Platelets, Obesity, and the Metabolic Syndrome

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. SCI-34-SCI-34
Author(s):  
Jane Freedman
Keyword(s):  
Gene Expression ◽  
Cardiovascular Disease ◽  
Platelet Function ◽  
Conflicts Of Interest ◽  
Innate Immune ◽  
Metabolic Dysfunction ◽  
Reverse Transcription Pcr ◽  
The Metabolic Syndrome ◽  
Excess Adiposity ◽  
All Cause Mortality

Abstract Abstract SCI-34 Cardiovascular disease continues to be the major cause of morbidity and mortality in North America and a growing problem in many other parts of the world. The risk of premature atherosclerosis and cardiovascular events rises with increasing obesity and excess adiposity has been linked to increased all-cause mortality. Current estimates show that one in four ischemic heart disease events are attributable to excess weight. Inflammation of adipose tissue orchestrated by monocyte/macrophage infiltration and overproduction of proinflammatory and proatherogenic cytokines may mediate metabolic dysfunction and vascular disease in human obesity. Importantly, obesity has been associated with increased cardiovascular disease as well as enhanced platelet function and thrombosis. We recently measured expression of 48 genes by high-throughput quantitative reverse transcription PCR (qRT-PCR) in over 2250 participants of the Framingham Offspring and Omni minority cohorts (FHS) using RNA from isolated platelets and found that specific inflammatory transcripts including ICAM1, IL1R, IFNG, IL6, COX2, TNF, TLR2, and TLR4 were significantly and positively associated with higher body mass index (BMI) by regression analysis. With the additional measurement of 196 genes, the data has remained extraordinarily consistent. Other cardiovascular risk factors rarely associate with platelet gene expression and BMI remains specifically associated with inflammatory transcripts related to the NFkB-innate immune and inflammatory pathways. These surprising data led to the question: Why would the anucleate platelet have gene expression changes specifically in the setting of increased BMI and can this powerful clinical association be explored using both pre-clinical and clinical studies to find new targets for disease and define new mechanisms for platelet function beyond thrombosis? Disclosures: No relevant conflicts of interest to declare.

scholarly journals Modulation of the Bovine Trophoblastic Innate Immune Response by Brucella abortus

2008 ◽  
Vol 76 (5) ◽  
pp. 1897-1907 ◽  
Author(s):  
Alcina V. Carvalho Neta ◽  
Ana P. R. Stynen ◽  
Tatiane A. Paixão ◽  
Karina L. Miranda ◽  
Fabiana L. Silva ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Innate Immune Response ◽  
Brucella Abortus ◽  
Innate Immune ◽  
Chemokine Expression ◽  
Trophoblastic Cells ◽  
Proinflammatory Mediators ◽  
Reverse Transcription Pcr ◽  
Cytokines And Chemokines

ABSTRACT Brucellosis is still a widespread zoonotic disease. Very little is known about the interaction between Brucella abortus and trophoblastic cells, which is essential for better understanding the pathogenesis of the Brucella-induced placentitis and abortion, a key event for transmission of the disease. The goal of this study was to evaluate the profile of gene expression by bovine trophoblastic cells during infection with B. abortus. Explants of chorioallantoic membranes were inoculated with B. abortus strain 2308. Microarray analysis was performed at 4 h after infection, and expression of cytokines and chemokines by trophoblastic cells was assessed by real-time reverse transcription-PCR at 6 and 12 h after inoculation. In addition, cytokine and chemokine expression in placentomes from experimentally infected cows was evaluated. Expression of proinflammatory genes by trophoblastic cells was suppressed at 4 h after inoculation, whereas a significant upregulation of CXC chemokines, namely, CXCL6 (GCP-2) and CXCL8 (interleukin 8), was observed at 12 but not at 6 h after inoculation. Placentomes of experimentally infected cows had a similar profile of chemokine expression, with upregulation of CXCL6 and CXCL8. Our data indicate that B. abortus modulates the innate immune response by trophoblastic cells, suppressing the expression of proinflammatory mediators during the early stages of infection that is followed by a delayed and mild expression of proinflammatory chemokines, which is similar to the profile of chemokine expression in the placentomes of experimentally infected cows. This trophoblastic response is likely to contribute to the pathogenesis of B. abortus-induced placentitis.

scholarly journals Chronic activation of the innate immune system may underlie the metabolic syndrome

2001 ◽  
Vol 119 (3) ◽  
pp. 122-127 ◽  
Author(s):  
Bruce Bartholow Duncan ◽  
Maria Inês Schmidt
Keyword(s):  
Diabetes Mellitus ◽  
Cardiovascular Disease ◽  
Metabolic Syndrome ◽  
Immune System ◽  
Innate Immune System ◽  
Innate Immune ◽  
Cross Sectional ◽  
Markers Of Inflammation ◽  
The Metabolic Syndrome ◽  
Chronic Activation

CONTEXTO: The metabolic syndrome is characterized by a clustering, in free-living populations, of cardiovascular and diabetes risk factors generally linked to insulin resistance, obesity and central obesity. Consonant with the well-established inflammatory pathogenesis of atherosclerotic disease, the metabolic syndrome is now being investigated in relation to its inflammatory nature. OBJETIVO: We present cross-sectional findings demonstrating that markers of inflammation correlate with components of the metabolic syndrome, and prospective findings of the ARIC Study indicating that markers of inflammation and endothelial dysfunction predict the development of diabetes mellitus and weight gain in adults. We present biological evidence to suggest that chronic activation of the innate immune system may underlie the metabolic syndrome, characterizing the common soil for the causality of type 2 diabetes mellitus and cardiovascular disease. CONCLUSIONS: Better understanding of the role of the innate immune system in these diseases may lead to important advances in the prediction and management of diabetes and cardiovascular disease.

