3 (GAL-3), a beta galactoside binding lectin, is closely associated with myocardial infarction (MI), myocardial fibrosis and heart failure. In our study, we investigated its role in ischemia-reperfusion injuries (IR) as this phenomenon is extremely relevant to the early intervention after acute MI.Methods: C57B6/J wild type (WT) mice and GAL-3 knockout (KO) mice were used for murine model of IR injury in the heart where a period of 30 minutes ischemia was followed by 24 hours of reperfusion. Heart samples were processed for immunohistochemical and immunofluorescent labeling, morphometric analysis, western blot and enzyme-linked immunosorbent assay to identify the apoptotic, inflammatory and oxidative stress role of GAL-3.Results: Our results show that there was a significant increase in GAL-3 levels in the heart which shows GAL-3 is playing a role in the ischemia reperfusion injury. Troponin I was also significantly higher in GAL-3-KO group than wild type. Our study shows that GAL-3 is associated with an increase in the antioxidant activity in the IR injured myocardium. Antioxidant enzymes superoxide dismutase, glutathione and catalase were found to be significantly raised in the GAL-3 wild type IR as compared to the GAL-3 KO IR group. A significant increase in apoptotic activity is seen in GAL-3 KO IR group as compared with GAL-3 wild IR group.Conclusion: Our study shows that GAL-3 can affect the redox pathways, controlling cell survival and death, and plays a protective role on the myocardium following IR injury

Acute myocardial infarction and myocardial ischemia-reperfusion injury: A comparison

Myocardial infarction (MI) denotes the death of cardiac myocytes due to extended ischemia. Myocardial reperfusion is the restoration of coronary blood flow after a period of coronary occlusion. Reperfusion has the potential to salvage ischemic myocardium but paradoxically can cause injury, a phenomenon called as \u27reperfusion injury\u27 (IR). Standard histologic, immunohistochemical and Elisa techniques were used to study the histopathologic, oxidative, apoptotic and inflammatory changes in MI and IR. The IL-6 levels in the LV of the MI group were significantly raised as compared to the IR group (P=0.0008). Plasma IL-6 was also significantly increased in the MI group as compared to the IR group (P=0.031). MI model was also associated with increase in the neutrophil polymorphs number in the infarction related myocardium as compared to the re-perfused myocardium. A significant increase in troponin I level in the MI group as compared to the IR group is also seen (P=0.0001). Our IR model showed enhanced pro-apoptotic mediators like cleaved caspase-3 (P=0.005) and cytochrome c in the myocardium as compared to the MI model. In conclusion, myocardial damage in MI is mainly due to ischemic necrosis and inflammatory mechanisms while apoptosis is the main mechanism of cell death in IR in addition to limited ischemic necrosis

Galectin-1: A biomarker of surgical stress in murine model of cardiac surgery

Galectin-1 (GAL-1) belongs to the family of β-galactoside-binding lectins. It regulates cell-cell and cell-matrix interactions, the immune response, apoptosis, cell cycle, RNA splicing and neoplastic transformation. We investigate the effect of heart manipulation secondary to cardiac surgery on the level of GAL-1 in murine heart and plasma. Male C57B6/J mice were used for adopted model of cardiac surgery. Heart samples were processed for immunohistochemical and immunofluorescent labeling, Enzyme linked immunosorbent assay and quantitative RT-PCR to identify GAL-1 levels in the heart and plasma during the first 24 hours following cardiac surgery. There is significant increase of GAL-1 in the LV at 30 minutes (

Loss of dystrophin staining in cardiomyocytes: A novel method for detection early myocardial infarction

Myocardial infarction (MI) is the most frequent diagnosis made in majority of sudden death cases subjected to clinical and medicolegal autopsies. When sudden death occurs at a very early stage of MI, traditional macroscopic examination, or histological stains cannot easily detect the myocardial changes. For this reason we propose a new method for detecting MI at an early stage. Murine model of MI was used to induce MI through permanent ligation of left anterior descending branch of left coronary artery. Five groups of C57B6/J mice were used for inducing MI, which includes 20 minutes, 30 minutes, one hour, four hours and 24 hours post MI groups. One naïve group and sham-operated groups were used as controls. There is loss of dystrophin membranous staining in cardiac myocytes occurs as early as 20 minutes post myocardial infarction. This can be used as a novel method to diagnose early myocardial infarction in post mortem cases where diagnosis is unclear. In conclusion, evaluation of immunohistochemical expression of dystrophin represents a highly sensitive method for detecting early myocardial infarction due to the loss of staining in the infarcted areas. Dystrophin immunostaining can also be used to assess myocardial architecture

Galectin-3: A cardiomyocyte antiapoptotic mediator at 24-hour post myocardial infarction

