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

The childhood obesity epidemic has begun to compromise the health of the pediatric population by promoting premature development of atherosclerosis and the metabolic syndrome (MS), both of which significantly increase the risk of cardiovascular disease (CVD) early in life. As a result, recently, there has been increased recognition of the need to assess and closely monitor children and adolescents for risk factors of CVD and components of the MS. Serum/Plasma biomarkers including total cholesterol, triglycerides, HDL-C, LDL-C, insulin and C-peptide have been used for this purpose for many years. Recently, emerging biomarkers such as apolipoprotein AI, apolipoprotein B, leptin, adiponectin, free fatty acids, and ghrelin have been proposed as tools that provide valuable complementary information to that obtained from traditional biomarkers, if not more powerful predictions of risk. In order for biomarkers to be clinically useful in accurately diagnosing and treating disorders, age-specific reference intervals that account for differences in gender, pubertal stage, and ethnic origin are a necessity. Unfortunately, to date, many critical gaps exist in the reference interval database of most of the biomarkers that have been identified. This review contains a comprehensive gap analysis of the reference intervals for emerging and traditional risk biomarkers of CVD and the MS and discusses the clinical significance and analytical considerations of each biomarker.
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PMID:Gap analysis of pediatric reference intervals for risk biomarkers of cardiovascular disease and the metabolic syndrome. 1662 72

Epidemiological data suggest a link between chronic inflammation condition and atherosclerosis. Infection and inflammation can also impair lipoprotein metabolism and produce a wide variety of changes in plasma concentrations of lipids and lipoproteins. Twenty-one patients with inflammatory bowel diseases (IBDs) and 28 healthy subjects were recruited. Serum concentrations of lipids, lipoproteins, apolipoproteins, leptin, ghrelin, and inflammation markers (C-reactive protein and serum amyloid A) were measured, and subjects' lipoproteins were characterized. The ability of patients with serum IBD to efflux free cell cholesterol was measured. Serum cholesterol, high-density lipoprotein cholesterol, apolipoprotein (apo) A-I, apoC-II, apoC-III bound to apoB, phospholipid, and phospholipids not bound to apoB levels were significantly lower, whereas serum triglyceride, serum amyloid A, and C-reactive protein levels were significantly higher in patients with active IBD. Apolipoprotein A-I immunoreactivity (pre-beta small particles and small alpha-high-density lipoprotein particles) is decreased in patients with IBD. In contrast, apoE immunoreactivity (slow/small apoE containing lipoprotein particles [LpE particle]) increased in these patients. The efflux capacity of serum from patients with IBD using [(3)H]-cholesterol-labeled Fu5AH cells was reduced (P < .005). Our results demonstrate that, in subjects with active IBD, inflammation leads to alterations in lipid, apolipoprotein, and lipoprotein profiles and reduced cholesterol efflux. These changes are similar to those proposed to promote atherogenesis and may contribute to the development of cardiovascular events.
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PMID:Altered lipid, apolipoprotein, and lipoprotein profiles in inflammatory bowel disease: consequences on the cholesterol efflux capacity of serum using Fu5AH cell system. 1678 73

Ghrelin, the endogenous ligand for the GH secretagogue receptor, is produced by the oxyntic cells of the stomach and is involved in the regulation of energy balance. However, an increasing number of direct ghrelin cardiovascular effects, and, among them, high ghrelin binding in atherosclerotic coronary arteries, are being reported. We investigated whether ghrelin affects migration of human aorta endothelial cells (HAEC). HAEC bound ghrelin in specific, saturable manner. Ghrelin, as such, did not affect HAEC migration, however it inhibited the angiotensin II-induced migration, and this effect was inhibited by the antagonist (D-Lys(3))-GHRP-6. In HAEC, ghrelin elicited increased intracellular concentration of cAMP that was involved in its effect on AngII-induced HAEC migration, as the AMP cyclase inhibitor SQ22.536 and PKA inhibitor KT5720, respectively, inhibited and blunted it. These findings suggest a role of ghrelin in the control of endothelial cell migration and its possible involvement in vascular changes present in disorders characterized by low plasma ghrelin.
Atherosclerosis 2007 Jun
PMID:Ghrelin inhibits angiotensin II-induced migration of human aortic endothelial cells. 1694 80