Physical activity, fitness and cardiovascular disease risk in adults: interactions with insulin resistance and obesity

2006 ◽  
Vol 110 (4) ◽  
pp. 409-425 ◽  
Author(s):  
Jason M. R. Gill ◽  
Dalia Malkova
Keyword(s):  
Physical Activity ◽  
Cardiovascular Disease ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Normal Weight ◽  
Metabolic Dysfunction ◽  
Cvd Risk ◽  
Insulin Resistant ◽  
The Metabolic Syndrome ◽  
High Level

There is a considerable body of evidence gathered from studies over the past half a century indicating that a high level of physical activity and a moderately high or high degree of cardiorespiratory fitness reduces the risk of CVD (cardiovascular disease). Recent data suggest that high levels of physical activity or fitness may be particularly beneficial to individuals with insulin-resistant conditions, such as the metabolic syndrome, Type II diabetes or obesity. These individuals, if unfit and sedentary, exhibit increased CVD risk, but their dose–response relationship for physical activity/fitness appears to be particularly steep such that, when they undertake high levels of activity (or have high fitness), their level of risk becomes closer to that of their normal weight or nondiabetic peers. This may be due to effects of physical activity in normalizing the metabolic dysfunction particularly associated with insulin-resistant conditions.

A Meta-Analysis of Randomized Controlled Trials of Aspirin in Primary Prevention of Cardiovascular Disease.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 174-174
Author(s):  
Nina C Raju ◽  
Magda Sobieraj-Teague ◽  
John W Eikelboom
Keyword(s):  
Myocardial Infarction ◽  
Cardiovascular Disease ◽  
Primary Prevention ◽  
Cardiovascular Mortality ◽  
Cardiovascular Events ◽  
Conflicts Of Interest ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Controlled Trials ◽  
All Cause Mortality

Abstract Abstract 174 Primary prevention with aspirin reduces the risk of non-fatal cardiovascular events but has not been demonstrated to reduce mortality. We performed an updated meta-analysis of randomised controlled trials of aspirin in primary prevention to obtain best estimates of the benefits and harm of aspirin compared with no aspirin with a focus on mortality. Eligible articles were identified by computerized search of MEDLINE, EMBASE, Cochrane library and CINAHL databases, review of bibliographies of relevant publications and a related article search using PubMed. The outcomes of interest included all cause mortality, cardiovascular mortality, the composite of myocardial infarction, stroke or death, and bleeding. 2 reviewers independently extracted study information and data. Data were pooled from individual trials using the DerSimonian-Laird random-effects model and results are presented as relative risk (RR) and 95% confidence intervals (CI). 8 studies comprising a total of 96,726 subjects were included. Aspirin reduced all-cause mortality (RR 0.94; 95%CI 0.88–1.00), the composite of myocardial infarction, stroke or cardiovascular death (RR 0.87; 95%CI 0.82–0.93), and myocardial infarction (RR 0.8; 95%CI 0.66–0.98) but did not significantly reduce cardiovascular mortality (RR 0.94; 95%CI 0.82–1.08) or stroke (RR 0.93; 95%CI 0.81–1.07). Aspirin increased the risk of major bleeding (RR; 1.69 95%CI 1.38–2.08), gastrointestinal bleeding (RR 1.38; 95%CI 1.16–1.65) and hemorrhagic stroke (RR 1.36; 95%CI 1.01–1.84). There was no interaction between subjects with or without diabetes for the outcomes of all cause mortality, cardiovascular mortality, the composite of myocardial infarction, stroke or death. Aspirin therapy in subjects with no prior history of cardiovascular disease reduces the risk of cardiovascular events, myocardial infarction and overall mortality. These benefits are achieved at the expense of increased bleeding. Disclosures: No relevant conflicts of interest to declare.

Cardiovascular Risk Assessement in Osteoporotic Patients Using Osteoprotegerin as a Reliable Predictive Biochemical Marker

2018 ◽  
pp. 253
Author(s):  
Noora Wael Rasheed ◽  
Ooroba Jameel Taresh
Keyword(s):  
Cardiovascular Disease ◽  
Metabolic Syndrome ◽  
Cardiovascular Risk ◽  
Serum Level ◽  
Biochemical Markers ◽  
Hdl Cholesterol ◽  
Predictive Marker ◽  
Serum Levels ◽  
Arterial Calcification ◽  
The Metabolic Syndrome

       Some studies indicated a relationship between increased serum levels of osteoprotegerin with arterial calcification and as a result, it leads to the risk of cardiovascular disease. In our study group we selected patients with osteoporosis, with similar age and body mass index for the assessment of the relationship between cardiovascular disease and osteoprotegerin serum level. We took into account the analysis of correlation and association between the presence of distinct patterns of atherosclerosis and associated diseases like high blood pressure,  diabetes mellitus, low HDL cholesterol, increased LDL cholesterol, increased triglycerides and was the case of presence of any type of dyslipidemia, in case of pre-existent treatment. Objective of study was the assessment of osteoprotegerin value as predictive marker for cardiovascular and metabolic risk in osteoporotic patients. Our results showed significant correlations of parathyroid hormone, osteocalcin and biochemical markers of bone with glucose metabolism and lipid were found in our research, maintaining crosstalk between calcium and biochemical markers of bone and cardiovascular risk. The serum level of Osteoprotegerin has been shown to have a large predictive value for the metabolic syndrome as a cardiovascular risk standard in patients with osteoporosis. The osteoprotegerin serum levels were increased in the patients with metabolic syndrome as a protective response facing the atherosclerotic lesions.

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