40,248 research outputs found
Increased endothelin-1-mediated vasoconstrictor tone in human obesity: effects of gut hormones
No full textThe heavy impact of obesity on the development and progression of cardiovascular disease has sparked sustained efforts to uncover the mechanisms linking excess adiposity to vascular dysfunction. Impaired vasodilator reactivity has been recognized as an early hemodynamic abnormality in obese patients, but also increased vasoconstrictor tone importantly contributes to their vascular damage. In particular, upregulation of the endothelin (ET)-1 system, consistently reported in these patients, might accelerate atherosclerosis and its complication, given the pro-inflammatory and mitogenic properties of ET-1. In recent years, a number of gut hormones, in addition to their role as modulators of food intake, energy balance, glucose and lipid metabolism, and insulin secretion and action, have demonstrated favorable vascular actions. They increase the bioavailability of vasodilator mediators like nitric oxide, but they have also been shown to inhibit the ET-1 system. These features make gut hormones promising tools for targeting both the metabolic and cardiovascular complications of obesity, a view supported by recent large-scale clinical trials indicating that novel drugs for type 2 diabetes with cardiovascular potential may translate into clinically significant advantages. Therefore, there is real hope that better understanding of the properties of gut-derived substances might provide more effective therapies for the obesity-related cardiometabolic syndrome
Vascular hyperpolarization in human physiology and cardiovascular risk conditions and disease
No full textHyperpolarization causing smooth muscle relaxation contributes to the maintenance of vascular homeostasis, particularly in small-calibre arteries and arterioles. It may also become a compensatory vasodilator mechanism upregulated in states with impaired nitric oxide (NO) availability. Bioassay of vascular hyperpolarization in the human circulation has been hampered by the complexity of mechanisms involved and the limited availability of investigational tools. Firm evidence, however, supports the notion that hyperpolarization participates in the regulation of resting vasodilator tone and vascular reactivity in healthy subjects. In addition, an enhanced endothelium-derived hyperpolarization contributes to both resting and agonist-stimulated vasodilation in a variety of cardiovascular risk conditions and disease. Thus, hyperpolarization mediated by epoxyeicosatrienoic acids (EETs) and H2 O2 has been observed in coronary arterioles of patients with coronary artery disease. Similarly, ouabain-sensitive and EETs-mediated hyperpolarization has been observed to compensate for NO deficiency in patients with essential hypertension. Moreover, in non-hypertensive patients with multiple cardiovascular risk factors and in hypercholesterolaemia, KCa channel-mediated vasodilation appears to be activated. A novel paradigm establishes that perivascular adipose tissue (PVAT) is an additional regulator of vascular tone/function and endothelium is not the only agent in vascular hyperpolarization. Indeed, some PVAT-derived relaxing substances, such as adiponectin and angiotensin 1-7, may exert anticontractile and vasodilator actions by the opening of KCa channels in smooth muscle cells. Conversely, PVAT-derived factors impair coronary vasodilation via differential inhibition of some K(+) channels. In view of adipose tissue abnormalities occurring in human obesity, changes in PVAT-dependent hyperpolarization may be relevant for vascular dysfunction also in this condition
Endothelial and perivascular adipose tissue abnormalities in obesity-related vascular dysfunction: novel targets for treatment
No full textABSTRACT: The heavy impact of obesity on the development and progression of cardiovascular disease has sparked sustained efforts to uncover the mechanisms linking excess adiposity to vascular dysfunction. In addition to its well-established role in maintaining vascular homeostasis, the endothelium has been increasingly recognized as a key player in modulating healthy adipose tissue expansion in response to excess calories by providing adipocyte precursors and driving angiogenesis. When this increased storage need is unmet, excessive deposition of fat occurs at ectopic locations, including perivascular adipose tissue (PVAT). PVAT is in intimate contact with the vessel wall, hence affecting vascular function and structure. In lean individuals, PVAT exerts anti-contractile and anti-inflammatory activities to protect the vasculature. In obesity, instead, these beneficial properties are lost and PVAT releases inflammatory mediators, promotes oxidative stress and contributes to vascular dysfunction. The underlying mechanisms elicited by these outside-in signals include resistance to the vasodilator actions of insulin and activation of endothelin ET-1-mediated vasoconstriction. A number of adipokines and gut hormones, which are important modulators of food intake, energy balance, glucose and lipid metabolism, insulin sensitivity and inflammation, have also positive vascular actions. This feature makes them promising tools for targeting both the metabolic and cardiovascular complications of obesity, a view supported by recent large-scale clinical trials indicating that novel drugs for type 2 diabetes with cardiovascular potential may translate into clinically significant benefits. There is, therefore, real hope that unleashing the power of fat- and gut-derived substances might provide effective dual-action therapies for obesity and its complications
Erratum to: Effect of moderate red wine intake on cardiac prognosis after recent acute myocardial infarction of subjects with Type 2 diabetes mellitus (Diabetic Medicine, (2006), 23, 9, (974-981), 10.1111/j.1464-5491.2006.01886.x)
