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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The adipocyte-derived hormone adiponectin has been shown to play important roles in the regulation of energy homeostasis and insulin sensitivity. In this study, we analyzed globular domain adiponectin (gAd) transgenic (Tg) mice crossed with leptin-deficient ob/ob or apoE-deficient mice. Interestingly, despite an unexpected similar body weight, gAd Tg ob/ob mice showed amelioration of insulin resistance and beta-cell degranulation as well as diabetes, indicating that globular adiponectin and leptin appeared to have both distinct and overlapping functions. Amelioration of diabetes and insulin resistance was associated with increased expression of molecules involved in fatty acid oxidation such as acyl-CoA oxidase, and molecules involved in energy dissipation such as uncoupling proteins 2 and 3 and increased fatty acid oxidation in skeletal muscle of gAd Tg ob/ob mice. Moreover, despite similar plasma glucose and lipid levels on an apoE-deficient background, gAd Tg apoE-deficient mice showed amelioration of atherosclerosis, which was associated with decreased expression of class A scavenger receptor and tumor necrosis factor alpha. This is the first demonstration that globular adiponectin can protect against atherosclerosis in vivo. In conclusion, replenishment of globular adiponectin may provide a novel treatment modality for both type 2 diabetes and atherosclerosis.
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PMID:Globular adiponectin protected ob/ob mice from diabetes and ApoE-deficient mice from atherosclerosis. 1243 86

The aging process is characterized by a number of gradual changes in circulating hormone concentrations as well as a gradual increase in the degree of atherosclerosis. The authors studied whether serum hormone levels are related to atherosclerosis of the carotid artery in independently living, elderly men. In 1996, 403 men (aged 73-94 years) were randomly selected from the general population of Zoetermeer, the Netherlands. Carotid artery intima-media thickness was determined. Serum concentrations of testosterone; estrone; estradiol; dehydroepiandrosterone and dehydroepiandrosterone sulfate; insulin-like growth factor I (IGF-I) (total and free) and its binding proteins IGFBP-1, IGFBP-2, and IGFBP-3; and leptin were measured. After the authors adjusted for age, serum testosterone, estrone, and free IGF-I were inversely related to intima-media thickness. The strength of these relations was as powerful in subjects with as in those without prevalent cardiovascular disease. Serum estradiol; dehydroepiandrosterone sulfate; total IGF-I, IGFBP-1, IGFBP-2, and IGFBP-3; and leptin showed no association. These findings suggest that endogenous testosterone, estrone, and free IGF-I levels may play a protective role in the development of atherosclerosis in aging men.
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PMID:Endogenous hormones and carotid atherosclerosis in elderly men. 1250 87

Many studies have shown that fat distribution influences metabolism independently of the effects of total body fat stores. The accumulation of fat in the abdominal area, particularly in the visceral fat compartment, seems to be associated with an increased risk to display complications such as insulin resistance, diabetes, dyslipidemias and atherosclerosis. As reviewed in this paper, the mechanisms explaining this impact of fat distribution is not clearly established, although evidence suggests that free-fatty acids, leptin, TNF-alpha, PPAR-gamma, and F are directly or indirectly involved in this process. Despite a lot of research has yet to be performed to mechanistically characterize the impact of visceral fat on the metabolic profile, there is enough consensus in the literature about its effect to justify its consideration in a clinical setting. In this regard, the use of waist circumference as a clinical marker of variations in visceral fat is highly relevant and should be encouraged. This review also presents an evolutionary perspective according to which body fat gain would have been and may still remain an adaptation that helps to deal with stress and inflammation.
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PMID:Metabolic impact of body fat distribution. 1250 50

Obesity induced by long-term consumption of a fat-rich diet causes marked endothelial dysfunction. In this study we aimed to determine whether endothelial impairment is due to obesity or the diet per se. Wistar rats were fed either standard laboratory chow throughout (controls), or given a highly palatable diet (diet-fed) for 3 days, or fed the diet for 3 days and then returned to chow for 3 further days before sacrifice (diet-to-chow). Body weight, fat and gastrocnemius muscle mass, and plasma levels of glucose, insulin and leptin were all comparable between the three groups. Diet-fed rats had significantly raised plasma non-esterified fatty acids (NEFA; P=0.0005) and triglyceride levels (P=0.00001). The diet-to-chow group had intermediate plasma NEFA and triglyceride levels (significantly higher than in controls, P=0.019 and P=0.0035 for NEFA and triglycerides, respectively). There were no changes in noradrenaline and KCl responses in mesenteric arteries, whereas vasorelaxation to both carbamylcholine and sodium nitroprusside were significantly attenuated in the diet-fed group (by up to 18%; P=0.00001). Both these responses remained largely impaired in the diet-to-chow group. By contrast, histamine-induced vasorelaxation was comparable between all three groups. Thus, short-term feeding with a palatable diet induces marked endothelium-dependent and -independent arterial dysfunction. These effects occurred in the absence of obesity and largely persisted after removal of the palatable diet. Diet per se can have important detrimental effects on arterial function, which may be mediated by raised NEFA and/or triglyceride levels.
Atherosclerosis 2003 Feb
PMID:Prolonged endothelial-dependent and -independent arterial dysfunction induced in the rat by short-term feeding with a high-fat, high-sucrose diet. 1253 37