Macrophages play a central role in the pathogenesis of atherosclerosis by accumulating cholesterol through increased uptake of oxidized low-density lipoproteins by scavenger receptor CD36, leading to foam cell formation. Here we demonstrate the ability of hexarelin, a GH-releasing peptide, to enhance the expression of ATP-binding cassette A1 and G1 transporters and cholesterol efflux in macrophages. These effects were associated with a transcriptional activation of nuclear receptor peroxisome proliferator-activated receptor (PPAR)gamma in response to binding of hexarelin to CD36 and GH secretagogue-receptor 1a, the receptor for ghrelin. The hormone binding domain was not required to mediate PPARgamma activation by hexarelin, and phosphorylation of PPARgamma was increased in THP-1 macrophages treated with hexarelin, suggesting that the response to hexarelin may involve PPARgamma activation function-1 activity. However, the activation of PPARgamma by hexarelin did not lead to an increase in CD36 expression, as opposed to liver X receptor (LXR)alpha, suggesting a differential regulation of PPARgamma-targeted genes in response to hexarelin. Chromatin immunoprecipitation assays showed that, in contrast to a PPARgamma agonist, the occupancy of the CD36 promoter by PPARgamma was not increased in THP-1 macrophages treated with hexarelin, whereas the LXRalpha promoter was strongly occupied by PPARgamma in the same conditions. Treatment of apolipoprotein E-null mice maintained on a lipid-rich diet with hexarelin resulted in a significant reduction in atherosclerotic lesions, concomitant with an enhanced expression of PPARgamma and LXRalpha target genes in peritoneal macrophages. The response was strongly impaired in PPARgamma(+/-) macrophages, indicating that PPARgamma was required to mediate the effect of hexarelin. These findings provide a novel mechanism by which the beneficial regulation of PPARgamma and cholesterol metabolism in macrophages could be regulated by CD36 and ghrelin receptor downstream effects.
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PMID:A growth hormone-releasing peptide that binds scavenger receptor CD36 and ghrelin receptor up-regulates sterol transporters and cholesterol efflux in macrophages through a peroxisome proliferator-activated receptor gamma-dependent pathway. 1695 72

Ghrelin may play a role in the development of atherosclerosis. However, the effect of serum ghrelin on carotid intima-media thickness (cIMT) (well-established as a surrogate marker to atherosclerosis) in metabolic syndrome (MS), particularly among relatively older subjects, has still not been thoroughly investigated. A total of 101 subjects >60 years of age (mean age, 72.3 years) with MS were enrolled in the study to investigate the relationship between serum total ghrelin and B-mode ultrasonographic cIMT levels. There were significantly positive correlations between cIMT and both age and systolic BP, but cIMT was significantly inversely correlated to ghrelin levels. In the multiple regression analysis for cIMT adjusted by other measured parameters, ghrelin was a significant and independent factor along with age and systolic BP. These findings suggest that decreased ghrelin levels may be related to carotid atherosclerosis among older subjects with MS.
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PMID:Serum ghrelin and carotid atherosclerosis in older Japanese people with metabolic syndrome. 1697 Dec 34

Ghrelin is a 28-amino-acid peptide with several functions linked to energy metabolism. Low ghrelin plasma concentrations are associated with obesity, hypertension, and type 2 diabetes mellitus, whereas high concentrations reflect states of negative energy balance. Several studies addressing the hormonal and neural regulation of ghrelin gene expression have been carried out, but the role of genetic factors in the regulation of ghrelin plasma levels remains unclear. To elucidate the role of genetic factors in the regulation of ghrelin expression, we screened 1657 nucleotides of the ghrelin gene 5' flanking region (promoter and possible regulatory sites) for new sequential variations from patient samples with low (n = 50) and high (n = 50) fasting plasma total ghrelin concentrations (low- and high-ghrelin groups). Eleven single nucleotide polymorphisms (SNPs), 3 of which were rare variants (allelic frequency less than 1%) were found in our population. The genotype distribution patterns of the SNPs did not differ between the study groups, except for SNP-501A>C (P = .039). In addition, the SNP-01A>C was associated with body mass index (BMI) (P = .018). This variant was studied further in our large and well-defined Oulu Project Elucidating Risk for Atherosclerosis (OPERA) cohort (n = 1045) by the restriction fragment length polymorphism (RFLP) technique. No significant association of SNP-501A>C genotypes with fasting ghrelin plasma concentrations was found in the whole OPERA population. However, the association of this SNP with BMI and with waist circumference reached statistical significance in OPERA (P = .047 and .049, respectively), remaining of borderline significance for BMI after adjustments (P = .055). The results indicate that factors other than the 11 SNPs found in this study in the 5' flanking region of ghrelin gene are the main determinants of ghrelin plasma levels. However, SNP-501 A>C genotype distribution seems to be different in subjects having the highest compared with those with the lowest ghrelin levels, and the SNP may be associated with BMI and waist circumference.
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PMID:Sequencing analysis of ghrelin gene 5' flanking region: relations between the sequence variants, fasting plasma total ghrelin concentrations, and body mass index. 1855 45

