Descobreixen un mecanisme d'acumulació massiva de colesterol

Científics del Consell Superior d'Investigacions Científiques i de l'Institut Català de Ciències Cardiovasculars han descobert el receptor responsable de la captació selectiva de colesterol esterificat en la paret vascular. Aquest tipus de colesterol s'acumula en l'organisme i pot agreujar les lesions vasculars fins a generar en trombosi.Científicos del Consejo Superior de Investigaciones Científicas (CSIC) ydel Instituto Catalán de Ciencias Cardiovasculares (ICCC) handescubierto el receptor responsable de la captación selectiva decolesterol esterificado en la pared vascular. Este tipo de colesterol seacumula en el organismo en forma de pequeñas gotas de grasa quepueden agravar las lesiones vasculares hasta generar una trombosis.Researchers of the Spanish National Research Council and CatalanInstitute of Cardiovascular Sciences have discovered the receiverresponsible for the selective collection of esterified cholesterol in thevascular wall. This type of cholesterol is accumulated in the organismlike small drops of fat that can aggravate the vascular injuries andgenerate thrombosis

Atherosclerosis and Thrombosis: Insights from Large Animal Models

Atherosclerosis and its thrombotic complications are responsible for remarkably high numbers of deaths. The combination of in vitro, ex vivo, and in vivo experimental approaches has largely contributed to a better understanding of the mechanisms underlying the atherothrombotic process. Indeed, different animal models have been implemented in atherosclerosis and thrombosis research in order to provide new insights into the mechanisms that have already been outlined in isolated cells and protein studies. Yet, although no model completely mimics the human pathology, large animal models have demonstrated better suitability for translation to humans. Indeed, direct translation from mice to humans should be taken with caution because of the well-reported species-related differences. This paper provides an overview of the available atherothrombotic-like animal models, with a particular focus on large animal models of thrombosis and atherosclerosis, and examines their applicability for translational research purposes as well as highlights species-related differences with humans

DJ-1 interacts with the ectopic ATP-synthase in endothelial cells during acute ischemia and reperfusion

Altres ajuts: Ministerio de Ciencia e Innovación. BES Pre-doctoral fellowship (BES-2017-081378).Endothelial cells (ECs) play a central role in ischemia. ATP-Synthase is now recognized to be ectopically expressed in the cell surface of many cell types, with putative roles described in angiogenesis, proliferation, and intracellular pH regulation. DJ-1 is a multifunctional protein, involved in cell protection against ischemia, ischemia-reperfusion (I/R), and oxidative stress, that regulates mitochondrial ATP-synthase. Here we focused on the characterization of the endothelial dynamics of DJ-1, and its implication in the regulation of the ectopic ATP-synthase (ecATP-S) activity, during acute ischemia and I/R in ECs. We found that DJ-1 is secreted from ECs, by a mechanism enhanced in ischemia and I/R. A cleaved form of DJ-1 (DJ-1∆C) was found only in the secretome of ischemic cells. The ecATP-S activity increased following acute ischemia in ECs, coinciding with DJ-1 and DJ-1∆C secretion. The inhibition of DJ-1 expression inhibited the ecATP-S response to ischemia by ∼ 50%, and its exogenous administration maximized the effect, together with an enhanced Akt phosphorylation and angiotube-formation potential at reperfusion. Immunoprecipitation studies showed direct interaction between DJ-1 and the ecATP-S. Altogether suggesting that DJ-1 is actively cleaved and released from ischemic ECs and plays an important role in the regulation of the ecATP-S activity during acute ischemia and reperfusion

Antithrombotic therapy after myocardial reperfusion in acute myocardial infarction

AbstractThe problem of post-thrombolytic reocclusion can be approached in several ways. 1) Better thrombolytic agents with longer duration of effects and more powerful properties aimed at enhanced clot lysis and anticoagulation are under study. 2) The combination of high dose heparin and low dose aspirin is proposed for all patients with an acute myocardial infarction treated with thrombolytic agents. 3) Peptide inhibitors of thrombin and monoclonal antibodies against platelet glycoprotein receptors and adhesive macromolecules are potentially effective inhibitors of platelet aggregation and thrombus formation during or after thrombolytic therapy

Benefits and risks of moderate alcohol consumption on cardiovascular disease : Current findings and controversies

Alcohol has a hormetic physiological behavior that results in either increased or decreased cardiovascular risk depending on the amount consumed, drinking frequency, pattern of consumption, and the outcomes under study or even the type of alcoholic beverage consumed. However, the vast majority of studies elucidating the role of alcohol in cardiovascular and in the global burden of disease relies on epidemiological studies of associative nature which carry several limitations. This is why the cardiovascular benefits of low-moderate alcohol consumption are being questioned and perhaps might have been overestimated. Thus, the aim of this review was to critically discuss the current knowledge on the relationship between alcohol intake and cardiovascular disease. Besides new evidence associating low and moderate alcohol consumption with decreased risk of cardiovascular disease, several questions remain unanswered related to the concrete amount of safe consumption, the type of alcoholic beverage, and the age-, sex-, and genetic/ethnical-specific differences in alcohol consumption

Effects of Polyphenol Intake on Metabolic Syndrome: Current Evidences from Human Trials