Insulin resistance is involved in the pathogenesis of type 2 diabetes, hypertension, and atherosclerosis. Angiotensin (Ang) converting enzyme inhibitors and Ang II type 1 receptor antagonists improve insulin resistance in patients with essential hypertension, which suggest that tissue Ang II is involved in insulin resistance in patients with hypertension. To investigate the participation of tissue Ang II in insulin resistance associated with hypertension, we evaluated the Ang II-generating system in leukocytes and its relation to insulin resistance in patients with essential hypertension. Eighteen patients with essential hypertension participated in this study. Ang II was separated from leukocytes by reversed-phase high-performance liquid chromatography and measured by radioimmunoassay. Insulin resistance was evaluated by determining the steady-state of plasma glucose (SSPG) concentration. The Ang I- and Ang II-generating activities were evaluated in human leukocytes. Human leukocytes have Ang I- and Ang II-generating activities. The Ang II-generating activity was significantly inhibited by pepstatin A. Leukocyte Ang II level does not correlate with BP or plasma Ang II level in patients with essential hypertension. Leukocyte Ang II level strongly correlates with SSPG concentration, and significantly correlates with body mass index and plasma insulin, and with leptin levels in patients with essential hypertension. Leukocyte Ang II may be directly associated with insulin resistance.
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PMID:Leukocyte angiotensin II levels inpatients with essential hypertension:relation to insulin resistance. 1255 79

The prevalence of obesity is rising at an alarming rate worldwide, with consequent increases in type 2 diabetes, hypertension and cardiovascular morbidity and mortality. Central neural mechanisms, via the activation of the sympathetic nervous system may contribute to obesity-related cardiovascular diseases through the promotion of hypertension, dysrhythmia and atherosclerosis. However, the mechanisms responsible for this sympatho activation have not been identified. Leptin is an adipocyte-derived hormone that promotes weight loss by reducing appetite and by increasing energy expenditure through sympathetic stimulation to thermogenic tissue. Leptin also produces sympathoactivation to kidneys, hindlimb and adrenal glands, suggesting that the obesity-associated increase in sympathetic nerve activity could be due in part to these sympathetic effects of leptin. However, most human obesity appears to be associated with leptin resistance. Recent studies indicate that leptin resistance may be selective, with preservation of adverse sympathetic effects despite the loss of the metabolic actions of leptin. The leptin receptor is expressed in several hypothalamic nuclei including the arcuate nucleus. The melanocortin system, neuropeptide Y and corticotrophin-releasing factor have emerged as principal neuropeptide mediators of leptin action in the arcuate nucleus. These neuropeptides exert varying effects by different pathways. Several other candidate hypothalamic pathways that can mediate the effects of leptin have been identified. The understanding of neuronal signaling pathways involved in leptin signaling and energy balance has opened new research possibilities for the treatment of obesity.
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PMID:Leptin and the central neural mechanisms of obesity hypertension. 1258 70

Adipose tissue is a necessary survival characteristic of species that do not have constant access to food. TNF-alpha is a very fundamental "internal regulator" (intra-system) of adipose tissue metabolism, and IL-6 and IL-1 beta are relevant control factors, as well. Leptin and IL-6, but not TNF-alpha, appear to be the major signals linking adipose tissue to the systemic immunologic response. In ESRD, it has been coherently observed that acute-phase reactants like CRP and serum amyloid A are independently associated to atherosclerosis, death, and cardiovascular complications. Leptin is inversely related with plasma creatinine, suggesting that reduced renal clearance is a primary factor responsible for hyperleptinemia in ESRD. On the other hand, this adipose tissue hormone behaves as an inverse acute-phase reactant (i.e., it decreases during spontaneous episodes of the acute-phase response). Dialysis patients with hyperleptinemia have more severe degrees of insulin resistance but further studies are required to see whether leptin plays a role in insulin resistance in these patients. The most abundant protein synthesized in the adipose tissue, adiponectin, is inversely related to metabolic risk factors like glucose, triglycerides, insulin, and HDL cholesterol in uremic patients, suggesting that this cytokine is a protective factor for the cardiovascular system. Accordingly, plasma adiponectin is an independent, inverse predictor of incident cardiovascular events in dialysis patients.
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PMID:Adipose tissue as a source of inflammatory cytokines in health and disease: focus on end-stage renal disease. 1269 12

