Role In Cardiovascular Health Research Articles

Abstract P363: Cardiovascular Health as a Mediator of Psychosocial Influences on CVD

Background: Negative psychosocial factors, such as high stress and poor social support, are strongly associated with disease outcomes, including CVD. Conceptually, it is plausible that better cardiovascular health (CVH) may blunt the association between psychosocial factors and incident CVD. However, few studies have investigated whether CVH, which includes biological and behavioral factors, is a potential pathway between psychosocial factors and CVD. Objective: To investigate whether the association between CVD and psychosocial factors is fully or partially mediated by CVH. Setting: This study was carried out in a nationally representative sample of Canadian adults aged 20 years and older. Data and Methods: This study is a cross-sectional design using data from the Canadian Community Health Survey (CCHS) 2015-2016 database. The CCHS is a nationwide, nationally representative survey that collects information on the health status, health care utilization and health determinants of the Canadian population. The study outcome was CVD, as measured by the self-reported presence of physician-diagnosed heart disease. The potential mediator was individual CVH, defined using the AHA CVH Index (CVHI) and determined using self-reported responses in CCHS. Psychosocial factors included self-reported responses to questions on life stress, work stress, sleep, social support and alcohol and drug use. A structural equation modeling (SEM) approach was then used to explore the mediational role of CVH in the association of CVD with psychosocial factors. Analyses were conducted in MPlus Version 8 software. Results: The majority of the population were males (51%), aged 40-60 (37%), with tertiary education (64%) and of the White race (79%). Overall, the mean CVH of the population was 4.5. Results suggested that CVH and all psychosocial factors, except for life stress predicted, CVD. Additionally, all psychosocial factors, except for life stress and drug use, predicted CVH. Standardized coefficients demonstrated that, of all psychosocial factors, work stress had the highest impact on both CVH (std coeff -0.22, p<0.001) and CVD (std coeff -0.07, p<0.0001). Further analyses demonstrated that CVHI partially mediated the association between CVD and work stress (std coeff -0.02, p<0.001), sleep (std coeff -0.002, p<0.001), alcohol use (std coeff -0.009, p<0.001) and social support (std coeff -0.001, p=0.003). None of the associations were fully mediated by CVH. Conclusion: Results indicated that the association between psychosocial factors and CVD was partially mediated by CVH. That is, while better CVH weakened the association between psychosocial factors and CVD, the direct association between psychosocial factors and CVD remained. Further analyses should investigate whether accounting for individual characteristics such as age, sex and race may reveal full mediation through CVH.

Production of High-Value Polyunsaturated Fatty Acids Using Microbial Cultures.

Microbes can produce not only commodity fatty acids, such as palmitic acid (16:0) and stearic acid (18:0), but also high-value fatty acids (essential fatty acids). Most high value fatty acids belong to long chain polyunsaturated fatty acids (PUFA), such as omega-3 fatty acids (e.g., eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) and omega-6 fatty acids (e.g., arachidonic acid (ARA) and γ-linolenic acid (GLA)). EPA (20:5n-3) is a 20-carbon fatty acid with five double bonds, and the first double bond is in the n-3 position. DHA (22:6n-3) is a 22-carbon fatty acid with 6 double bonds and the first double bond is also in the n-3 position. Both EPA and DHA play an essential role in cardiovascular health including prevention of atherosclerotic disease development (Zehr and Walker, Prostaglandins Other Lipid Mediat 134:131-140, 2018). ARA (20:4n-6) is a 20-carbon fatty acid with four double bonds, and the first double bond is in the n-6 position. GLA (18:3n-6) is an 18-carbon fatty acid with three double bonds, and the first double bond is in the n-6 position. ARA and GLA have multiple biological effects, such as lowering blood cholesterol, and lowering cardiovascular mortality (Poli and Visioli, Eur J Lipid Sci Technol 117(11):1847-1852, 2015). This chapter provides details on microbial production of EAP, DHA, ARA, and GLA.

Long-Term Exposure to Ultrafine Particles and Incidence of Cardiovascular and Cerebrovascular Disease in a Prospective Study of a Dutch Cohort.

