Nutrition, Thrombosis, and Cardiovascular Disease

Previous studies reported an inverse association between healthy dietary patterns (such as Mediterranean diet) and the incidence of cardiovascular events. As the mechanism accounting for cardiovascular disease is prevalently due to the atherothrombosis, where a pivotal role is played by platelet activation, it would be arguable that diets with protective effects against cardiovascular disease exert an anti-atherothrombotic effect via inhibition of platelet activation. There are several and sparse typologies of studies, which investigated if single nutrients by diets recognized as having cardiovascular protection may exert an antithrombotic effect. The most investigated nutrients are key components of the Mediterranean diets such as fruits and vegetables, fish, olive oil, and wine; other diets with protective effects include nuts and cocoa. Here we summarize experimental and human interventional studies which investigated the antithrombotic effects of such nutrients in experimental models of thrombosis or analyzed biomarkers of clotting, platelet, and fibrinolysis activation in human; furthermore in vitro studies explored the underlying mechanism at level of several cell lines such as platelets or endothelial cells. In this context, we analyzed if nutrients affect simultaneously or separately clotting, platelet, and fibrinolysis pathways giving special attention to the relationship between oxidative stress and thrombosis as most nutrients are believed to possess antioxidant properties.

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Defibrotide Inhibits Platelet Activation by Cathepsin G Released From Stimulated Polymorphonuclear Leukocytes

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648519 ◽

1992 ◽

Vol 67 (06) ◽

pp. 660-664 ◽

Cited By ~ 17

Author(s):

Virgilio Evangelista ◽

Paola Piccardoni ◽

Giovanni de Gaetano ◽

Chiara Cerletti

Keyword(s):

Platelet Activation ◽

Polymorphonuclear Leukocytes ◽

Direct Interaction ◽

Cathepsin G ◽

In Vivo Test ◽

Cell Functions ◽

Test Models ◽

Antithrombotic Effects

SummaryDefibrotide is a polydeoxyribonucleotide with antithrombotic effects in experimental animal models. Most of the actions of this drug have been observed in in vivo test models but no effects have been reported in in vitro systems. In this paper we demonstrate that defibrotide interferes with polymorphonuclear leukocyte-induced human platelet activation in vitro. This effect was not related to any direct interaction with polymorphonuclear leukocytes or platelets, but was due to the inhibition of cathepsin G, the main biochemical mediator of this cell-cell cooperation. Since cathepsin G not only induces platelet activation but also affects some endothelial cell functions, the anticathepsin G activity of defibrotide could help to explain the antithrombotic effect of this drug.

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Reno-protective mechanisms of epoxyeicosatrienoic acids in cardiovascular disease

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00606.2011 ◽

2012 ◽

Vol 302 (3) ◽

pp. R321-R330 ◽

Cited By ~ 23

Author(s):

Ahmed A. Elmarakby

Keyword(s):

Blood Pressure ◽

Cardiovascular Disease ◽

Animal Models ◽

Vascular Function ◽

Organ Damage ◽

Reduce Blood Pressure ◽

Experimental Models ◽

Epoxyeicosatrienoic Acids ◽

Protective Effects ◽

Protective Mechanisms

Cardiovascular disease (CVD) is the leading cause of mortality worldwide, and it is well known that end-stage renal disease (ESRD) is a profound consequence of the progression of CVD. Present treatments only slow CVD progression to ESRD, and it is imperative that new therapeutic strategies are developed to prevent the incidence of ESRD. Because epoxyeicosatrienoic acids (EETs) have been shown to elicit reno-protective effects in hypertensive animal models, the current review will focus on addressing the reno-protective mechanisms of EETs in CVD. The cytochrome P-450 epoxygenase catalyzes the oxidation of arachidonic acid to EETs. EETs have been identified as endothelium-derived hyperpolarizing factors (EDHFs) with vasodilatory, anti-inflammatory, antihypertensive, and antiplatelet aggregation properties. EETs also have profound effects on vascular migration and proliferation and promote angiogenesis. The progression of CVD has been linked to decreased EETs levels, leading to the concept that EETs should be therapeutically targeted to prevent end-organ damage associated with CVD. However, EETs are quickly degraded by the enzyme soluble epoxide hydrolase (sEH) to their less active diols, dihydroxyeicosatrienoic acids (DHETs). As such, one way to increase EETs level is to inhibit their degradation to DHETs by using sEH inhibitors. Inhibition of sEH has been shown to effectively reduce blood pressure and organ damage in experimental models of CVD. Another approach to target EETs is to develop EET analogs with improved solubility and resistance to auto-oxidation and metabolism by sEH. For example, stable ether EET analogs dilate afferent arterioles and lower blood pressure in hypertensive rodent animal models. EET agonists also improve insulin signaling and vascular function in animal models of metabolic syndrome.

