Consistent epidemiological evidence indicates that low-to-moderate alcohol consumption is inversely associated with cardiovascular event presentation, while high levels of alcohol intake are associated to increased cardiovascular risk. Little is known on the effects of moderate beer intake in the metabolic syndrome. The aim of this study is to investigate the effects of moderate and regular daily intake of beer with meals in overweight (body mass index (BMI) of 28–29.9 kg/m²) or obese class 1 (BMI of 30–35 kg/m²) individuals without other cardiovascular risk factors (dyslipidemia, type 2-diabetes, hypertension) focusing on the effects related to changes in weight, in lipoproteins and vascular endothelial function. We have performed an open, prospective two-arms longitudinal crossover study to investigate the effects associated with regular consumption (four week) of alcohol-free-beer (0 g alcohol/day) or traditional-beer (30 g alcohol/day in men and 15 g alcohol/day in women) on anthropometrical and biochemical parameters, liver and kidney function biomarkers, and vascular endothelial function. After four-week intervention with traditional and/or alcohol-free beer, BMI did not show any significant change and values for liver and kidney functions were within the normal levels. Moderate traditional beer intake did not affect lipid levels—however it significantly increased the antioxidant capacity of high density lipoprotein (HDL). In addition, apoB-depleted serum (after the four-week intervention period) showed a higher potential to promote cholesterol efflux from macrophages. Beer consumption did not induce vascular endothelial dysfunction or stiffness. In summary, our results based on a 12-week prospective study provide evidence that moderate intake of beer (traditional and alcohol-free) does not exert vascular detrimental effects nor increases body weight in obese healthy individuals. In contrast, moderate intake of beer increases the anti-oxidative properties of HDL and facilitates cholesterol efflux, which may prevent lipid deposition in the vessel wall.

Metabolic syndrome (MetS) is a complex cluster of interrelated metabolic disorders that significantly elevate the risk of cardiovascular disease, making it a pressing public health concern worldwide. Among the key features of MetS, dyslipidemia—characterized by altered levels of high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG)—plays a crucial role in the disorder’s progression. This review aims to elucidate the intricate interplay between HDL-C and TG within the context of lipid metabolism and cardiovascular health, while also addressing the detrimental impact of various cardiovascular risk factors and associated comorbidities. The dynamics of HDL-C and TG are explored, highlighting their reciprocal relationship and respective contributions to the pathophysiology of MetS. Elevated levels of TGs are consistently associated with reduced concentrations of HDL-C, resulting in a lipid profile that promotes the development of vascular disease. Specifically, as TG levels rise, the protective cardiovascular effects of HDL-C are diminished, leading to the increased accumulation of pro-atherogenic TG-rich lipoproteins and low-density lipoprotein particles within the vascular wall, contributing to the progression of atheromas, which can ultimately result in significant ischemic cardiovascular events. Ultimately, this paper underscores the significance of HDL and TG as essential targets for therapeutic intervention, emphasizing their potential in effectively managing MetS and reducing cardiovascular risk.

Objective: HDL (high-density lipoprotein) role in atherosclerosis is controversial. Clinical trials with CETP (cholesterylester transfer protein)-inhibitors have not provided benefit. We have shown that HDL remodeling in hypercholesterolemia reduces HDL cardioprotective potential. We aimed to assess whether hypercholesterolemia affects HDL-induced atherosclerotic plaque regression. Approach and Results: Atherosclerosis was induced in New Zealand White rabbits for 3-months by combining a high-fat-diet and double-balloon aortic denudation. Then, animals underwent magnetic resonance imaging (basal plaque) and randomized to receive 4 IV infusions (1 infusion/wk) of HDL isolated from normocholesterolemic (NC-HDL; 75 mg/kg; n=10), hypercholesterolemic (HC-HDL; 75 mg/Kg; n=10), or vehicle (n=10) rabbits. Then, animals underwent a second magnetic resonance imaging (end plaque). Blood, aorta, and liver samples were obtained for analyses. Follow-up magnetic resonance imaging revealed that NC-HDL administration regressed atherosclerotic lesions by 4.3%, whereas, conversely, the administration of HC-HDLs induced a further 6.5% progression ( P <0.05 versus basal). Plaque characterization showed that HC-HDL administered animals had a 2-fold higher lipid and cholesterol content versus those infused NC-HDL and vehicle ( P <0.05). No differences were observed among groups in CD31 levels, nor in infiltrated macrophages or smooth muscle cells. Plaques from HC-HDL administered animals exhibited higher Casp3 (caspase 3) content ( P <0.05 versus vehicle and NC-HDL) whereas plaques from NC-HDL infused animals showed lower expression of Casp3, Cox1 (cyclooxygenase 1), inducible nitric oxide synthase, and MMP (metalloproteinase) activity ( P <0.05 versus HC-HDL and vehicle). HDLs isolated from animals administered HC-HDL displayed lower antioxidant potential and cholesterol efflux capacity as compared with HDLs isolated from NC-HDL-infused animal and vehicle or donor HDL ( P <0.05). There were no differences in HDL-ApoA1 content, ABCA1 (ATP-binding cassette transporter A1) vascular expression, and SRB1 (scavenger receptor B1) and ABCA1 liver expression. Conclusions: HDL particles isolated from a hypercholesterolemic milieu lose their ability to regress and stabilize atherosclerotic lesions. Our data suggest that HDL remodeling in patients with co-morbidities may lead to the loss of HDL atheroprotective functions.

