Cross-talk between lipoproteins and inflammation : The role of microvesicles

Atherothrombosis is the principal underlying cause of cardiovascular disease (CVD). Microvesicles (MV) are small blebs originated by an outward budding at the cell plasma membranes, which are released in normal conditions. However, MV release is increased in pathophysiologic conditions such as CVD. Low density lipoprotein (LDL) and MV contribute to atherothrombosis onset and progression by promoting inflammation and leukocyte recruitment to injured endothelium, as well as by increasing thrombosis and plaque vulnerability. Moreover, (oxidized)LDL induces MV release and vice-versa, perpetuating endothelium injury leading to CVD progression. Therefore, MV and lipoproteins exhibit common features, which should be considered in the interpretation of their respective roles in the pathophysiology of CVD. Understanding the pathways implicated in this process will aid in developing novel therapeutic approaches against atherothrombosis

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

Relevance of sex-differenced analyses in bioenergetics and nutritional studies

Sex-biased analyses still remain as one of the biggest limitations to obtain universal conclusions. In biomedicine, the majority of experimental analyses and a significant amount of patient-derived cohort studies exclusively included males. In nutritional and molecular medicine, sex-influence is also frequently underrated, even considering maternal-inherited organelles such as mitochondria. We herein illustrate with in-house original data examples of how sex influences mitochondrial homeostasis, review these topics and highlight the consequences of biasing scientific analyses excluding females as differentiated entities from males

Functional And Cognitive Decline Is Associated With Increased Endothelial Cell Inflammation And Platelet Activation. Liquid Biopsy Of Microvesicles In Community-Dwelling Octogenarians.

Increased life expectancy is usually associated with comorbidities, such as cardio andcerebrovascular disease causing impaired functionality. A common underlying cause ofthese comorbidities is vascular inflammation and injury. Elevated levels of circulatingmicrovesicles (cMV), as a product of a hemostatic and inflammatory cell activation,could be direct mapping of an imbalanced hemostasis. In this manuscript, we aimedto investigate by liquid biopsy whether successful aging can be discriminated bycMV levels and phenotype. To this purpose, we included 135 community-dwellingoctogenarians in a cross-sectional study. Successful aging was defined as goodfunctional (Barthel Index>90 points, and Lawton index score>7/4 points forwomen and men, respectively) and cognitive status (Spanish version of the Mini-Mental State Examination -MEC->24 points) and no need for institutionalization.Total, annexin V positive (AV+), and AV−cMV from different cell origins from thevascular compartment were phenotypically characterized and quantified from fastingplasma samples by flow cytometry. Successful aging was associated with lowerplasma concentrations of total and AV+CD141+/CD41+-CD61+, and PAC1+/AV+,CD141+/AV+, and CD36+/AV−cMV. From these phenotypes, ROC curve analysesrevealed that CD141+/AV+and CD141+/CD41+-CD61+/AV+endothelial- and platelet-derived cMV discriminate successful and non-successful aging with an AUC (95%CI) of0.655 (0.551, 0.758),P= 0.005, and 0.638 (0.535, 0.741),P= 0.013, respectively. In conclusion, successful aging is associated with low levels of cMV released by endothelialcells and platelets, indicating lower endothelial cell inflammation and platelet activation.Our results contribute to the understanding of the link between unsuccessful aging,cognitive decline and vascular cell inflammatory disturbances

High adherence to the nordic diet is associated with lower levels of total and platelet-derived circulating microvesicles in a norwegian population

Circulating microvesicles (cMV) are small phospholipid-rich blebs shed from the membrane of activated vascular cells that contribute to vascular disease progression. We aimed to investigate whether the quality of the Nordic diet is associated with the degree of blood and vascular cell activation measured by MV shedding in elderly patients after an acute myocardial infarction (AMI). One-hundred and seventy-four patients aged 70-82 years were included in this cross-sectional study. Fasting blood samples were taken within 2 to 8 weeks after an AMI. Annexin V (AV) cMV derived from blood and vascular cells were measured through flow cytometry. A patient's usual diet was recorded with the SmartDiet® questionnaire. Patients with higher adherence to the Nordic diet (highest diet score) had lower levels of total AV and platelet-derived (CD61/AV and CD31/AV) cMV. Dietary habits influence cellular activation. A high adherence to the Nordic diet (assessed by the SmartDiet® score) in elderly post-AMI patients was associated with lower levels of platelet activation, which was reflected by a lesser release of MV carrying platelet-derived epitopes, potentially contributing to an explanation of the cardioprotective effects of the Nordic diet

A comprehensive characterisation of beer polyphenols by high resolution mass spectrometry (LC-ESI-LTQ-Orbitrap-MS)

Beer is the second most consumed alcoholic beverage in Europe and shown by the European Prospective Investigation into Cancer and Nutrition cohort study to be the main food contributor to hydroxybenzoic acid intake. About 70-80% of the total polyphenol content in beer comes from malt, and the remaining 30-20% from hops. In this work, liquid chromatography coupled with an electrospray ionization hybrid linear ion trap quadrupole Orbitrap mass spectrometry technique has been used for an accurate identification of beer polyphenols. 47 phenolic compounds were identified using high mass accuracy and confirmed by MS(2) experiments, including simple phenolic acids, hydroxycinnamoylquinics, flavanols, flavonols, flavones, alkylmethoxyphenols, alpha- and iso-alpha-acids, hydroxyphenylacetic acids and prenylflavonoids. As far as we know, 7 of these compounds have been recognised in beer for the first time: feruloylquinic acid, caffeic acid-O-hexoside, coumaric acid-O-hexoside, sinapic acid-O-hexoside, catechin-O-dihexoside, kaempferol-O-hexoside, and apigenin-C-hexoside-pentoside