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Abstract P254: Risk Factors For Venous Thromboembolism in a Cohort of French Women

Circulation ◽

10.1161/circ.125.suppl_10.ap254 ◽

2012 ◽

Vol 125 (suppl_10) ◽

Author(s):

Martin Lajous ◽

Laura Tondeur ◽

Agnes Fournier ◽

Francoise Clavel-Chapelon

Keyword(s):

Physical Activity ◽

Risk Factors ◽

Cardiovascular Disease ◽

Venous Thromboembolism ◽

Fruits And Vegetables ◽

Smoking Status ◽

Premenopausal Women ◽

Prior History ◽

Inverse Association ◽

Vein Thrombosis

Background: There is controversy over whether cardiovascular disease and venous thromboembolism (VTE) share risk factors. Prospective information on risk factors for VTE in otherwise healthy individuals is limited. Methods and Results We evaluated the relation between known risk factors for cardiovascular disease and incidence of VTE among 65,272 French women in the E3N prospective cohort study with no prior history of VTE and who were free of cardiovascular disease or cancer in 1993. All information was self-reported via mailed questionnaires and diet and physical activity were assessed using previously validated instruments. Between 1993 and 2007, 766 cases of deep vein thrombosis or pulmonary embolism were first identified through self-reports and validated using medical records and information from treating physicians. Cases were considered valid if the diagnosis was based on an imaging procedure. We evaluated the following risk factors: education, menopause, postmenopausal hormone use, treated hypercholesterolemia and hypertension, diabetes, body mass index (BMI), physical activity, smoking status and intake of alcohol, red meat, fish, fruits and vegetables, fiber and coffee. In a multivariable model with age as the time scale, we found that, compared to women with a BMI <22 kg/m2, the HR (95%CI) was 1.35 (1.14, 1.60) for 22–24.9 kg/m2, 2.11 (1.73, 2.57) for 25–29.9 kg/m2 and 2.88 (2.08, 3.98) for ≥30 kg/m2 and the p-trend was <0.0001. Menopause was found to be inversely associated with VTE risk [HR=0.60 (95%CI 0.45–0.80); postmenopausal vs. premenopausal women]. In analyses restricted to postmenopausal women, relative to never users current use of postmenopausal hormones was significantly associated to VTE risk [HR=1.44 (95%CI 1.18–1.74)]. No significant association was found with dietary and other cardiovascular risk factors. Conclusion In this large prospective study only some risk factors for cardiovascular disease were associated to VTE incidence. We observed a strong inverse association between menopause and VTE.

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Methylprednisolone Protects SAP and Pancreatitis-Associated ALI in Mice by Inhibiting NLRP3 Inflammasome Through NF-κB

10.21203/rs.3.rs-96231/v1 ◽

2020 ◽

Author(s):

Chuan-jiang Liu ◽

Qiang Fu ◽

Wenjing Zhou ◽

Xu Zhang ◽

Rui Chen ◽

...

Keyword(s):