Background/Aims: Galectin 3 (GAL-3) is a beta galactoside binding lectin that has different roles in normal and pathophysiological conditions. GAL-3 has been associated with heart failure and was linked to increased risk of death in a number of studies. GAL-3 was found to be up regulated in animal models of heart failure as well as myocardial infarction (MI). The objective of his study is to test if high GAL-3 after myocardial infarction has a protective role on the heart through its anti-apoptotic and anti-necrotic functions.Methods: Male C57B6/J mice and GAL-3 knockout (KO) mice were used for permanent ligation of the left anterior descending artery of the heart to create infarction in the anterior myocardium. Heart and plasma samples were collected 24 hours after the induction of MI and were used for immunohistochemistry, Tunnel procedure, electron microscopy and enzyme linked immunosorbent assay (ELISA).Results: Our results show that the significant increase in GAL-3 levels in the left ventricle at 24-hour following MI is associated with significant lower levels of pro-apoptotic proteins; cytochrome c, Bax, annexin V, cleaved caspase-3 and a higher levels of anti-apoptotic protein Bcl2 in GAL-3 wild MI group than GAL-3 KO group. We also have identified the anti-apoptotic activity of GAL-3 is mediated through a significant increase in Akt-1, NF kappa-B and beta- catenin proteins. In addition, we have identified the antiapoptotic activity is mediated through a significant lower levels of cathepsin-D protein.Conclusion: We conclude that the increased levels of GAL-3 at 24-hour following MI regulate antiapoptotic mechanisms in the myocardium that will shape the future course of the disease. We also identified that the anti-apoptotic mechanisms are likely mediated through interaction of GAL-3 with Akt-1, NF kappa-B, beta- catenin and cathepsin D proteins

Impact of prolonged exposure to occasional and regular waterpipe smoke on cardiac injury, oxidative stress and mitochondrial dysfunction in male mice

Regular waterpipe smoking (Reg-WPS) is well recognized for its deleterious effect on the heart. However, there is a paucity of experimental studies on the impact of occasional waterpipe smoking (Occ-WPS), also known as nondaily smoking, versus Reg-WPS on cardiac homeostasis, and the mechanisms underlying these effects. Hence, we aimed, in the present study, to investigate the effect of Occ-WPS (30 min/day, 1 day/week) versus Reg-WPS (30 min/day, 5 days/week) for 6 months on systolic blood pressure (SBP), cardiac injury, oxidative markers, chemokines, proinflammatory cytokines, DNA damage and mitochondrial function compared with air (control) exposed mice. Our results show that SBP was increased following exposure to either Occ-WPS or Reg-WPS compared with air-exposed mice. Moreover, we found that only Reg-WPS induced a significant elevation in the levels of troponin I, brain natriuretic peptide, lactate dehydrogenase, and creatine phosphokinase. However, the atrial natriuretic peptide (ANP) was significantly increased in both Occ-WPS and Reg-WPS groups. Compared with air-exposed mice, the levels of lipid peroxidation, reduced glutathione and monocyte chemoattractant protein-1 were only significantly augmented in the Reg-WPS. However, catalase, superoxide dismutase, and CXCL1 were significantly increased in both Occ-WPS and Reg-WPS. The concentrations of the adhesion molecules E-selectin, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1 were solely elevated in the heart of mice exposed to Reg-WPS. Similarly, the concentrations of interleukin-1β and tumor necrosis factor α were only significantly augmented in the Reg-WPS. However, both Occ-WPS and Reg-WPS triggered significant augmentation in the levels of IL17 and DNA damage compared to the control groups. Furthermore, while Occ-WPS induced a slight but statistically insignificant elevation in the concentrations of mammalian targets of rapamycin and nuclear factor erythroid-derived 2-like 2 (Nrf2) expression, Reg-WPS exposure increased their levels substantially, in addition to p53 and mitochondrial complexes II & III, and IV activities compared with air-exposed mice. In conclusion, our findings show that while the long-term Occ-WPS exposure induced an elevation of SBP, ANP, antioxidant enzymes, IL17, CXCL1, and cardiac DNA damage, Reg-WPS exposure was consistently associated with the elevation of SBP and occurrence of cardiac damage, inflammation, oxidative stress, DNA damage and mitochondrial dysfunction

Cardiac Inflammation, Oxidative Stress, Nrf2 Expression, and Coagulation Events in Mice with Experimental Chronic Kidney Disease

Chronic kidney disease (CKD) is known to be associated with cardiovascular dysfunction. Dietary adenine intake in mice is also known to induce CKD. However, in this experimental model, the mechanisms underlying the cardiotoxicity and coagulation disturbances are not fully understood. Here, we evaluated cardiac inflammation, oxidative stress, DNA damage, and coagulation events in mice with adenine (0.2% w/w in feed for 4 weeks)-induced CKD. Control mice were fed with normal chow for the same duration. Adenine increased water intake, urine output, relative kidney weight, the plasma concentrations of urea and creatinine, and the urinary concentrations of kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin. It also decreased the body weight and creatinine clearance, and caused kidney DNA damage. Renal histological analysis showed tubular dilation and damage and neutrophilic influx. Adenine induced a significant increase in systolic blood pressure and the concentrations of troponin I, tumor necrosis factor-α, and interleukin-1β in heart homogenates. It also augmented the levels of markers of lipid peroxidation measured by malondialdehyde production and 8-isoprostane, as well as the antioxidants superoxide dismutase and catalase. Immunohistochemical analysis of the hearts showed that adenine increased the expression of nuclear factor erythroid-derived 2-like 2 by cardiomyocytes. It also caused cardiac DNA damage. Moreover, compared with the control group, adenine induced a significant increase in the number of circulating platelet and shortened the thrombotic occlusion time in pial arterioles and venules in vivo, and induced a significant reduction in the prothrombin time and activated partial thromboplastin time. In conclusion, the administration of adenine in mice induced CKD-associated cardiac inflammation, oxidative stress, Nrf2 expression, and DNA damage. It also induced prothrombotic events in vivo. Therefore, this model can be satisfactorily used to study the cardiac pathophysiological events in subjects with CKD and the effect of drug treatment thereon