No full textIn an article by Marfella et al, the author name C. Saron is incorrect and should be listed as C. Sardu. Therefore the correct author list is: R. Marfella, F. Cacciapuoti, M. Siniscalchi, F. C. Sasso, F. Marchese, F. Cinone, E. Musacchio, M. A. Marfella, L. Ruggiero, G. Chiorazzo, D. Liberti, G. Chiorazzo, G. F. Nicoletti, C. Sardu, F. D'Andrea, C. Ammendola, M. Verza and L. Coppola.In an article by Marfella et al, the author name C. Saron is incorrect and should be listed as C. Sardu. Therefore the correct author list is: R. Marfella, F. Cacciapuoti, M. Siniscalchi, F. C. Sasso, F. Marchese, F. Cinone, E. Musacchio, M. A. Marfella, L. Ruggiero, G. Chiorazzo, D. Liberti, G. Chiorazzo, G. F. Nicoletti, C. Sardu, F. D'Andrea, C. Ammendola, M. Verza and L. Coppola
Cardiovascular and metabolic effects of ghrelin
No full textGhrelin is an orexigenic peptide hormone secreted into the systemic circulation predominantly by the X/A-like cells in the mucosa of the stomach. In addiction to central effects on food intake and growth hormone release, ghrelin has also important vascular and metabolic actions. Our laboratory has shown that administration of exogenous ghrelin acutely improves endothelial function by increasing nitric oxide bioavailability and normalizing the alterate balance between endothelin 1/nitric oxide (ET-1/NO) within the vasculature of individuals with metabolic syndrome. Additionally, in endothelial cell cultures, it has been shown that ghrelin directly stimulates NO production using a signaling pathway that involves GHSR-1a, PI 3-kinase, Akt, and eNOS. Other cardiovascular effects of ghrelin include lowering of peripheral resistance, improvement of contractility and cardiac output. In addition ghrelin plays a significant role in the regulation of glucose homeostasis, lipid profiles and body composition. Importantly, ghrelin has antinflammatory and antiapoptotic effects both in vivo and in vitro. This review focuses on the physiological roles of ghrelin in regulating metabolic and endothelial function and on the potential of ghrelin as the therapeutic target to treat metabolic and cardiovascular disorders
Vascular effects of insulin and their relation to endothelial dysfunction, insulin resistance and hypertension
No full textIncreased fractalkine and vascular dysfunction in obesity and in type 2 diabetes. Effects of oral antidiabetic treatment
No full textActivation of fractalkine and other chemokines plays an important role in atherogenesis and, in conjunction with endothelial dysfunction, promotes premature vascular damage in obesity and diabetes. We hypothesized that increased circulating fractalkine coexists with impaired vasomotor function in metabolically healthy or unhealthy obesity, and that treatment with antidiabetic drugs may impact these abnormalities in type 2 diabetes. Compared to lean subjects, in both obese groups the vasodilator responses to acetylcholine and sodium nitroprusside were impaired (both P < .001); ETA-receptor blockade resulted in greater vasodilation (both P < .001); and plasma levels of fractalkine, E-selectin and monocyte chemoattractant protein (MCP)-1 were increased (all P < .05). In diabetic patients, oral antidiabetic drugs (glyburide, metformin or pioglitazone) reduced circulating levels fractalkine and E-selectin (both P < .05), without affecting vascular responses (all P > .05). Our findings indicate that insulin resistant states are associated with elevated atherogenic chemokines and impaired vascular reactivity. Antidiabetic treatment results in lower circulating fractalkine, which may provide cardiovascular benefits
SPATIAL NONSTATIONARITY IN THE STOCHASTIC FRONTIER MODEL: AN APPLICATION TO THE ITALIAN WINE INDUSTRY
No full textDiagnostic Performance of F-18-Fluorodeoxyglucose in 162 Small Pulmonary Nodules Incidentally Detected in Subjects Without a History of Malignancy
No full textBackground. Solitary pulmonary nodule (SPN) still represents a diagnostic challenge. The aim of our study was to evaluate the diagnostic performance of F-18-fluorodeoxyglucose positron emission tomography-computed tomography in one of the largest samples of small SPNs, incidentally detected in subjects without a history of malignancy (nonscreening population) and undetermined at computed tomography. Methods. One-hundred and sixty-two small (>0.8 to 1.5 cm) and, for comparison, 206 large nodules (>1.5 to 3 cm) were retrospectively evaluated. Diagnostic performance of F-18-fluorodeoxyglucose visual analysis, receiver operating characteristic (ROC) analysis for maximum standardized uptake value (SUVmax), and Bayesian analysis were assessed using histology or radiological follow-up as a golden standard. Results. In 162 small nodules, F-18-fluorodeoxyglucose visual and ROC analyses (SUVmax = 1.3) provided 72.6% and 77.4% sensitivity and 88.0% and 82.0% specificity, respectively. The prevalence of malignancy was 38%; Bayesian analysis provided 78.8% positive and 16.0% negative posttest probabilities of malignancy. In 206 large nodules F-18-fluorodeoxyglucose visual and ROC analyses (SUVmax = 1.9) provided 89.5% and 85.1% sensitivity and 70.8% and 79.2% specificity, respectively. The prevalence of malignancy was 65%; Bayesian analysis provided 85.0% positive and 21.6% negative posttest probabilities of malignancy. In both groups, malignant nodules had a significant higher SUVmax (p < 0.0001) than benign nodules. Only in the small group, malignant nodules were significantly larger (p = 0.0054) than benign ones. Conclusions. F-18-fluorodeoxyglucose can be clinically relevant to rule in and rule out malignancy in undetermined small SPNs, incidentally detected in nonscreening population with intermediate pretest probability of malignancy, as well as in larger ones. Visual analysis can be considered an optimal diagnostic criterion, adequately detecting a wide range of malignant nodules with different metabolic activity. (C) 2016 by The Society of Thoracic Surgeon
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