Background:There is growing evidence that exposure to ultrafine particles (UFP; particles smaller than ) may play an underexplored role in the etiology of several illnesses, including cardiovascular disease (CVD).Objectives:We aimed o investigate the relationship between long-term exposure to ambient UFP and incident cardiovascular and cerebrovascular disease (CVA). As a secondary objective, we sought to compare effect estimates for UFP with those derived for other air pollutants, including estimates from two-pollutant models.Methods:Using a prospective cohort of 33,831 Dutch residents, we studied the association between long-term exposure to UFP (predicted via land use regression) and incident disease using Cox proportional hazard models. Hazard ratios (HR) for UFP were compared to HRs for more routinely monitored air pollutants, including particulate matter with aerodynamic diameter (), PM with aerodynamic diameter (), and .Results:Long-term UFP exposure was associated with an increased risk for all incident CVD [ per ; 95% confidence interval (CI): 1.03, 1.34], myocardial infarction (MI) (; 95% CI: 1.00, 1.79), and heart failure (; 95% CI: 1.17, 2.66). Positive associations were also estimated for (; 95% CI: 1.01, 1.48 per ) and coarse PM (; HR for all ; 95% CI: 1.01, 1.45 per ). CVD was not positively associated with (HR for all ; 95% CI: 0.75, 1.28 per ). HRs for UFP and CVAs were positive, but not significant. In two-pollutant models ( and ), positive associations tended to remain for UFP, while HRs for and generally attenuated towards the null.Conclusions:These findings strengthen the evidence that UFP exposure plays an important role in cardiovascular health and that risks of ambient air pollution may have been underestimated based on conventional air pollution metrics. https://doi.org/10.1289/EHP3047

Cardioprotective Effects of Omega-3 Polyunsaturated Fatty Acids: Dichotomy between Experimental and Clinical Studies.

The high-fat diet of North Americans has a major impact on cardiovascular disease occurrence. Notably, fatty acids have been identified as important factors that could modulate such diseases, especially myocardial infarction (MI). Experimentally, omega-3 polyunsaturated fatty acids (PUFA) have demonstrated positive effects on cardiovascular disorders and have also shown cardioprotection by decreasing MI size. Although many animal experiments have clearly established the benefits of omega-3 PUFA, clinical studies have not reached similar conclusions. In fact, the findings of recent clinical investigations indicate that omega-3 PUFA play only a minor role in cardiovascular health. This dichotomy between experimental and clinical studies may be due to different parameters that are not taken into account in animal experiments. We have recently observed that the high consumption of omega-6 PUFA results in significant attenuation of the beneficial effect of omega-3 PUFA on MI. We believe that part of the dichotomy between experimental and clinical research may be related to the quantity of omega-6 PUFA ingested. This review of the data indicates the importance of considering omega-6 PUFA consumption in omega-3 PUFA studies.

Physical Activity, Immune System, and the Microbiome in Cardiovascular Disease.

Cardiovascular health is a primary research focus, as it is a leading contributor to mortality and morbidity worldwide, and is prohibitively costly for healthcare. Atherosclerosis, the main driver of cardiovascular disease, is now recognized as an inflammatory disorder. Physical activity (PA) may have a more important role in cardiovascular health than previously expected. This review overviews the contribution of PA to cardiovascular health, the inflammatory role of atherosclerosis, and the emerging evidence of the microbiome as a regulator of inflammation.

L-Arginine treatment improves angiogenic response and reduces matrix metalloproteinase activity in chronic heart failure patients with coronary artery disease

