Unraveling the role of galectin-3 in cardiac pathology and physiology

Galectin-3 (Gal-3) is a carbohydrate-binding protein with multiple functions. Gal-3 regulates cell growth, proliferation, and apoptosis by orchestrating cell-cell and cell-matrix interactions. It is implicated in the development and progression of cardiovascular disease, and its expression is increased in patients with heart failure. In atherosclerosis, Gal-3 promotes monocyte recruitment to the arterial wall boosting inflammation and atheroma. In acute myocardial infarction (AMI), the expression of Gal-3 increases in infarcted and remote zones from the beginning of AMI, and plays a critical role in macrophage infiltration, differentiation to M1 phenotype, inflammation and interstitial fibrosis through collagen synthesis. Genetic deficiency of Gal-3 delays wound healing, impairs cardiac remodeling and function after AMI. On the contrary, Gal-3 deficiency shows opposite results with improved remodeling and function in other cardiomyopathies and in hypertension. Pharmacologic inhibition with non-selective inhibitors is also protective in cardiac disease. Finally, we recently showed that Gal-3 participates in normal aging. However, genetic absence of Gal-3 in aged mice exacerbates pathological hypertrophy and increases fibrosis, as opposed to reduced fibrosis shown in cardiac disease. Despite some gaps in understanding its precise mechanisms of action, Gal-3 represents a potential therapeutic target for the treatment of cardiovascular diseases and the management of cardiac aging. In this review, we summarize the current knowledge regarding the role of Gal-3 in the pathophysiology of heart failure, atherosclerosis, hypertension, myocarditis, and ischemic heart disease. Furthermore, we describe the physiological role of Gal-3 in cardiac aging

Right Ventricular Dysfunction following Acute Myocardial Infarction in the Absence of Pulmonary Hypertension in the Mouse

Background Cardiac remodelling after AMI is characterized by molecular and cellular mechanisms involving both the ischemic and non-ischemic myocardium. The extent of right ventricular (RV) dilatation and dysfunction and its relation to pulmonary hypertension (PH) following AMI are unknown. The aim of the current study was to evaluate changes in dimensions and function of the RV following acute myocardial infarction (AMI) involving the left ventricle (LV). Methods We assessed changes in RV dimensions and function 1 week following experimental AMI involving the LV free wall in 10 mice and assessed for LV and RV dimensions and function and for the presence and degree of PH. Results RV fractional area change and tricuspidal annular plane systolic excursion significantly declined by 33% (P = 0.021) and 28% (P = 0.001) respectively. Right ventricular systolic pressure measured invasively in the mouse was within the normal values and unchanged following AMI. Conclusion AMI involving the LV and sparing the RV induces a significant acute decline in RV systolic function in the absence of pulmonary hypertension in the mouse indicating that RV dysfunction developed independent of changes in RV afterload

Silicic conduits as supersized tuffisites:Clastogenic influences on shifting eruption styles at Cordón Caulle volcano (Chile)

Understanding the processes that drive explosive-effusive transitions during large silicic eruptions is crucial to hazard mitigation. Conduit models usually treat magma ascent and degassing as a gradual, unidirectional progression from bubble nucleation through magmatic fragmentation. However, there is growing evidence for the importance of bi-directional clastogenic processes that sinter fragmented materials into coherent clastogenic magmas. Bombs that were ejected immediately before the first emergence of lava in the 2011–2012 eruption at Cordón Caulle volcano (Chile) are texturally heterogeneous composite assemblages of welded pyroclastic material. Although diverse in density and appearance, SEM and X-ray tomographic analysis show them all to have been formed by multi-generational viscous sintering of fine ash. Sintering created discrete clasts ranging from obsidian to pumice and formed a pervasive clast-supporting matrix that assembled these clasts into a conduit-sealing plug. An evaluation of sintering timescales reveals texturally disparate bomb components to represent only minutes of difference in residence time within the conduit. Permeability modelling indicates that the plug was an effective conduit seal, with outgassing potential—even from high-porosity regions—being limited by the inability of gas to flow across tendrils of densely sintered inter-clast matrix. Contrary to traditional perspectives, declining expressions of explosivity at the surface need not be preceded or accompanied by a decline in fragmentation efficiency. Instead, they result from tips in balance between the opposing processes of fragmentation and sintering that occur in countless cycles within volcanic conduits. These processes may be particularly enhanced at silicic fissure volcanoes, which have laterally extensive subsurface plumbing systems that require complex magma ascent pathways. The textures investigated here reveal the processes occurring within silicic fissures to be phenomenologically identical to those that have been inferred to occur in tuffisite veins: silicic conduits are essentially supersized examples of edifice-penetrating tuffisites

Alterations in the Interleukin-1/Interleukin-1 Receptor Antagonist Balance Modulate Cardiac Remodeling following Myocardial Infarction in the Mouse

