Alzheimer's disease (AD) is a degenerative disorder characterized by a decreased regional cerebral blood flow (CBF). It is most likely that a reduction in CBF could displace a pathway leading to AD genesis, in so far neuron death explains a sustained

Objective— Modified lipoproteins, particularly oxidized LDLs, are believed to evoke an inflammatory response which participates in all stages of atherosclerosis. Disposal of these particles is mediated through receptors which may trigger proinflammatory signaling pathways leading to vascular injury. This study was aimed at assessing the role in atherogenesis of one of these receptors, galectin-3. Methods and Results— Galectin-3-deficient and wild-type mice were fed an atherogenic diet or standard chow for 8 months. Lesion area and length were higher in galectin-3-deficient versus wild-type mice. At the level of the aortic sinus, wild-type animals showed only fatty streaks, whereas galectin-3-deficient mice developed complex lesions, associated with extensive inflammatory changes. This was indicated by the presence of T lymphocytes with activated Th1-phenotype and by more marked monocyte-macrophage infiltration, inflammatory mediator expression, vascular cell apoptosis, and proinflammatory transcription factor activation. Increased accumulation of oxidixed LDLs and lipoxidation products and upregulation of other receptors for these compounds, including the proinflammatory RAGE, were detected in galectin-3-deficient versus wild-type mice. Conclusions— These data suggest a unique protective role for galectin-3 in the uptake and effective removal of modified lipoproteins, with concurrent downregulation of proinflammatory pathways responsible for atherosclerosis initiation and progression.

Summary We investigated the effects of isoflurane on the rabbit cardiovascular system at several end-tidal concentrations. Furthermore, because isoflurane has been reported to produce tachycardia while reducing sympathetic nervous activity and baroreflex function, we evaluated whether the chronotropic effects of isoflurane could be due to a vagal withdrawal. ECG, mean arterial pressure (MAP), and heart rate (HR) were obtained in rabbits the conscious, unsedated state and during isoflurane anesthesia by telemetric device. Measurements of pH, oxygen, carbon dioxide, plasma catecholamines, baroreflex sensitivity, and spectral analysis of HR variability were made in nonanesthetized and anesthetized animals. Isoflurane caused an increase in HR at 0.5, 1, and 1.5 minimum alveolar concentration (MAC) and a decrease in systolic and diastolic blood pressure (SBP, DBP) and MAP at 1 and 1.5 MAC. Biochemical analysis showed that isoflurane-mediated cardiovascular effects were not accompanied by any significant changes in plasma norepinephrine (NE) and epinephrine (Epi) levels. Neither were any significant differences in plasma catecholamine levels noted between anesthetized and awake animals. The analysis of spectral components of HR variability and baroreflex function indicated that isoflurane induced a marked reduction in the low- and high-frequency spectral power of HR variability and in baroreflex sensitivity. Tachycardia under isoflurane was suppressed dose dependently by the administration of clonidine or atenolol and was not influenced by bilateral vagotomy. Collectively, our results indicate that cardiovascular effects induced by isoflurane in smaller animals such as rabbits are similar to those observed in humans and other animal species. We showed that isoflurane-induced tachycardia is mainly the result of a vagal withdrawal rather than a baroreflex response, even though a marginal role of baroreflex in heart response to higher concentrations of isoflurane cannot be excluded.

Cardiovascular diseases (CVDs) are a major burden on the healthcare system: indeed, over two million new cases are diagnosed every year worldwide. Unfortunately, important drawbacks for the treatment of these patients derive from our current inability to stop the structural alterations that lead to heart failure, the common endpoint of many CVDs. In this scenario, a better understanding of the role of epigenetics – hereditable changes of chromatin that do not alter the DNA sequence itself – is warranted. To date, hyperacetylation of histones has been reported in hypertension and myocardial infarction, but the use of inhibitors for treating CVDs remains limited. Here, we studied the effect of the histone deacetylase inhibitor Givinostat on a mouse model of acute myocardial infarction. We found that it contributes to decrease endothelial-to-mesenchymal transition and inflammation, reducing cardiac fibrosis and improving heart performance and protecting the blood vessels from apoptosis through the modulatory effect of cardiac fibroblasts on endothelial cells. Therefore, Givinostat may have potential for the treatment of CVDs.