A significant and independent association between endogenous testosterone (T) levels and coronary events in men and women has not been confirmed in large prospective studies, although cross-sectional data have suggested coronary heart disease can be associated with low T in men. Hypoandrogenemia in men and hyperandrogenemia in women are associated with visceral obesity; insulin resistance; low high-density lipoprotein (HDL) cholesterol (HDL-C); and elevated triglycerides, low-density lipoprotein cholesterol, and plasminogen activator type 1. These gender differences and confounders render the precise role of endogenous T in atherosclerosis unclear. Observational studies do not support the hypothesis that dehydroepiandrosterone sulfate deficiency is a risk factor for coronary artery disease. The effects of exogenous T on cardiovascular mortality or morbidity have not been extensively investigated in prospective controlled studies; preliminary data suggest there may be short-term improvements in electrocardiographic changes in men with coronary artery disease. In the majority of animal experiments, exogenous T exerts either neutral or beneficial effects on the development of atherosclerosis. Exogenous androgens induce both apparently beneficial and deleterious effects on cardiovascular risk factors by decreasing serum levels of HDL-C, plasminogen activator type 1 (apparently deleterious), lipoprotein (a), fibrinogen, insulin, leptin, and visceral fat mass (apparently beneficial) in men as well as women. However, androgen-induced declines in circulating HDL-C should not automatically be assumed to be proatherogenic, because these declines may instead reflect accelerated reverse cholesterol transport. Supraphysiological concentrations of T stimulate vasorelaxation; but at physiological concentrations, beneficial, neutral, and detrimental effects on vascular reactivity have been observed. T exerts proatherogenic effects on macrophage function by facilitating the uptake of modified lipoproteins and an antiatherogenic effect by stimulating efflux of cellular cholesterol to HDL. In conclusion, the inconsistent data, which can only be partly explained by differences in dose and source of androgens, militate against a meaningful assessment of the net effect of T on atherosclerosis. Based on current evidence, the therapeutic use of T in men need not be restricted by concerns regarding cardiovascular side effects. Available data also do not justify the uncontrolled use of T or dehydroepiandrosterone for the prevention or treatment of coronary heart disease.
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PMID:Androgens and coronary artery disease. 1270 Jan 79

Advanced glycation end products (AGEs) and other carbonyl and oxidative stress compounds are supposed to play a critical role in the pathogenesis of several diseases and their complications, i.e., diabetes mellitus, diabetic retinopathy, atherosclerosis, and chronic renal failure. In the present investigation, we were interested in the relationship of AGEs in plasma to other prominent factors in the patients on chronic hemodialysis treatment-27 patients with diabetes mellitus, 35 patients without diabetes mellitus. AGE-group reactivity was estimated using a spectrofluorometric method (excitation 350 nm, emission 430 nm) and is expressed in arbitrary units (AU). We found significantly higher AGEs levels in diabetics than in non-diabetics on regular hemodialysis treatment both before (2.7 +/- 0.7 x 10(4) AU vs. 2.2 +/- 0.6 x 10(4) AU, p < 0.001) and after the dialysis session (2.3 +/- 0.5 x 10(4) AU vs. 1.8 +/- 0.7 x 10(4) AU, p < 0.005). AGEs were significantly reduced during hemodialysis in both groups of patients--by 15.4% in the diabetic go (p < 0.001) and by 17.3% in non-diabetics (p < 0.005). In the patients with diabetes mellitus, AGEs did not correlate with parameters of the glucose metabolism correction (blood glucose, HbA1c). We observed a significant correlation between AGEs and leptin (r = 0.48, p < 0.05) as well as the leptin/body fat ratio (r = 0.56, p < 0.05) only in hemodialyzed patients with diabetes mellitus. These findings suggest more detailed studies to identify the molecular links between carbonyl stress, i.e., advanced glycation end products, and leptin metabolism, sign of microinflammation and hypertension.
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PMID:Advanced glycation end products in hemodialyzed patients with diabetes mellitus correlate with leptin and leptin/body fat ratio. 1273 34

Conjugated linoleic acid (CLA) is a mixture of positional and geometric isomers of linoleic acid found in beef, lamb, and dairy products. CLA has attracted considerable attention over the past several decades because of its potentially beneficial biological effects, including protective effects against several cancers, atherosclerosis, and obesity. Here we provide the first evidence that the 10trans,12cis-CLA isomer is able to suppress increases in blood pressure during the onset of obesity in OLETF rats. After 3 weeks of feeding with 10t,12c-CLA, systolic blood pressure was significantly lowered compared with rats fed linoleic acid or 9c,11t-CLA. Abdominal adipose tissue weight was also significantly lowered in rats fed 10t,12c-CLA, but not in those which were fed 9c,11t-CLA. In addition, we found that the relative mRNA expressions of angiotensinogen and leptin were suppressed by 10t,12c-CLA in adipose tissue. We speculate that the antihypertensive effect of 10t,12c-CLA can be attributed to the lowered secretion of hypertensive adipocytokines from abdominal adipose tissues.
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PMID:The 10trans,12cis isomer of conjugated linoleic acid suppresses the development of hypertension in Otsuka Long-Evans Tokushima fatty rats. 1278 78


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