l-Arginine is an important dietary amino acid with well-established role in cardiovascular health as a precursor of NO synthesis, however its effects on angiogenesis-related proteins in coronary artery disease (CAD) are not completely known. This study was undertaken to evaluate effects of l-arginine on the levels of key angiogenic regulators and matrix metalloproteinase (MMP) activity in sera of chronic heart failure (CHF) patients with CAD. Thirty-three patients were divided into two groups: 1) received only the standard treatment (control group, n = 13); 2) received l-arginine intravenous infusions in the dose of 4.2 g /100 mL for 7 days, followed by oral supplementation in the daily dose of 6 g for 3 months (n = 20). Significant up-regulation of vascular endothelial growth factor (VEGF) was found immunochemically in sera of l-arginine-treated patients as compared to control individuals. Serum MMP-2 and -9 activities were dramatically reduced after l-arginine treatment. Decrease in circulating levels of angiostatin and degradation products of fibronectin, a predominant constituent of the endothelial basement membrane, could result from l-arginine-induced inhibition of MMP activities. Our findings indicate that l-arginine rebounds the angiogenic balance in favour of improving neovascularization that potentially contributes to cardiovascular benefits in CHF patients with CAD.

Long-term Exposure to Ultrafine Particles and Incidence of Cardiovascular and Cerebrovascular Disease

Background/Aim: Multiple lines of research have indicated that exposure to ambient air pollution (mostly measured as particulate matter less than 2.5 µm in size [PM2.5]) plays a significant role in morbidity and mortality. However, there is growing evidence that exposure to ultrafine particles (UFP – particles smaller than 100nm) may play an under-explored role in the aetiology of several illnesses, including cardiovascular disease. Methods: We studied the association between long-term exposure to UFP (predicted via land use regression) and incident cardiovascular disease using Cox proportional hazard models in a longitudinal study of 40,011 Dutch residents. Hazard ratios (HR) for UFP were compared to HRs for more routinely monitored air pollutants including PM10, PM2.5 and NO2. Results: Long-term UFP exposure was associated with an increased risk for all incident cardiovascular disease (HR: 1.18 per 10,000 particles/cm3, 95% CI: 1.03:1.34), myocardial infarction (HR: 1.34, 95% CI: 1.00:1.79), and heart failure (HR: 1.76, 95% CI 1.17:2.66). Similar findings were observed for NO2 and coarse PM (PM between 10 and 2.5 µm) but not for PM2.5. Elevated (albeit non-statistically significant) HRs for UFP exposure were also observed for cerebrovascular diseases. Two-pollutant models (UFP + NO2 and UFP + PMcoarse) identified that the elevated risk estimate remained for UFP, while results for PMcoarse and NO2 typically attenuated towards the null. Conclusions: These findings strengthen the evidence that UFP exposure plays an important role in cardiovascular health and that risks of ambient air pollution may have been underestimated based on conventional air pollution metrics such as PM2.5.

We FRET so You Don't Have To: New Models of the Lipoprotein Lipase Dimer.

Lipoprotein lipase (LPL) is a dimeric enzyme that is responsible for clearing triglyceride-rich lipoproteins from the blood. Although LPL plays a key role in cardiovascular health, an experimentally derived three-dimensional structure has not been determined. Such a structure would aid in understanding mutations in LPL that cause familial LPL deficiency in patients and help in the development of therapeutic strategies to target LPL. A major obstacle to structural studies of LPL is that LPL is an unstable protein that is difficult to produce in the quantities needed for nuclear magnetic resonance or crystallography. We present updated LPL structural models generated by combining disulfide mapping, computational modeling, and data derived from single-molecule Förster resonance energy transfer (smFRET). We pioneer the technique of smFRET for use with LPL by developing conditions for imaging active LPL and identifying positions in LPL for the attachment of fluorophores. Using this approach, we measure LPL-LPL intermolecular interactions to generate experimental constraints that inform new computational models of the LPL dimer structure. These models suggest that LPL may dimerize using an interface that is different from the dimerization interface suggested by crystal packing contacts seen in structures of pancreatic lipase.