Metabolic syndrome (MetS) is a cluster of cardiovascular risk factors which severely increases the risk of type II diabetes and cardiovascular disease. Several epidemiological studies have observed a negative association between polyphenol intake and MetS rates. Nevertheless, there are relatively small numbers of interventional studies evidencing this association. This review is focused on human interventional trials with polyphenols as polyphenol-rich foods and dietary patterns rich in polyphenols in patients with MetS. Current evidence suggests that polyphenol intake has the potential to alleviate MetS components by decreasing body weight, blood pressure, and blood glucose and by improving lipid metabolism. Therefore, high intake of polyphenol-rich foods such as nuts, fruits, vegetables, seasoning with aromatic plants, spices, and virgin olive oil may be the cornerstone of a healthy diet preventing the development and progression of MetS, although there is no polyphenol or polyphenol-rich food able to influence all MetS features. However, inconsistent results have been found in different trials, and more long-term randomized trials are warranted to develop public health strategies to decrease MetS rates

Unraveling the complexity of hdl remodeling : On the hunt to restore hdl quality

Altres ajuts: European Regional Development Fund (FEDER)Increasing evidence has cast doubt over the HDL-cholesterol hypothesis. The complexity of the HDL particle and its proven susceptibility to remodel has paved the way for intense molecular investigation. This state-of-the-art review discusses the molecular changes in HDL particles that help to explain the failure of large clinical trials intending to interfere with HDL metabolism, and details the chemical modifications and compositional changes in HDL-forming components, as well as miRNA cargo, that render HDL particles ineffective. Finally, the paper discusses the challenges that need to be overcome to shed a light of hope on HDL-targeted approaches

New factors in heart failure pathophysiology : Immunity cells release of extracellular vesicles

Leukocyte-shed extracellular vesicles (EVs) can play effector roles in the pathophysiological mechanisms of different diseases. These EVs released by membrane budding of leukocytes have been found in high amounts locally in inflamed tissues and in the circulation, indicating immunity cell activation. These EVs secreted by immune cell subsets have been minimally explored and deserve further investigation in many areas of disease. In this study we have investigated whether in heart failure there is innate and adaptive immune cell release of EVs. Patients with chronic heart failure (cHF) (n = 119) and in sex- and age-matched controls without this chronic condition (n = 60). Specifically, EVs were quantified and phenotypically characterized by flow cytometry and cell-specific monoclonal antibodies. We observed that even in well medically controlled cHF patients (with guideline-directed medical therapy) there are higher number of blood annexin-V + (phosphatidylserine +)-EVs carrying activated immunity cell-epitopes in the circulation than in controls (p < 0.04 for all cell types). Particularly, EVs shed by monocytes and neutrophils (innate immunity) and by T-lymphocytes and natural-killer cells (adaptive immunity) are significantly higher in cHF patients. Additionally, EVs-shed by activated leukocytes/neutrophils (CD11b +, p = 0.006; CD29 + /CD15 +, p = 0.048), and T-lymphocytes (CD3 + /CD45 +, p < 0.02) were positively correlated with cHF disease severity (NYHA classification). Interestingly, cHF patients with ischemic etiology had the highest levels of EVs shed by lymphocytes and neutrophils (p < 0.045, all). In summary, in cHF patients there is a significant immune cell activation shown by high-release of EVs that is accentuated by clinical severity of cHF. These activated innate and adaptive immunity cell messengers may contribute by intercellular communication to the progression of the disease and to the common affectation of distant organs in heart failure (paracrine regulation) that contribute to the clinical deterioration of cHF patients

La teràpia antiplaquetar : clau per al tractament de l'aterotrombosis coronària

El futur en el tractament de la isquèmia coronària i de la seva patologia més perillosa, l'aterotrombosis, dependrà de les millores en la investigació. Enfront d'una malaltia de la qual encara es desconeix el tractament definitiu, la detecció i control de les plaques d'ateroma en les artèries és el primer pas, i el més important. Per això, potenciar els medicaments en ús i descobrir agents alternatius dintre dels esquemes antiplaquetaris que ja estan marcats, podrà donar llum al tractament d'una afecció que ja és la responsable del major nombre de morts prematures de l'home actual

Network-Assisted Systems Biology Analysis of the Mitochondrial Proteome in a Pre-Clinical Model of Ischemia, Revascularization and Post-Conditioning

Altres ajuts: Ministerio de Ciencia e Innovación; Fundación de Investigación Cardiovascular-Fundación Jesús Serra.Infarct size is the major risk predictor for developing heart failure after an acute myocardial infarction (AMI). The discovery of the conditioning phenomena (i.e., repetitive brief cycles of ischemia applied either before or after a prolonged ischemic insult) has highlighted the existence of endogenous protective mechanisms of the heart potentially limiting infarct size after revascularization. However, most cardioprotective strategies, aiming at infarct size reduction, have failed in clinical studies. Thus, cardioprotection is an unmet clinical need. In the present study, we took a network-assisted systems biology approach to explore the mitochondrial proteomic signature of the myocardium after ischemia, ischemia with direct revascularization, and ischemia with re-establishment of blood flow by postconditioning in a swine model of AMI. Furthermore, network extension with the ENCODE project human regulatory data allowed the prediction of potential transcription factors at play in the response to post-conditioning of the myocardium. Collectively, our results identify cardiac metabolism as a driver of cardioprotection, highlighting a dual role for post-conditioning promoting metabolic reprogramming of the myocardium, and a protective response mediated by VDAC2 and DJ-1 in the mitochondria