Total carotene plasma concentrations are inversely associated with atherosclerotic plaque burden: A post-hoc analysis of the DIABIMCAP cohort

Background and aims: Atherosclerosis is the major risk factor for cardiovascular disease (CVD), the first cause of death worldwide. Chronic low-grade inflammation and a sustained oxidative milieu are causatively related to atherosclerosis onset and progression, and therefore, dietary patterns rich in bioactive compounds with anti-inflammatory and antioxidant activities might likely contribute to revert or slowing the progression of atherosclerosis. The aim of this study is to analyse the association between fruit and vegetables intake, quantitatively measured through carotene plasma concentrations, and atherosclerotic burden, as a surrogate biomarker of CVD, in free-living subjects from the DIABIMCAP cohort study. Methods: The 204 participants of the DIABIMCAP Study cohort (Carotid Atherosclerosis in Newly Diagnosed Type 2 Diabetic Individuals, ClinicalTrials.gov Identifier: NCT01898572), were included in this cross-sectional study. Total, α-, and β-carotenes were quantified by HPLC-MS/MS. Lipoprotein analysis in serum was performed by 2D- 1H NMR- DOSY, and atherosclerosis and intima media thickness (IMT) were measured through standardized bilateral carotid artery ultrasound imaging. Results: Subjects with atherosclerosis (n = 134) had lower levels of large HDL particles than subjects without atherosclerosis. Positive associations were found between α-carotene and both large and medium HDL particles, and inverse associations were found between β- and total carotene, and VLDL and its medium/small particles. Subjects with atherosclerosis presented significantly lower plasma concentrations of total carotene compared with subjects without atherosclerosis. Plasma concentrations of carotene decreased as the number of atherosclerotic plaques increased, although after multivariate adjustment, the inverse association between β- and total carotene with plaque burden remained significant only in women. Conclusions: A diet rich in fruit and vegetables results in higher plasmatic carotene concentrations, which are associated with a lesser atherosclerotic plaque burden. © 2023 The Author(s)</p

Thrombotic complications in patients with COVID-19 : pathophysiological mechanisms, diagnosis, and treatment

Introduction Emerging evidence points to an association between severe clinical presentation of COVID-19 and increased risk of thromboembolism. One-third of patients hospitalized due to severe COVID-19 develops macrovascular thrombotic complications, including venous thromboembolism, myocardial injury/infarction and stroke. Concurrently, the autopsy series indicate multiorgan damage pattern consistent with microvascular injury. Prophylaxis, diagnosis and treatment COVID-19 associated coagulopathy has distinct features, including markedly elevated D-dimers concentration with nearly normal activated partial thromboplastin time, prothrombin time and platelet count. The diagnosis may be challenging due to overlapping features between pulmonary embolism and severe COVID-19 disease, such as dyspnoea, high concentration of D-dimers, right ventricle with dysfunction or enlargement, and acute respiratory distress syndrome. Both macro- and microvascular complications are associated with an increased risk of in-hospital mortality. Therefore, early recognition of coagulation abnormalities among hospitalized COVID-19 patients are critical measures to identify patients with poor prognosis, guide antithrombotic prophylaxis or treatment, and improve patients’ clinical outcomes. Recommendations for clinicians Most of the guidelines and consensus documents published on behalf of professional societies focused on thrombosis and hemostasis advocate the use of anticoagulants in all patients hospitalized with COVID-19, as well as 2-6 weeks post hospital discharge in the absence of contraindications. However, since there is no guidance for deciding the intensity and duration of anticoagulation, the decision-making process should be made in individual-case basis. Conclusions Here, we review the mechanistic relationships between inflammation and thrombosis, discuss the macrovascular and microvascular complications and summarize the prophylaxis, diagnosis and treatment of thromboembolism in patients affected by COVID-19

Different Storing and Processing Conditions of Human Lymphocytes do not Alter P-Glycoprotein Rhodamine 123 Efflux

P-glycoprotein (Pgp), a protein codified by Multi Drug Resistance (MDR1) gene, has a detoxifying function and might influence the toxicity and pharmacokinetics and pharmacodynamics of drugs. Sampling strategies to improve Pgp studies could be useful to optimize the sensitivity and the reproducibility of efflux assays. This study aimed to compare Pgp expression and efflux activity by measuring Rhodamine123 (Rh123) retention in lymphocytes stored under different conditions, in order to evaluate the potential utility of any of the storing conditions in Pgp functionality. Our results show no change in protein expression of Pgp by confocal studies and Western blotting, nor changes at the mRNA level (qRT-PCR). No differences in Rh123 efflux by Pgp activity assays were found between fresh and frozen lymphocytes after 24 hours of blood extraction, using either of the two Pgp specific inhibitors (VP and PSC833). Different working conditions in the 24 hours post blood extraction do not affect Rh123 efflux. These results allow standardization of Pgp activity measurement in different individuals with different timing of blood sampling and in different geographic areas. ______________