Dietary Patterns and Retinal Vessel Caliber in the Irish Nun Eye Study

BackgroundRetinal vessel abnormalities are associated with cardiovascular disease risk. Widening of retinal venules is associated with increased risk of stroke while narrowing of retinal arterioles independently predicts incident hypertension, coronary heart disease and diabetes. Dietary factors are known to play an important role in cardiovascular health. However, few studies have examined the association between dietary patterns (DPs) and retinal microvascular health.ObjectiveTo examine the association between ‘a posteriori’- derived DPs and retinal vascular caliber (RVC) in older women with a restricted lifestyle.MethodsThis was a cross-sectional study of 1233 participants (mean age: 76.3 years) from the Irish Nun Eye Study (INES). Computer-assisted software was used to measure RVC from digital eye images using standardized protocols. Dietary intake was assessed using a food frequency questionnaire (FFQ). DP analysis was performed using principal component analysis from completed FFQs. Regression models were used to assess associations between DPs and retinal vessel diameters, adjusting for age, body mass index, refraction, hypertension, diabetes mellitus, ischemic heart disease, cerebrovascular accident and fellow eye RVC.ResultsTwo DPs were identified: a ‘healthy’ pattern with high factor loadings for fruit, vegetables, wholegrains and oily fish and an ‘unhealthy’ pattern with high factor loadings for sugar and sweets, chips, high fat dairy products and French fries. Adjusted linear regression analysis revealed that those who adhered most closely to the unhealthy DP had wider central retinal venular equivalent (CRVE) (p=0.03) and narrower central retinal arteriolar equivalent (CRAE) (p=0.01) compared to the least unhealthy DP. No independent relationship was observed between the healthy DP and RVC.ConclusionIn this cohort of older women with a restricted lifestyle, an unhealthy DP was independently associated with an unfavorable retinal profile, namely a widening of retinal venules and narrowing of retinal arterioles.

Abstract 21411: Coronary Endothelial ROS Protects Cardiac Function

Introduction: Recent findings from our lab demonstrated that modulation of NADPH oxidase-derived ROS for a short period (4 weeks), but not long period (20 weeks), improves coronary endothelial cell proliferation in vitro and aortic sprouting angiogenesis ex vivo . Hypothesis: We hypothesized that whereas short-term increase in endothelial ROS will improve post-MI cardiac function by increased coronary angiogenesis, long-term exposure to ROS will not. Methods: Tetracycline (Tet)-ON/Tet-OFF binary transgenic mice, Tet-Nox2:VE-Cad-tTA (Tg-Nox2), were used as a model for endothelium-specific increase in the expression of the catalytic subunit of NADPH oxidase resulting in increased ROS. Tet-ON and Tet-OFF Tg-Nox2 mice that were exposed to 4 weeks (short-term) and 16 weeks (long-term) of increased EC-ROS were subject to LAD ligation. Results: We demonstrate that there was an increase in capillary density (by 38± 6.45; p<0.05) and angiogenesis (by 2-fold) in short-term Tg-Nox2 post-MI myocardium but not in long-term Tg-Nox2. Short-term, but not long-term, Tg-Nox2 animals showed reduction in infarct size by Trichrome staining and improvement in cardiac function including EF, LVEDV and LVESV by echocardiography. Conclusion: These findings suggest that a short, but not long, exposure to increased EC-ROS play an important role in cardiovascular health and myocardial preservation in the post-MI heart.

İnsülin Direnci, Beslenme ve Yağlı Yeme İsteği ile CD36 Reseptörü İlişkisi

Global olarak beslenme gibi yaşam tarzındaki hızlı değişim ile birlikte insülin direnci ve diyabet prevalansı hızla artış göstermiş ve günümüzde Tip II diabetes mellitus (Tip II DM) epidemik bir sorun haline gelmiştir. Yaşam tarzı müdahalelerinden en önemlisi olan diyetin düzenlenmesi ise tip II DM‘nin ortaya çıkmasının engellenmesinde, geciktirilmesinde, komplikasyonların oluşmasında ve önlenmesinde önemli bir role sahiptir. Son yıllarda yapılan çalışmalarda Tip II DM gelişimine neden olan patolojik faktörler arasında yer alan insülin aktivitesi ve insülin sekresyonunun diyabet nedenini belirlemek açısından tek başına yetersiz kaldığı ele alınmaktadır. Buna ek olarak diyabet etiyolojisinde multi-faktöriyel nedenlerin, insülinin yanı sıra farklı reseptörlerin yer aldığı ve bu durumu genetik çalışmaların desteklediği bilinmektedir. Bu reseptörlerden biri olan CD36 reseptörü ise, kardiyovasküler sağlık ve hastalıklar, kanser, diyabet, insülin direnci, tat alma duyusu ve besin seçiminde önemli rol oynamaktadır. Yapılan çalışmalarda yüksek kan CD36 düzeylerinin tip II DM patogenezinde yeni bir belirteç olarak katkı sağlayabileceği yer almaktadır. Ayrıca güncel veriler CD36 reseptörünün yağlı besin seçimi açısından farklı tat ve kokularda görev alabildiğini göstermektedir. Bu derlemede CD36 reseptörü ile insülin direnci ve diyette yağlı besin seçimi arasında ilişki incelenmiştir.

