Release of membrane vesicles, a process conserved in both prokaryotes and eukaryotes, represents an evolutionary link, and suggests essential functions of a dynamic extracellular vesicular compartment (including exosomes, microparticles or microvesicles and apoptotic bodies). Compelling evidence supports the significance of this compartment in a broad range of physiological and pathological processes. However, classification of membrane vesicles, protocols of their isolation and detection, molecular details of vesicular release, clearance and biological functions are still under intense investigation. Here, we give a comprehensive overview of extracellular vesicles. After discussing the technical pitfalls and potential artifacts of the rapidly emerging field, we compare results from meta-analyses of published proteomic studies on membrane vesicles. We also summarize clinical implications of membrane vesicles. Lessons from this compartment challenge current paradigms concerning the mechanisms of intercellular communication and immune regulation. Furthermore, its clinical implementation may open new perspectives in translational medicine both in diagnostics and therapy.

/pdf/membrane-vesicles-current-state-of-the-art-emerging-role-of-2orxx28bfa.pdf

Membrane vesicles, current state-of-the-art: emerging role of extracellular vesicles

Obesity and the risk of heart failure

Obesity adversely affects cardiac function, increases the risk factors for coronary heart disease, and is an independent risk factor for cardiovascular disease. The risk of developing coronary heart disease is directly related to the concomitant burden of obesity-related risk factors. Modest weight loss can improve diastolic function and affect the entire cluster of coronary heart disease risk factors simultaneously. This statement from the American Heart Association Council on Nutrition, Physical Activity, and Metabolism reviews the relationship between obesity and the cardiovascular system, evaluates the effect of weight loss on coronary heart disease risk factors and coronary heart disease, and provides practical weight management treatment guidelines for cardiovascular healthcare professionals. The data demonstrate that weight loss and physical activity can prevent and treat obesity-related coronary heart disease risk factors and should be considered a primary therapy for obese patients with cardiovascular disease.

/pdf/clinical-implications-of-obesity-with-specific-focus-on-55atg36cly.pdf

Clinical Implications of Obesity With Specific Focus on Cardiovascular Disease A Statement for Professionals From the American Heart Association Council on Nutrition, Physical Activity, and Metabolism: Endorsed by the American College of Cardiology Foundation

Endothelial microparticles (EMP) are complex vesicular structures shed from activated or apoptotic endothelial cells. They play a remarkable role in coagulation, inflammation, endothelial function, and angiogenesis and thus disturb the vascular homeostasis, contributing to the progression of vascular diseases. As a cause or a consequence, elevated levels of EMP were found in plasma from patients with vascular diseases, where they serve as a surrogate marker of endothelial function. More recent data challenged the presumed deleterious role of EMP because they could promote cell survival, exert antiinflammatory effects, counteract coagulation processes, or induce endothelial regeneration. This review focuses on the ambivalent role of EMP in vascular homeostasis.

The Many Faces of Endothelial Microparticles

Collectively, cardiovascular disease (including stroke), cancer, and diabetes account for approximately two thirds of all deaths in the United States and about 700 billion dollars in direct and indirect economic costs each year. Current approaches to health promotion and prevention of cardiovascular disease, cancer, and diabetes do not approach the potential of the existing state of knowledge. A concerted effort to increase application of public health and clinical interventions of known efficacy to reduce prevalence of tobacco use, poor diet, and insufficient physical activity-the major risk factors for these diseases-and to increase utilization of screening tests for their early detection could substantially reduce the human and economic cost of these diseases. In this article, the ACS, ADA, and AHA review strategies for the prevention and early detection of cancer, cardiovascular disease, and diabetes, as the beginning of a new collaboration among the three organizations. The goal of this joint venture is to stimulate substantial improvements in primary prevention and early detection through collaboration between key organizations, greater public awareness about healthy lifestyles, legislative action that results in more funding for and access to primary prevention programs and research, and reconsideration of the concept of the periodic medical checkup as an effective platform for prevention, early detection, and treatment.