Background Healing after acute myocardial infarction (AMI) is characterized by an intense inflammatory response and increased Interleukin-1 (IL-1) tissue activity. Genetically engineered mice lacking the IL-1 receptor (IL-1R1-/-, not responsive to IL-1) or the IL-1 receptor antagonist (IL-1Ra, enhanced response to IL-1) have an altered IL-1/IL-1Ra balance that we hypothesize modulates infarct healing and cardiac remodeling after AMI. Methods IL-1R1-/- and IL-1Ra-/- male mice and their correspondent wild-types (WT) were subjected to permanent coronary artery ligation or sham surgery. Infarct size (trichrome scar size), apoptotic cell death (TUNEL) and left ventricular (LV) dimensions and function (echocardiography) were measured prior to and 7 days after surgery. Results When compared with the corresponding WT, IL-1R1-/- mice had significantly smaller infarcts (−25%), less cardiomyocyte apoptosis (−50%), and reduced LV enlargement (LV end-diastolic diameter increase [LVEDD], −20%) and dysfunction (LV ejection fraction [LVEF] decrease, −50%), whereas IL-1Ra-/- mice had significantly larger infarcts (+75%), more apoptosis (5-fold increase), and more severe LV enlargement (LVEDD increase,+30%) and dysfunction (LVEF decrease, +70%)(all P values \u3c0.05). Conclusions An imbalance in IL-1/IL-1Ra signaling at the IL-1R1 level modulates the severity of cardiac remodeling after AMI in the mouse, with reduced IL-1R1 signaling providing protection and unopposed IL-1R1 signaling providing harm

Unexpected large eruptions from buoyant magma bodies within viscoelastic crust

Large volume effusive eruptions with relatively minor observed precursory signals are at odds with widely used models to interpret volcano deformation. Here we propose a new modelling framework that resolves this discrepancy by accounting for magma buoyancy, viscoelastic crustal properties, and sustained magma channels. At low magma accumulation rates, the stability of deep magma bodies is governed by the magma-host rock density contrast and the magma body thickness. During eruptions, inelastic processes including magma mush erosion and thermal effects, can form a sustained channel that supports magma flow, driven by the pressure difference between the magma body and surface vents. At failure onset, it may be difficult to forecast the final eruption volume; pressure in a magma body may drop well below the lithostatic load, create under-pressure and initiate a caldera collapse, despite only modest precursors

Combination liposomal amphotericin B, posaconazole and oral amphotericin B for treatment of gastrointestinal Mucorales in an immunocompromised patient

Mucormycosis is a life threatening infection caused by fungi in the order Mucorales. Mucormycosis can affect any organ system with rhino-orbital-cerebral and pulmonary infections being the most predominant infection types. Gastrointestinal mucormycosis is rare and accounts for only 4–7% of all cases. Here, we present a case of invasive gastrointestinal mucormycosis in an immunocompromised host treated with systemic and topical anti-mold therapy

Galectin-1 as an Emerging Mediator of Cardiovascular Inflammation: Mechanisms and Therapeutic Opportunities

Galectin-1 (Gal-1), an evolutionarily conserved β-galactoside-binding lectin, controls immune cell homeostasis and tempers acute and chronic inflammation by blunting proinflammatory cytokine synthesis, engaging T-cell apoptotic programs, promoting expansion of T regulatory (Treg) cells, and deactivating antigen-presenting cells. In addition, this lectin promotes angiogenesis by co-opting the vascular endothelial growth factor receptor (VEGFR) 2 signaling pathway. Since a coordinated network of immunomodulatory and proangiogenic mediators controls cardiac homeostasis, this lectin has been proposed to play a key hierarchical role in cardiac pathophysiology via glycan-dependent regulation of inflammatory responses. Here, we discuss the emerging roles of Gal-1 in cardiovascular diseases including acute myocardial infarction, heart failure, Chagas cardiomyopathy, pulmonary hypertension, and ischemic stroke, highlighting underlying anti-inflammatory mechanisms and therapeutic opportunities. Whereas Gal-1 administration emerges as a potential novel treatment option in acute myocardial infarction and ischemic stroke, Gal-1 blockade may contribute to attenuate pulmonary arterial hypertension

Alpha-1 antitrypsin inhibits caspase-1 and protects from acute myocardial ischemia-reperfusion injury.

Item does not contain fulltextAlpha-1-antitrypsin (AAT) possesses anti-inflammatory and tissue-protective properties. Here, we studied the effects of exogenously administered AAT on caspase-1 activity and on the outcome of ischemia-reperfusion injury (I/R) in a mouse model of acute myocardial infarction (AMI). Adult male mice underwent 30 min of coronary artery ligation followed by reperfusion and were randomly assigned to receive clinical-grade AAT or albumin at reperfusion. Infarct size was evaluated after 1 and 7 days. Caspase-1 activity was measured in homogenates of heart tissue. Left ventricular (LV) end-diastolic diameter (EDD) and end-systolic diameter (ESD) were measured and LV fractional shortening (FS) and ejection fraction (EF) were calculated using transthoracic echocardiography. The effect of AAT on caspase-1 activity was determined in cultures of mouse HL-1 cardiomyocytes stimulated with LPS and triggered with nigericin or when HL-1 cells were exposed to simulated ischemia. AAT-treated mice had significantly smaller infarct sizes (-30% day 1 and -55% day 7) compared with mice treated with albumin. AAT treatment resulted in >90% reduction in caspase-1 activity in homogenates of hearts 24h after I/R. Seven days after AMI, AAT-treated mice exhibited a >90% smaller increase in LVEDD and LVESD and smaller reduction in LVEF. The increase in caspase-1 activity in HL-1 cells induced by LPS and nigericin or following exposure to simulated ischemia was reduced by >80% and AAT similarly reduced cell death by >50%. In conclusion, exogenous administration of clinical grade AAT reduces caspase-1 activity in the ischemic myocardium leading to preservation of viable myocardium and prevention of adverse cardiac remodeling.1 augustus 201