Vascular and Platelet Effects of Tomato Soffritto Intake in Overweight and Obese Subjects.

Tomatoes are known for their numerous health benefits, including antioxidants, anti-cancer, antimicrobial, anti-inflammatory, anti-neurodegenerative, antiplatelet, and cardio-protective properties. However, their potential health benefits in the Mediterranean diet's popular soffritto remain largely unexplored in scientific research. The objective was to evaluate the effects of soffritto intake on platelet activity, vascular endothelial function, weight, lipid profile, and blood parameters. In a prospective, controlled, randomized two-arm longitudinal cross-over trial, 40 overweight and obese individuals received 100 g/day of soffritto, or a control, for 42 days. The primary outcome was the effect on vascular endothelial function and platelet activity. As exploratory secondary outcomes, anthropometric measures, serum lipid profile, and hemogram profile were measured before and after a 6-week intervention with or without soffritto supplementation. Compared with the control group, soffritto supplementation for six weeks improved collagen-induced (-5.10 ± 3.06%) platelet aggregation (p < 0.05). In addition, after six weeks, a reduction in ADP-induced aggregation (-3.67 ± 1.68%) was also only observed in the soffritto group (p < 0.05). No significant effects of the soffritto intake were observed on vascular endothelial function, anthropometric measures, serum lipid profile, or blood parameters (p > 0.05). In conclusion, as a basic culinary technique, soffritto may have a role in the primary prevention of cardiovascular disease by reducing platelet activation, which could contribute to a reduction in thrombotic events.

Platelet-Released Extracellular Vesicle Characteristics Differ in Chronic and in Acute Heart Disease.

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 αIIb-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.

Dysfunctional antioxidant capacity of high-density lipoprotein in rheumatoid arthritis.

BACKGROUND: High-density lipoprotein (HDL) presents atheroprotective functions not readily reflected by plasma HDL-cholesterol levels. The aim of this study was to investigate HDL antioxidant function in patients with rheumatoid arthritis (RA). METHODS: This pilot and cross-sectional study included 50 RA patients and 50 controls matched by age, gender, cardiovascular risk factors and drug therapy. The antioxidant capacity of HDL was assessed by the total radical-trapping antioxidative potential test (TRAP-assay) and the susceptibility of low-density lipoprotein (LDL) to oxidation by the Conjugated Dienes Assay (Dmax ). A carotid ultrasound was performed in all participants to detect subclinical atherosclerosis. RESULTS: High-density lipoprotein from RA patients showed lower antioxidant capacity than those from controls [oxidized-LDL%: 35.8 (27-42) vs. 24.4 (20-32), p < .001] when analysed with the TRAP-assay. In addition, the time to achieve 50% of maximal LDL oxidation (Lag-time) was shorter in RA-patients than in matched controls [57.2 (42-71) vs. 69.5 (55-75) minutes, (p = .003)]. RA patients showed a higher atherosclerotic burden than controls. The pro-oxidant pattern in RA was irrespective of the presence of carotid atherosclerosis. On the contrary, there was a positive correlation between inflammatory parameters (erythrocyte sedimentation rate, ultrasensitive C-reactive protein and fibrinogen) and the loss of HDL-anti-oxidant capacity measured by the TRAP-assay (rho = .211, p = .035; rho = .231, p = .021 and rho = .206, p = .041, respectively). Furthermore, the glucocorticoid dose at recruitment was negatively associated with the Lag-time in RA patients (rho = -.387, p = .026). CONCLUSION: Rheumatoid arthritis patients present reduced HDL antioxidant capacity and a lower resistance of LDL particles to oxidation, mainly related to the degree of inflammation.

HDL Function and Size in Patients with On-Target LDL Plasma Levels and a First-Onset ACS.

Patients admitted for acute coronary syndrome (ACS) usually have high cardiovascular risk scores with low levels of high-density lipoprotein cholesterol (HDL-C) and high low-density lipoprotein cholesterol (LDL-C) levels. Here, we investigated the role of lipoprotein functionality as well as particle number and size in patients with a first-onset ACS with on-target LDL-C levels. Ninety-seven patients with chest pain and first-onset ACS with LDL-C levels of 100 ± 4 mg/dL and non-HDL-C levels of 128 ± 4.0 mg/dL were included in the study. Patients were categorized as ACS and non-ACS after all diagnostic tests were performed (electrocardiogram, echocardiogram, troponin levels and angiography) on admission. HDL-C and LDL-C functionality and particle number/size by nuclear magnetic resonance (NMR) were blindly investigated. A group of matched healthy volunteers (n = 31) was included as a reference for these novel laboratory variables. LDL susceptibility to oxidation was higher and HDL-antioxidant capacity lower in the ACS patients than in the non-ACS individuals. ACS patients had lower HDL-C and Apolipoprotein A-I levels than non-ACS patients despite the same prevalence of classical cardiovascular risk factors. Cholesterol efflux potential was impaired only in the ACS patients. ACS-STEMI (Acute Coronary Syndrome-ST-segment-elevation myocardial infarction) patients, had a larger HDL particle diameter than non-ACS individuals (8.4 ± 0.02 vs. 8.3 ± 0.02 and, ANOVA test, p = 0.004). In conclusion, patients admitted for chest pain with a first-onset ACS and on-target lipid levels had impaired lipoprotein functionality and NMR measured larger HDL particles. This study shows the relevance of HDL functionality rather than HDL-C concentration in ACS patients.

