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

The pathophysiology of insulin resistance and atherosclerosis may share a common inflammatory basis, maintaining endothelial dysfunction, suggesting why patients with T2DM (Type II diabetes mellitus) have an impaired prognosis after an MI (myocardial infarction), but it remains unclear how these parameters are inter-related. Forty patients with an MI (20 patients with and 20 patients without T2DM) took part in this cross-sectional study. Endothelium-dependent [FMD (flow-mediated dilation)] and -independent [NTG (nitroglycerine)] vasodilatation (determined by ultrasound), S(I) (insulin sensitivity index; determined by isoglycaemic-hyperinsulinaemic clamp) and serum levels of CRP (C-reactive protein), TNF-alpha (tumour necrosis factor-alpha), IL-6 (interleukin 6), resistin and adiponectin (determined by ELISA) were measured. Associations between FMD/NTG and S(I), and CRP, TNF-alpha, IL-6, adiponectin, resistin, lipids, blood pressure, BMI (body mass index) and brachial artery diameter were then assessed. FMD (2.1 compared with 4.7%; P<0.05), NTG (14.9 compared with 21.2%; P<0.05) and S(I) [4.3 compared with 6.6 10(-4) dl.kg(-1) of body weight.min(-1).(mu-units/ml)(-1); P<0.05], and adiponectin levels (3.1 compared with 6.4 microg/ml; P<0.01) were all lower in patients with T2DM. TNF-alpha (6.9 compared with 1.8 pg/ml; P<0.01) and IL-6 (2.3 compared with 1.2 pg/ml; P<0.01) levels were higher in patients with T2DM, whereas differences in CRP and resistin levels did not attain statistical significance between the two groups. TNF-alpha concentrations and brachial artery diameter were negatively, whereas S(I) was positively, correlated with FMD. Adjustment for age weakened the association for S(I), whereas TNF-alpha and brachial artery diameter remained significantly associated with FMD after adjustment for group, age and BMI. Endothelial dysfunction and low-grade inflammation co-exist in T2DM after MI. These results suggest that the endothelium is negatively impacted in multiple ways by the diabetic state after an MI.
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PMID:Increased levels of tumour necrosis factor-alpha (TNF-alpha) in patients with Type II diabetes mellitus after myocardial infarction are related to endothelial dysfunction. 1646 46

Visceral obesity is among the known risk factors of atherosclerotic cardiovascular diseases. As long as adipose tissue was considered only an inert store of excess energy, accumulated in triglycerides, explanation of the mechanisms causing increased cardiovascular risk in obesity was difficult. Finding that the adipose tissue is an active endocrine organ and that the adipokines secreted in it influence several metabolic processes, allowed better understanding of this correlation. Several disturbances in secretion, function and balance of adipokines occur in the course of obesity. Changes of adiponectin, leptin and resistin concentrations are among the reasons of accelerated atherosclerosis occurring in the visceral adiposity. Adiponectin concentrations are decreased in visceral adiposity. Adiponectin is adipokine possessing antiatherogenic properties. It's effects exerted though the specific receptors in skeletal muscles and liver include decreased insulin resistance and improved plasma lipid profile. Acting directly in the vessel wall adiponectin prevents development of atheromatic lesions by inhibiting production of adhesive molecules and formation of foam cells. It has been found that decreased adiponectin concentrations are connected not only with increased coronary risk but also with progression of atherosclerosis in coronary vessels. Moreover it was found that adiponectin plasma concentration is significantly decreased in acute coronary incidences. Leptin regulates energy metabolism and balance. The concentrations of this adipokine are increased in obesity and correlate with insulin resistance. Hiperleptinemia has been also recognized as cardiovascular diseases risk factor. Resistin is considered to be a substance increasing insulin resistance, however the exact mechanisms are not known. Resistin plasma concentrations are increased in obese subjects and correlate with the inflammatory state that underlies the initiation and progression of atherosclerotic lesions. Correlation between resistin concentration and the extent of atherosclerotic plaques in the coronary vessels has also been found. The disturbances in secretion, function and balance of adiponectin, leptin and resistin are to be considered not only a link between visceral adiposity and cardiovascular risk but also independent risk factor of coronary heart disease.
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PMID:[Adipokines: adiponectin, leptin, resistin and coronary heart disease risk]. 1652 24