Lung Tissue ◽

Nlrp3 Inflammasome ◽

Antioxidant Properties ◽

Underlying Mechanism ◽

Peritoneal Macrophages ◽

Dependent Manner ◽

Expression Levels ◽

Tnf Α

Abstract Background: Methylprednisolone (MP) is a synthetic corticosteroid with potent anti-inflammatory and antioxidant properties used as therapy for a variety of diseases. The underlying mechanism of MP to reduce acute pancreatitis still needs to be elucidated.Methods: Twenty-four male C57BL/6 mice (6-8 weeks) were used to establish SAP mouse model by administering an intraperitoneal injection of Cae and LPS. Amylase expression levels of serum and PLF were measured with an amylase assay kit. The concentrations of IL-1β and TNF-α in the serum and PLF were detected by ELISA. The level of pancreatic and lung tissue damage and inflammation was assessed by H&E staining and immunofluorescence staining. Western blot and qPCR were used to detect the expression levels of NLRP3, IL-1β and TNF-αin vivo and in vitro.Results: In this study, we found MP, used in the early phase of SAP, decreased the levels of IL-1β and TNF-α in serum and peritoneal lavage fluids (PLF), reduced the level of serum amylase and the expression of MPO in lung tissue, attenuated the pathological injury of the pancreas and lungs in a dose-dependent manner. The expression of NLRP3 and IL-1β in pancreas and lungs was down-regulated significantly depending on the MP concentration. In vitro, MP reduced the levels of IL-1β and TNF-α by down-regulating the expression of NLRP3, IL-1β and p-NF-κB in isolated peritoneal macrophages. Conclusion: MP can attenuate the injury of pancreas and lungs, and the inflammatory response in SAP mice by down-regulating the activation of NF-κB and the NLRP3 inflammasome.

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Abstract P116: The Impact of Diet Low in Fruits and Vegetables on Cardiovascular Disease Burden Across 195 Countries in 2015

Circulation ◽

10.1161/circ.135.suppl_1.p116 ◽

2017 ◽

Vol 135 (suppl_1) ◽

Author(s):

Patrick J Sur ◽

Ashkan Afshin

Keyword(s):

Cardiovascular Disease ◽

Fruits And Vegetables ◽

Population Level ◽

Optimal Level ◽

Protective Effects ◽

Disability Adjusted Life Years ◽

Country Level ◽

Disability Adjusted Life ◽

Life Years ◽

The Impact

Introduction: While cardio-protective effects of fruits and vegetables are well-established, the impact of their suboptimal intake on the CVD burden across nations and levels of development has not been evaluated. Objective: To systematically quantify the burden of CVD attributable to low intake of fruits and low intake of vegetables in 195 countries by age, sex, country, and development status in 2015. Methods: We obtained data on consumption of fruits and vegetables from nationally or subnationally representative nutrition surveys and data on their national availability from the UN FAO. Etiologic effect sizes of fruits and vegetables on CVD endpoints were obtained from meta- analyses of prospective cohort studies. The optimal level of intakes for each was determined based on the levels associated with lowest risk of mortality in prospective observational studies. A comparative risk assessment analysis was conducted to quantify the proportion of disability- adjusted life years (DALYs) attributable to low intake of each. The variation of this burden was further evaluated across different levels of our newly developed socio-demographic index (SDI). Results: In 2015, low intake of fruits accounted for 57.3 (95% UI: 37.1- 78.4) million DALYs due to CVD globally (41.5% from IHD and 58.5% from stroke). Low intake of vegetable caused 44.6 (23.6- 68.8) million CVD DALYs (67.3% IHD and 32.7% stroke). The highest burden of CVD attributable to low intake of fruits and vegetables was seen in the middle and low-middle SDI quintiles (17.2 and 14.3% of total DALYs), while the lowest burden for each was seen in high and high-middle SDI quintiles (12.7 and 11.2%). At the country level, the attributable CVD burden ranged from 5.1% of total DALYs (Rwanda) to 23.2% (Bangladesh) for low intake of fruit and from 5.9% (North Korea) to 19.4% (Mongolia) for low intake of vegetable. Conclusion: Our findings suggest that population inventions to increase consumption of fruits and vegetables at population level could save millions of life years globally. Figure. Age-standardized proportion of disability-adjusted life years attributable to low intake of fruits (A) and vegetables (B) from cardiovascular disease among adults (> 25y) in 2015.

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Inhibitory effects of astaxanthin on postovulatory porcine oocyte aging in vitro

Scientific Reports ◽

10.1038/s41598-020-77359-6 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Bao-Yu Jia ◽

De-Cai Xiang ◽

Qing-Yong Shao ◽

Bin Zhang ◽

Shao-Na Liu ◽

...