Transgenic overexpression of GTP cyclohydrolase 1 in cardiomyocytes ameliorates post-infarction cardiac remodeling

GTP cyclohydrolase 1 (GCH1) and its product tetrahydrobiopterin play crucial roles in cardiovascular health and disease, yet the exact regulation and role of GCH1 in adverse cardiac remodeling after myocardial infarction are still enigmatic. Here we report that cardiac GCH1 is degraded in remodeled hearts after myocardial infarction, concomitant with increases in the thickness of interventricular septum, interstitial fibrosis, and phosphorylated p38 mitogen-activated protein kinase and decreases in left ventricular anterior wall thickness, cardiac contractility, tetrahydrobiopterin, the dimers of nitric oxide synthase, sarcoplasmic reticulum Ca2+ release, and the expression of sarcoplasmic reticulum Ca2+ handling proteins. Intriguingly, transgenic overexpression of GCH1 in cardiomyocytes reduces the thickness of interventricular septum and interstitial fibrosis and increases anterior wall thickness and cardiac contractility after infarction. Moreover, we show that GCH1 overexpression decreases phosphorylated p38 mitogen-activated protein kinase and elevates tetrahydrobiopterin levels, the dimerization and phosphorylation of neuronal nitric oxide synthase, sarcoplasmic reticulum Ca2+ release, and sarcoplasmic reticulum Ca2+ handling proteins in post-infarction remodeled hearts. Our results indicate that the pivotal role of GCH1 overexpression in post-infarction cardiac remodeling is attributable to preservation of neuronal nitric oxide synthase and sarcoplasmic reticulum Ca2+ handling proteins, and identify a new therapeutic target for cardiac remodeling after infarction.

Bioactive food chemicals and gastrointestinal symptoms: a focus of salicylates.

Bioactive food chemicals are substances present in food that are capable of interacting with living cells causing changes in physiological functions. Salicylic acid (SA), a plant hormone involved in plant immune response, is one such bioactive food chemical. Aspirin, a commercially available SA, might play beneficial roles in cardiovascular health and colon cancer. It may also cause urticaria, angioedema, asthma, and gastrointestinal symptoms in SA-sensitive individuals. Dietary SA might exert similar beneficial effects and/or may induce similar symptoms in hypersensitive individuals. Food-related SA sensitivity in relation to gastrointestinal symptoms is not well documented besides a few self-reported questionnaires and the knowledge that low doses of aspirin (equivalent of high dietary intake) can cause gastrointestinal injury. The only direct evidence that suggests benefits of reducing dietary SA was reported in asthmatic individuals. Although SA sensitivity in relation to gut symptoms in susceptible individuals is accepted by clinicians, the detection of this disease remains a challenge because of the complicated nature of dietary challenges and the risk of oral aspirin provocation tests in patients with severe hypersensitivity reactions. Given the non-IgE mediated nature of the disease, in vitro assays like basophil activation may have failed to produce reliable results. However, given the simplicity of this assay, further studies need to be formulated to firmly establish its reliability. Formulation of proper dietary strategies for symptom control is also impossible given the controversial and scant nature of the data on SA content of food. This issue needs to be resolved to formulate proper dietary strategies for effective symptom control.

Sleep: important considerations for the prevention of cardiovascular disease.