Resistin is a newly identified adipocyte secreted hormone belonging to a cysteine-rich protein family. It is expressed in white adipose tissues in rodents and has also been found in several other tissues in human. Insulin, glucose, many cytokines and anti-diabetic thiazolidinediones are regulators of resistin gene expression. Resistin was firstly proposed to be involved in insulin resistance and type 2 diabetes. Recently, it was found to be relevant to inflammation and inflammation-related diseases like atherosclerosis and arthritis.
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PMID:Role of resistin in inflammation and inflammation-related diseases. 1654 46

Adipose tissue secretes bioactive peptides, termed 'adipokines', which act locally and distally through autocrine, paracrine and endocrine effects. In obesity, increased production of most adipokines impacts on multiple functions such as appetite and energy balance, immunity, insulin sensitivity, angiogenesis, blood pressure, lipid metabolism and haemostasis, all of which are linked with cardiovascular disease. Enhanced activity of the tumour necrosis factor and interleukin 6 are involved in the development of obesity-related insulin resistance. Angiotensinogen has been implicated in hypertension and plasminogen activating inhibitor-1 (PAI-1) in impaired fibrinolysis. Other adipokines like adiponectin and leptin, at least in physiological concentrations, are insulin sparing as they stimulate beta oxidation of fatty acids in skeletal muscle. The role of resistin is less understood. It is implicated in insulin resistance in rats, but probably not in humans. Reducing adipose tissue mass, through weight loss in association with exercise, can lower TNF-alpha and IL-6 levels and increase adiponectin concentrations, whereas drugs such as thiazolinediones increase endogenous adiponectin production. In-depth understanding of the pathophysiology and molecular actions of adipokines may, in the coming years, lead to effective therapeutic strategies designed to protect against atherosclerosis in obese patients.
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PMID:The endocrine function of adipose tissue: an update. 1658 5

Normal metabolic balance is maintained by a complex homeostatic system involving multiple tissues and organs. Acquired or inherited defects associated to environmental factors in any part of this system can lead to metabolic disorders such as the syndrome X which is presently a frequent syndrome in industrialized countries. It is characterized by a cluster of risk factors of atherosclerosis including insulin resistance, hyperinsulinemia, impaired glucose tolerance or type 2 diabetes, hypertension, dyslipidemia, and coagulation abnormalities. Its pathophysiology is likely to involve insulin resistance at the level of both skeletal muscle and visceral adipose tissue and altered fluxes of metabolic substrates between these tissues that in turn impair liver metabolism. Therapeutic intervention favours at present diet and exercise prescriptions. In addition, if necessary, specific treatment of the metabolic disorders is required. In the treatment of insulin resistance, new promising drugs are likely to be used in the next future. In this regard, adipose tissue, once thought to function primarily as a passive depot for the storage of excess lipid, is now understood to play a much more active role in metabolic regulation, secreting a variety of metabolic hormones and actively functioning to prevent deleterious lipid accumulation in other tissues and to modulate the insulin resistance. Here, we review new advances in our understanding of mechanisms leading to insulin resistance and type 2 diabetes from the perspective of the role and interactions of recently identified adipocyte-specific chemical messengers, the adipocytokines, such as adiponectin, tumor necrosis factor-alpha, interleukin 6, and resistin.
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PMID:[Adipocytokins, obesity and development of type 2 diabetes]. 1659 99

Resistin is a 12.5-kDa polypeptide hormone produced by adipocytes and immunocompetent cells. It was originally proposed as a link between obesity and insulin resistance/diabetes. Later, studies revealed that substantial inter-species differences exist between the major sites of resistin production in rodents (adipocytes) and humans (immunocompetent cells). While in rodents resistin appears to have an important role in the development of liver insulin resistance, its role in humans is less clear, and it is probably involved in the regulation of inflammatory processes rather than in insulin sensitivity. Current experimental and clinical data concerning resistin physiology and pathophysiology, and its possible role in the development of insulin resistance and atherosclerosis are detailed in this review.
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PMID:The role of resistin in obesity-induced insulin resistance. 1662 16