Keyword(s):

Antioxidant Properties ◽

Underlying Mechanism ◽

Oocyte Quality ◽

Beneficial Effects ◽

Oocyte Aging ◽

Reagent Treatment ◽

Porcine Oocyte ◽

Antioxidant Gene Expression ◽

Actin Expression

AbstractMammalian oocytes represent impaired quality after undergoing a process of postovulatory aging, which can be alleviated through various effective ways such as reagent treatment. Accumulating evidences have revealed the beneficial effects of astaxanthin (Ax) as a potential antioxidant on reproductive biology. Here, porcine matured oocytes were used as a model to explore whether Ax supplement can protect against oocyte aging in vitro and the underlying mechanism, and therefore they were cultured with or without 2.5 μM Ax for an additional 24 h. Aged oocytes treated with Ax showed improved yield and quality of blastocysts as well as recovered expression of maternal genes. Importantly, oxidative stress in aged oocytes was relieved through Ax treatment, based on reduced reactive oxygen species and enhanced glutathione and antioxidant gene expression. Moreover, inhibition in apoptosis and autophagy of aged oocyte by Ax was confirmed through decreased caspase-3, cathepsin B and autophagic activities. Ax could also maintain spindle organization and actin expression, and rescue functional status of organelles including mitochondria, endoplasmic reticulum, Golgi apparatus and lysosomes according to restored fluorescence intensity. In conclusion, Ax might provide an alternative for ameliorating the oocyte quality following aging in vitro, through the mechanisms mediated by its antioxidant properties.

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Flavonoids and Colorectal Cancer Prevention

Antioxidants ◽

10.3390/antiox7120187 ◽

2018 ◽

Vol 7 (12) ◽

pp. 187 ◽

Cited By ~ 17

Author(s):

Yanyan Li ◽

Tao Zhang ◽

Grace Chen

Keyword(s):

Colorectal Cancer ◽

Fruits And Vegetables ◽

Cellular Proliferation ◽

Vegetable Consumption ◽

Inverse Association ◽

Protective Effects ◽

Colon Tumorigenesis ◽

Common Cancer ◽

Colorectal Cancer Prevention ◽

Related Mortality

Colorectal cancer (CRC) is the third most common cancer, but despite advances in treatment, it remains the second most common cause of cancer-related mortality. Prevention may, therefore, be a key strategy in reducing colorectal cancer deaths. Given reports of an inverse association between fruit and vegetable consumption with colorectal cancer risk, there has been significant interest in understanding the metabolism and bioactivity of flavonoids, which are highly abundant in fruits and vegetables and account for their pigmentation. In this review, we discuss host and microbiota-mediated metabolism of flavonoids and the potential mechanisms by which flavonoids can exert protective effects against colon tumorigenesis, including regulation of signaling pathways involved in apoptosis, cellular proliferation, and inflammation and modulation of the gut microbiome.

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Plant polyphenols in cancer and heart disease: implications as nutritional antioxidants

Nutrition Research Reviews ◽

10.1079/095442200108729016 ◽

2000 ◽

Vol 13 (1) ◽

pp. 79-106 ◽

Cited By ~ 419

Author(s):

Garry G. Duthie ◽

Susan J. Duthie ◽

Janet A. M. Kyle

Keyword(s):

Antioxidant Activity ◽

Heart Disease ◽

Mammalian Cells ◽

Fruits And Vegetables ◽

Phenylpropanoid Pathway ◽

Protective Effects ◽

Dietary Intakes ◽

Intracellular Location ◽

Processing And Storage

AbstractCertain dietary antioxidants such as vitamin E and vitamin C are important for maintaining optimum health. There is now much interest in polyphenolic products of the plant phenylpropanoid pathway as they have considerable antioxidant activityin vitroand are ubiquitous in our diet. Rich sources include tea, wine, fruits and vegetables although levels are affected by species, light, degree of ripeness, processing and storage. This confounds the formulation of databases for the estimation of dietary intakes. Most attention to date has focused on the flavonoids, a generic term which includes chalcones, flavones, flavanones, flavanols and anthocyanins. There is little convincing epidemiological evidence that intakes of polyphenols are inversely related to the incidence of cancer whereas a number of studies suggest that high intakes of flavonoids may be protective against CHD. In contrast, numerous cell culture and animal models indicate potent anticarcinogenic activity by certain polyphenols mediated through a range of mechanisms including antioxidant activity, enzyme modulation, gene expression, apoptosis, upregulation of gap junction communication and P-glycoprotein activation. Possible protective effects against heart disease may be due to the ability of some polyphenols to prevent the oxidation of LDL to an atherogenic form although anti-platelet aggregation activity and vasodilatory properties are also reported. However, some polyphenols are toxic in mammalian cells. Thus, until more is known about their bioavailability, metabolism and intracellular location, increasing intakes of polyphenols by supplements or food fortification may be unwise.