Background Extracellular vesicles (EVs), shed in response to cell activation, stress, or injury, are increased in the blood of patients with cardiovascular disease. EVs are characterized by expressing parental-cell antigens, allowing the determination of their cellular origin. Platelet-derived EVs (pEVs) are the most abundant in blood. Although not universally given, EVs generally express phosphatidylserine (PS) in their membrane. Objectives To investigate pEVs in chronic and acute conditions, such as chronic heart failure (CHF) and first-onset acute coronary syndrome (ACS), in patients treated as per guidelines. Methods EVs in CHF patients (n = 119), ACS patients (n = 58), their respective controls (non-CHF [n = 21] and non-ACS [n = 24], respectively), and a reference control group (n = 31) were characterized and quantified by flow cytometry, using monoclonal antibodies against platelet antigens, and annexin V (AV) to determine PS exposure. Results CHF patients had higher EVs-PS⁻ numbers, while ACS had predominantly EVs-PS⁺. In contrast to ACS, CHF patients had significantly reduced numbers of pEVs carrying PECAM and α_IIb-integrin epitopes (CD31⁺/AV⁺, CD41a⁺/AV⁺, and CD31⁺/CD41a⁺/AV⁺), while no differences were observed in P-selectin-rich pEVs (CD62P⁺/AV⁺) compared with controls. Additionally, background etiology of CHF (ischemic vs. nonischemic) or ACS type (ST-elevation myocardial infarction [STEMI] vs. non-STEMI [NSTEMI]) did not affect pEV levels. Conclusion PS exposure in EV and pEV-release differ between CHF and ACS patients, with tentatively different functional capacities beyond coagulation to inflammation and cross-talk with other cell types. L.B., T.P., S.M., and A.C. designed the research. A.V.-F. performed experiments. A.V.-F., T.P., and L.B. analyzed the results. A.V.-F., N.M.-G., A.C., R.S., S.M., T.P., and L.B. wrote and revised the manuscript. Received: 01 December 2022 Accepted: 14 March 2023 Article published online: 19 April 2023 © 2023. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Inflammasomes are key components of the innate immunity system that trigger the inflammatory response. Inappropriate activity of the inflammasome system has been linked to onset and perpetuation of inflammation in atherosclerotic plaques and cardiovascular disease. Low-to-moderate beer consumption is inversely associated with cardiovascular event presentation, while high levels of alcohol intake are associated with increased cardiovascular risk. Although fermented beverages have been suggested to exert their beneficial effects through their anti-oxidant and anti-inflammatory properties, little is known regarding the capacity of beer to modulate innate immunity cell responses. To this aim, primed or activated THP-1 macrophages were conditioned with human serum obtained from a prospective two-arms longitudinal crossover study to investigate the effect of a moderate and regular daily intake of beer, either alcohol-free or traditional, in the regulation of TLR-mediated inflammatory responses in healthy but overweight individuals. Conditioned macrophages with serum obtained after four-week intervention with alcohol-free beer significantly reduced the transcription of pro-inflammatory interleukins such as IL-1β and TNF. The serum of traditional beer consumers did not exhibit the same capacity as the serum of alcohol-free beer consumers to reduce gene expression of pro-inflammatory interleukins; however, serum from traditional beer consumers showed a regulatory effect at the protein level by significantly decreasing the intracellular protein levels of pro-IL-1β in primed macrophages and preventing cleaved-IL-1β protein release.