Sleep plays many roles in maintenance of cardiovascular health. This review summarizes the literature across several areas of sleep and sleep disorders in relation to cardiometabolic disease risk factors. Insufficient sleep duration is prevalent in the population and is associated with weight gain and obesity, inflammation, cardiovascular disease, diabetes, and mortality. Insomnia is also highly present and represents an important risk factor for cardiovascular disease, especially when accompanied by short sleep duration. Sleep apnea is a well-characterized risk factor for cardiometabolic disease and cardiovascular mortality. Other issues are relevant as well. For example, sleep disorders in pediatric populations may convey cardiovascular risks. Also, sleep may play an important role in cardiovascular health disparities. Sleep and sleep disorders are implicated in cardiometabolic disease risk. This review addresses these and other issues, concluding with recommendations for research and clinical practice.

Relative Handgrip Strength Is a Simple Indicator of Cardiometabolic Risk among Middle-Aged and Older People: A Nationwide Population-Based Study in Taiwan.

BackgroundMuscle strength may play an important role in cardiovascular health. The study was intended to evaluate the association between cardiometabolic risk, risk of coronary artery disease and handgrip strength by using the relative handgrip strength.Materials and MethodsData of 927 Taiwanese aged 53 years and older (510 men and 417 women) were retrieved from a nationwide representative population-based cohort cross-sectional study in 2006. All participants were interviewed face-to-face and received measures of anthropometry, dominant handgrip strength, relative handgrip strength (summation of both handgrip strength divided by body mass index) and serum biomarkers.ResultsMultivariate linear regression analysis showed the significant association between relative handgrip strength and favorable cardiometabolic risk factors including blood pressure, triglyceride, total cholesterol to high density cholesterol(HDL-C) ratio, glycohemoglobin (HbA1c), uric acid, Framingham risk score in men, and HDL-C, fasting glucose, HbA1c, log hsCRP in women. Dominant hand grip strength was only associated with log hsCRP in women. (p<0.05 for all), but was not significant associated with all cardiovascular biomarkers and FRS in both sex.ConclusionsJoint with handgrip strength and body size, as relative handgrip strength, may be a better tool to capture conceptual concomitant health, which may be a simple, inexpensive, and easy-to-use tool when targeting cardiovascular health in public health level.

Sex Steroids, Sex Hormone-Binding Globulin and Cardiovascular Health in Men and Postmenopausal Women: The Rotterdam Study.

The concept of cardiovascular health was recently introduced. Sex steroids and sex hormone-binding globulin (SHBG) influence different health domains, but no studies assessed their role in cardiovascular health. To assess the association between estradiol (E2), testosterone (T), SHBG, and free androgen index (FAI) with cardiovascular health. Analyses included 1647 men (68.6 y) and 1564 naturally postmenopausal women (69.6 y) with available data on sex steroids and cardiovascular health from the population-based Rotterdam Study. E2, T, SHBG, and FAI. To define cardiovascular health, 7 metrics including 3 health factors (total cholesterol, fasting glucose, and blood pressure) and 4 health behaviors (physical activity, smoking, body mass index, and diet) were adopted. Three category levels of each metric were added up to a total score ranged 0-14. Logistic regression was performed to explore the association between E2, T, SHBG, and FAI and optimal cardiovascular health (OCH) (score of 11-14). OCH was reached by 153 men (9.3%) and 162 women (10.4%). The prevalence of OCH was higher in the lowest tertile of E2 (38.9%), and of T (43.8%), and the highest tertile of SHBG (48.1%) in women, and the highest tertile of T (43.1%) and SHBG (47.1%) in men. After adjustment for confounders, OCH was associated with lower T (odds ratio and 95% confidence interval, 0.69 [0.48-1.00]) and lower FAI (0.43 [0.32-0.57]) and higher levels of SHBG (4.55 [2.99-6.94]) among women and with higher levels of SHBG (2.56 [1.45-4.49]) in men. OCH was associated with sex steroids and with SHBG in both men and women. The complexity and temporality of the interrelation between sex steroids, SHBG, and cardiovascular health requires further investigation.