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Progressive Increase in Platelet Activation With Smoke Exposure: Human Subject and In-Vitro Studies

ASME 2007 Summer Bioengineering Conference ◽

10.1115/sbc2007-176018 ◽

2007 ◽

Author(s):

Gaurav Girdhar ◽

Sulan Xu ◽

Jolyon Jesty ◽

Danny Bluestein

Keyword(s):

Cigarette Smoke ◽

Platelet Activation ◽

Human Subject ◽

Prolonged Exposure ◽

Human Subjects ◽

Progressive Increase ◽

In Vitro Studies ◽

Protective Effects ◽

Shs Exposure

Second hand cigarette smoke (SHS) is one of the major risk factors for cardiovascular disease (CVD) and has been shown to substantiate platelet activation and aggregation in several studies [1, 2]. Most of these studies, under chronic or acute exposure conditions or over prolonged exposure, do not represent the initiation of a disease state or hematological damage under normal levels of cigarette smoke. These above studies of platelet activation with SHS together with our previous in-vitro studies demonstrating cardio-protective effects of nicotine [3], have motivated the present investigation of physiological levels of SHS exposure on human subjects and within an in-vitro endothelial cell-platelet system, with cigarettes (or smoke extracts) of varying nicotine content to confirm analogous cardio-protective effects of nicotine.

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Metabolic Profiling of Buddleia indica Leaves using LC/MS and Evidence of their Antioxidant and Hepatoprotective Activity Using Different In Vitro and In Vivo Experimental Models

Antioxidants ◽

10.3390/antiox8090412 ◽

2019 ◽

Vol 8 (9) ◽

pp. 412

Author(s):

Fadia S. Youssef ◽

Mohamed L. Ashour ◽

Hesham A. El-Beshbishy ◽

Abdel Nasser B. Singab ◽

Michael Wink

Keyword(s):

Antioxidant Properties ◽

Lipid Peroxide ◽

Hepatoprotective Activity ◽

Experimental Models ◽

Ionization Mass ◽

Necrosis Factor Alpha ◽

Stress Markers ◽

Tnf Α

LC-ESI-MS (Liquid Chromatography coupled with Electrospray Ionization Mass Spectrometry profiling of a methanol extract from Buddleia indica (BIM) leaves revealed 12 main peaks in which verbascoside and buddlenoid B represent the major compounds. The antioxidant and hepatoprotective activities of BIM were investigated using different in vitro and in vivo experimental models. BIM exhibited substantial in vitro antioxidant properties in DPPH· and HepG2 assays. Regarding CCl4 (carbon tetrachloride) induced hepatotoxicity in a rat model, oxidative stress markers became significantly ameliorated after oral administration of BIM. Lipid peroxide levels showed a 51.85% decline relative to CCl4-treated rats. Super oxide dismutase (SOD), total antioxidant status (TAS), and catalase (CAT) revealed a marked increase by 132.48%, 187.18%, and 114.94% relative to the CCl4 group. In a tamoxifen-induced hepatotoxicity model, BIM showed a considerable alleviation in liver stress markers manifested by a 46.06% and 40% decline in ALT (Alanine Transaminase) and AST (Aspartate Transaminase) respectively. Thiobarbituric acid reactive substances (TBARS) were reduced by 28.57% and the tumor necrosis factor alpha (TNF-α) level by 50%. A virtual screening of major secondary metabolites of BIM to TNF-alpha employing the C-docker protocol showed that gmelinoside H caused the most potent TNF- α inhibition as indicated from their high fitting scores. Thus, BIM exhibited a potent hepatoprotective activity owing to its richness in antioxidant metabolites.

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