Antioxidative Effects of Rosuvastatin in Low-to-Moderate Cardiovascular Risk Subjects.

Background: Although vast clinical evidence supports the oxidative CVD hypothesis, little is known on the effects of statins on LDL/HDL oxidative functionality. Therefore, the aim of this study was to evaluate the antioxidative effects of rosuvastatin by monitoring the susceptibility of LDL to oxidation and the antioxidative HDL potential in low-to-moderate CV risk subjects. Methods: 40 adult ambulatory patients (aged 53.8±10.9 years, 27 women and 13 men) were included in the study. Data was collected from patients' records, physical examination, and blood sampling. Subjects were prescribed rosuvastatin at 20mg/day. Traditional risk-factors/indicators, lipid parameters, inflammatory/immune markers, LDL susceptibility to oxidation and HDL antioxidative potential were monitored and statistically analyzed with t-test, Chi-square test, one-way ANOVA, Mann-Whitney, and Kruskal-Wallis tests. Multivariate logistic regression analyses were made. Results were considered significant when p≤0.05. Results: 67% of the patients showed lower susceptibility of LDL to oxidation after rosuvastatin treatment (p=0.03), with no significant effect on baseline LDL oxidation and lag time. All three LDL oxidative indices were seen to be dependent on the subjects' lipid profile, hemoglobin levels and the IL-1α and IL-8 pro-inflammatory marker levels. 53% of the patients showed higher HDL antioxidative capacity after treatment, but without statistical significance (p=0.07). Increased antioxidative potential of HDL with rosuvastatin treatment was more likely in males (OR=9.350; p=0.010), and subjects achieving lower post-treatment CV relative risk levels (higher CV risk reduction) (OR=0.338; p=0.027). Conclusions: This study suggests the need of a comprehensive approach when investigating oxidative stress and LDL/HDL functions, especially in low-to-moderate CVD risk subjects.

Moderate Beer Intake Downregulates Inflammasome Pathway Gene Expression in Human Macrophages.

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-1ß 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-1ß in primed macrophages and preventing cleaved-IL-1ß protein release.

The role of triglycerides in the origin and progression of atherosclerosis.

Hypertriglyceridaemia has been associated with cardiovascular disease risk in humans for several decades. However, only recently, data from basic research, as well as from genetic and observational studies, have suggested triglyceride-rich lipoproteins (TRLs) as causal factors for atherosclerotic cardiovascular disease. Novel findings highlighting the relevance of TRL-derived lipolytic products (remnant lipoprotein particles "RLPs"), rather than plasma triglycerides or TRL themselves, as the true mediators in atherosclerosis, have contributed to explain a causal relationship through a number of direct and indirect mechanisms. Thus, experimental studies in animal models and in vitro cell culture methods reveal that RLPs, having sizes below 70-80nm, enter the arterial wall and accumulate within the sub-endothelial space. They then become involved in the cholesterol deposition of cholesterol in the intima in addition to several pro-inflammatory and pro-apoptotic pathways. In this review, a summary is presented of current understanding of the pathophysiological mechanisms by which TRLs and their lipolytic derived RLP induce the formation and progression of atherosclerotic lesions, and actively contribute to cardiovascular disease.

Sex Differences and Emerging New Risk Factors for Atherosclerosis and Its Thrombotic Complications.

Cardiovascular diseases (CVD) remain the world's leading cause of death and disability in both men and women, but with different prognostics and outcomes between sexes. Although the burden of CVD is generally related to the conventional risk factors, the relevance of non-traditional risk factors is increasingly being recognized to explain the so-called "residual risk". Men and women share many similarities regarding classical cardiovascular risk factors but have different disease pathophysiology, clinical presentations, prevalence, and outcomes of CVDs. How sex-specificities regarding the effects of non-traditional risk factors may contribute to the evolution of atherosclerosis and its clinical manifestations in males and females remain largely underanalyzed. The present review summarizes the current knowledge for sex differences in atherosclerotic plaque composition and clinical evolution in association with risk factors, such as inflammation, lipoprotein(a), hemostasis, intraplaque calcification, and depression. We further discuss the potential sex-differential impact of chronic infectious diseases, gut microbiome and, epigenetic gene expression regulation for atherosclerosis and the effect of female-specific disorders in CVD.

HDL (High-Density Lipoprotein) Remodeling and Magnetic Resonance Imaging-Assessed Atherosclerotic Plaque Burden: Study in a Preclinical Experimental Model.

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.

Moderate Beer Intake and Cardiovascular Health in Overweight Individuals.

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.

Internally displaced "victims of armed conflict" in Colombia: the trajectory and trauma signature of forced migration.

While conflict-induced forced migration is a global phenomenon, the situation in Colombia, South America, is distinctive. Colombia has ranked either first or second in the number of internally displaced persons for 10 years, a consequence of decades of armed conflict compounded by high prevalence of drug trafficking. The displacement trajectory for displaced persons in Colombia proceeds through a sequence of stages: (1) pre-expulsion threats and vulnerability, (2) expulsion, (3) migration, (4) initial adaptation to relocation, (5) protracted resettlement (the end point for most forced migrants), and, rarely, (6) return to the community of origin. Trauma signature analysis, an evidence-based method that elucidates the physical and psychological consequences associated with exposures to harm and loss during disasters and complex emergencies, was used to identify the psychological risk factors and potentially traumatic events experienced by conflict-displaced persons in Colombia, stratified across the phases of displacement. Trauma and loss are experienced differentially throughout the pathway of displacement.