Endothelial dysfunction is associated with several vascular conditions as atherosclerosis, hypertension, hyperlipidemia and diabetes mellitus. In all these conditions insulin resistance (IR) is present. Cytokines are low molecular weight proteins with several endocrine and metabolic functions that participate of inflammation and immune response. Several of these cytokines are independent risk factors for cerebrovascular and coronary artery disease. The major sources of cytokines (adipokines) are the visceral and subcutaneous adipose tissues. Thus, increased adipose tissue mass is associated with alteration in adipokine production as over expression of tumor necrosis factor alpha, interleukin 6, plasminogen activator inhibitor 1, and under expression of adiponectin in adipocite tissue. The pro-inflammatory status associated with these changes provides a potential link between IR and endothelial dysfunction, the early stage in the atherosclerotic process, in obese individuals, and type 2 diabetic patients. Reduction of adipose tissue mass through weight reduction in association with exercise reduces TNF-alpha, IL-6, and PAI-1, increases adiponectin, and is associated with improved insulin sensitivity and endothelial function. This review will focus on the evidence for regulation of endothelial function by insulin and the adypokines such as adyponectin, leptin, resistin, IL-6 and TNF-alpha. Interaction between insulin signaling and adypokines will be discussed, as well as the concept that aberrant adypokine secretion in IR and/or obesity impairs endothelial function and contributes further to reduce insulin sensitivity.
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PMID:[Cytokines, endothelial dysfunction, and insulin resistance]. 1676 96

Adipokines may serve as an important etiologic link between atherosclerosis and obesity. Because adipose tissue is one site of action of the lipid-lowering drug niacin, we investigated whether niacin treatment would affect not only lipids but also adipokines. Twenty-four patients were treated with extended-release niacin. During the first 4 weeks the daily dose was increased at weekly intervals from 375 to 1000 mg, which was maintained for 4 weeks. Thereafter, the dose was 1500 mg for another 6 weeks. Adiponectin increased by 54% and 94%, respectively, resistin was lowered only moderately, and leptin not at all. Because adiponectin has repeatedly been shown to be negatively associated with atherosclerotic risk, its pronounced increase may bring about additional atheroprotection by niacin beyond its improvement in lipids.
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PMID:Adipokines and treatment with niacin. 1697 96

Excessive lipid accumulation in macrophages plays an important role in the development of atherosclerosis. Recently, several studies have implied that resistin, an adipocytokine which is mainly expressed in human peripheral blood monocytes, may take part in the pathogenesis of atherosclerosis. In this study, we investigated the effects of resistin on lipid accumulation as well as oxLDL on resistin expression in human macrophages. Treatment of macrophages with oxLDL significantly increased resistin mRNA expression, whereas native LDL had no such effect. Resistin pre-treated macrophages contained more and larger lipid droplets stained by Nile red. Resistin increased the expression of CD36 at both mRNA and protein levels, without affecting those of class A macrophage scavenger receptor (SR-A). These results suggest that resistin promotes lipid accumulation in human macrophages through its upregulating CD36 cell surface expression. Also, it is suggested that resistin may act as a modulator for macrophage-to-foam cell transformation.
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PMID:Resistin increases lipid accumulation and CD36 expression in human macrophages. 1706 53

Population-based studies have shown strong relationship between inflammatory markers and metabolic disturbances, obesity, and atherosclerosis, whereas inflammation has been considered as a "common soil" between these clinical entities and type 2 diabetes (T2D). The accumulation of macrophages in adipose tissue (AT), the common origin of macrophages and adipocytes, the prevalent presence of peripheral mononuclear cells, and apoptotic beta cells by themselves seem to be the sources of inflammation present in T2D, since they generate the mediators of the inflammatory processes, namely cytokines. The main cytokines involved in the pathogenesis of T2D are interleukin-1beta (IL-1beta), with an action similar to the one present in type 1 diabetes, tumor necrosis factor-alpha (TNF-alpha), and IL-6, considered as the main regulators of inflammation, leptin, more recently introduced, and several others, such as monocyte chemoattractant protein-1, resistin, adiponectin, with either deleterious or beneficial effects in diabetic pathogenesis. The characterization of these molecules targeted diabetes treatment beyond the classical interventions with lifestyle changes and pharmaceutical agents, and toward the determination of specific molecular pathways that lead to low grade chronic inflammatory state mainly due to an immune system's unbalance.
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PMID:Inflammatory process in type 2 diabetes: The role of cytokines. 1715 Dec 95


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