Preventing Cancer, Cardiovascular Disease, and Diabetes. A Common Agenda for the American Cancer Society, the American Diabetes Association, and the American Heart Association

Context: Cell-derived microparticles are supposed to be involved in atherogenesis. Objective: This study aimed to evaluate circulating microparticles in obese women and their relation with anthropometric measures and endothelial dysfunction. Design, Setting, and Participants: Forty-one obese [body mass index (BMI) > 30 kg/m2] women and 40 normal weight (BMI < 25 kg/m2) age-matched women were studied. Flow cytometry was used to assess microparticles by quantification of circulating endothelial microparticles (EMP, CD31+/CD42b−) and platelet microparticles (PMP, CD31+/CD42b+) in peripheral blood; endothelium-dependent flow-mediated vasodilation (FMD) was evaluated in the right brachial artery after reactive hyperemia. Results: Compared with lean women, obese women presented significantly higher numbers of EMP and PMP, and reduced FMD. BMI did not correlate with either EMP (r = 0.02, P = 0.9) or PMP (r = −0.07, P = 0.645), whereas waist-to-hip ratio (WHR) showed significant correlation with both microparticl...

/pdf/endothelial-microparticles-correlate-with-endothelial-67w2hereec.pdf

Endothelial Microparticles Correlate with Endothelial Dysfunction in Obese Women

BRIEF REPORT Endothelial Microparticles Correlate with Endothelial Dysfunction in Obese Women

Context: Two-hour postprandial hyperglycemia is related to chronic complications of diabetes and is currently used in the international guidelines to drive the therapy. Objective: Our objective was to assess the size and timing of post-meal glucose peaks in the everyday life of type 2 diabetic patients and the relationship with carotid atherosclerosis. Design, Setting, and Patients: This was an observational study performed in 644 outpatients with type 2 diabetes attending diabetes clinics located in the area of the Campania County, South Italy, who provided complete home blood glucose profiles and centralized carotid intima-media thickness (CIMT) assessment. The study was conducted from 2001–2005. Main Outcome Measures: Incremental glucose peak (IGP) was the maximal incremental increase in blood glucose obtained at any point after the meal. CIMT was assessed by carotid sonography. Results: The level of glycosylated hemoglobin and CIMT progressively increased across quintiles of IGP (P for trend = 0.01 fo...

/pdf/post-meal-glucose-peaks-at-home-associate-with-carotid-3lzgcnq87e.pdf

Post-meal glucose peaks at home associate with carotid intima-media thickness in type 2 diabetes.

OBJECTIVE —Obesity is an important risk factor for heart failure in both women and men. Dyssynchrony between right and left ventricular contraction and relaxation has been identified as an independent predictor of heart failure. We examined the relationship of ventricular synchronization abnormalities with the concentration of proinflammatory cytokines in obese women at baseline and after sustained weight loss. RESEARCH DESIGN AND METHODS —Echocardiographic parameters of ventricular dyssynchrony, circulating levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-18, and C-reactive protein (CRP) were investigated in 67 healthy, premenopausal obese women and 40 age-matched normal-weight women. RESULTS —Compared with nonobese women, obese women had increased concentrations of CRP ( P P P P P P P P P P CONCLUSIONS —In obese women, ventricular dyssynchrony correlates with body fat, possibly through inappropriate secretion of cytokines. Weight loss represents a safe method for downregulating the inflammatory state and ameliorating cardiac function in obese women.

https://care.diabetesjournals.org/content/diacare/27/1/47.full.pdf

Effect of Weight Loss on Cardiac Synchronization and Proinflammatory Cytokines in Premenopausal Obese Women

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Endothelial Microparticles Correlate with Endothelial Dysfunction in Obese Women

BRIEF REPORT Endothelial Microparticles Correlate with Endothelial Dysfunction in Obese Women

Post-meal glucose peaks at home associate with carotid intima-media thickness in type 2 diabetes.

Effect of Weight Loss on Cardiac Synchronization and Proinflammatory Cytokines in Premenopausal Obese Women