Tetrahydrobiopterin Concentrations in Normal and Coronary Artery Diseased Heart Tissue

Background: Tetrahydrobiopterin (BH4) is a cofactor that plays a major role in cardiovascular health and disease. BH4 levels in the human heart have not been previously reported. Objective and Methods: Using a novel LC-MS/MS method we measured BH4 and BH2 levels in human heart tissue from subjects with (n=19) and without (n=19) coronary artery disease (CAD). Results: The concentration of BH4 was significantly lower in CAD subjects compared to controls (p=0.0006). There was a trend for a decrease in BH4/BH2 ratio (p=0.09). mRNA expression of GCH1, NOS3 and was not significantly different between CAD and controls. Conclusions: We conclude that the decrease in BH4 concentration in the left ventricular wall of subjects with CAD may be a causative factor or consequence of the failing heart.

Brown adipose tissue: The heat is on the heart.

The study of brown adipose tissue (BAT) has gained significant scientific interest since the discovery of functional BAT in adult humans. The thermogenic properties of BAT are well recognized; however, data generated in the last decade in both rodents and humans reveal therapeutic potential for BAT against metabolic disorders and obesity. Here we review the current literature in light of a potential role for BAT in beneficially mediating cardiovascular health. We focus mainly on BAT's actions in obesity, vascular tone, and glucose and lipid metabolism. Furthermore, we discuss the recently discovered endocrine factors that have a potential beneficial role in cardiovascular health. These BAT-secreted factors may have a favorable effect against cardiovascular risk either through their metabolic role or by directly affecting the heart.

Antiatherogenic effects of ellagic acid and urolithins in vitro

Atherosclerosis, one of the leading causes of death worldwide, is characterized by impaired endothelial function and lipid metabolism, among other factors. Ellagitannins are a class of phenolic compounds that may play a role in cardiovascular health. This work aimed to study the potential atheroprotective effects of urolithins, ellagitannin-derived gut microbiota metabolites, on different key factors in atherosclerosis development: the ability of monocytes to adhere to endothelial cells and the uptake and efflux of cholesterol by macrophages. The biotransformations urolithins undergo in peripheral cells were also evaluated. Results indicated that some urolithins and ellagic acid were able to reduce the adhesion of THP-1 monocytes to human umbilical vein endothelial cells (HUVECs) and the secretion of a cellular adhesion molecule (sVCAM-1) and pro-inflammatory cytokine (IL-6). Urolithin C, a combination of urolithins A and B, and ellagic acid also decreased the accumulation of cholesterol in THP-1-derived macrophages, but they were not able to promote cholesterol efflux. The analysis of cell media by UHPLC-ESI-MSn indicated urolithins and ellagic underwent extensive metabolism, with sulfate and methyl conjugation. This evidence indicates that atherosclerotic processes may be attenuated by urolithins, but future human intervention trials are required to establish if is translated in vivo.

Dietary Nitrate, Nitric Oxide, and Cardiovascular Health

Emerging evidence strongly suggests that dietary nitrate, derived in the diet primarily from vegetables, could contribute to cardiovascular health via effects on nitric oxide (NO) status. NO plays an essential role in cardiovascular health. It is produced via the classical L-arginine–NO-synthase pathway and the recently discovered enterosalivary nitrate–nitrite–NO pathway. The discovery of this alternate pathway has highlighted dietary nitrate as a candidate for the cardioprotective effect of a diet rich in fruit and vegetables. Clinical trials with dietary nitrate have observed improvements in blood pressure, endothelial function, ischemia-reperfusion injury, arterial stiffness, platelet function, and exercise performance with a concomitant augmentation of markers of NO status. While these results are indicative of cardiovascular benefits with dietary nitrate intake, there is still a lingering concern about nitrate in relation to methemoglobinemia, cancer, and cardiovascular disease. It is the purpose of this review to present an overview of NO and its critical role in cardiovascular health; to detail the observed vascular benefits of dietary nitrate intake through effects on NO status as well as to discuss the controversy surrounding the possible toxic effects of nitrate.