Ghrelin is an acylated 28-amino-acid peptide that stimulates food intake, GH secretion, and gastric motility. Experimental studies have suggested that ghrelin plays roles in glucose homeostasis, atherosclerosis, and microangiopathy. We investigated possible involvement of ghrelin in micro- and macro-vascular diabetic complications and glycemic control in diabetic patients. Fasting and postprandial plasma ghrelin concentrations after a test meal were measured in 108 and 61 Japanese diabetic patients, respectively. Plasma ghrelin concentrations were negatively correlated with body mass index (BMI) (r = -0.309, P = 0.002) or HbA(1c) (r = -0.264, P = 0.0065). Plasma ghrelin levels in patients with diabetic nephropathy who showed high serum creatinine levels (s-Cre) were significantly higher than those in patients who showed normal s-Cre (P<0.02). In patients with diabetic triopathy, plasma ghrelin concentrations were significantly lower than those in patients without diabetic complications (P<0.05). Stepwise multiple regression analyses revealed that s-Cre, BMI, and HbA(1c) were independently associated with plasma ghrelin levels. A postprandial decrease of ghrelin was observed in patients with normal CV(R-R) values or those with normal body weight, whereas it was not seen in obese patients or in patients with low CV (R-R) values. Suppression rates of ghrelin 30-60 min after a test meal in obese patients were significantly lower than those in normal-weight patients. These findings suggest that ghrelin secretion is suppressed by long-term hyperglycemia and that obesity influences the regulation of ghrelin secretion.
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PMID:Plasma ghrelin concentrations in different clinical stages of diabetic complications and glycemic control in Japanese diabetics. 1802 62

Ghrelin is a brain-gut peptide that serves as a natural ligand for growth hormone secretagogue receptor (GHSR). It also exists abundantly in the cardiovascular system. In order to evaluate the possible role of ghrelin in the development of atherosclerosis, the effect of ghrelin on the expression of cell differentiation antigen 40 (CD40) were studied. Human umbilical vein endothelial cell (HUVEC) line-ECV 304 was pre-treated with different concentrations of ghrelin, des-acyl ghrelin or [d-Lys]-GHRP-6 (a ghrelin receptor antagonist), and then induced with tumor necrosis factor-alpha (TNF-alpha) and interferon gamma (IFN-gamma). The mRNA levels of CD40 were analyzed by reverse transcription-polymerase chain reaction, and the expressions of CD40 protein in the cells were measured by flow cytometry (FCM) and Western blotting. The results showed that exogenous ghrelin could significantly inhibit TNF-alpha/IFN-gamma induced CD40 expression in HUVEC cells in a concentration-dependent manner. When treated with 1000 ng/ml of ghrelin, the mRNA level of CD40 in the cells was decreased by approximately 77%, but when treated with both 1000 ng/ml of ghrelin and 1000 ng/ml of [d-Lys]-GHRP-6, the mRNA level of CD40 in the cells was decreased by only 42%, suggesting that [d-Lys]-GHRP-6 could counteract the inhibitory effect of ghrelin in these cells. However, CD40 expression was not inhibited by des-acyl ghrelin at 1000 ng/ml. The results in protein expression analysis detected by FCM and Western blotting further confirmed these results. Our results suggested that in the cardiovascular system, ghrelin not only has an anti-inflammatory effect, but also has a significant immunoregulatory effect that may be mediated through the GHSR-1a receptor.
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PMID:Effect of exogenous ghrelin on cell differentiation antigen 40 expression in endothelial cells. 1806 90

Ghrelin plays an important role in regulation of feeding behavior and energy homeostasis. It stimulates the release of growth hormone (GH) from pituitary and also activates its receptors expressed e.g. in the heart, aorta and coronary arteries. Ghrelin besides its orexigenic influences also improves left ventricular function in men and rats. It inhibits both apoptosis and expression of proinflammatory cytokines by cardiomyocytes and endothelial cells. Based on the contemporary .literature we present the influence of ghrelin on cardiovascular diseases and atherosclerosis.
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PMID:[Ghrelin and its influence on cardiovascular system]. 1817 55

Since the discovery of Helicobacter pylori (H. pylori), numerous studies have considered the possibility that it plays a role in different extragastric diseases. Most of these studies may be classified as epidemiological studies or investigations of H. pylori eradication, but there are also case reports and in vitro studies. This review reveals the limitations common to most of them. Idiopathic thrombocytopenic purpura is the disease for which the strongest association with H. pylori infection has been shown. Data are also accumulating about the role of H. pylori infection in idiopathic iron deficiency anemia and chronic idiopathic urticaria. Interesting results show that H. pylori infection affects atherosclerosis and is weakly associated with ischemic heart disease and stroke. Moreover, CagA-positive H. pylori strains may play a role in the natural history of atherosclerotic stroke. Recent studies suggest a link between H. pylori and Parkinson's disease. Preliminary data indicate that H. pylori infection impairs gastric ghrelin production and may influence nutritional status. The association between H. pylori infection and other extragastric diseases remains controversial. H. pylori infection may cause extragastric manifestations directly or indirectly, by various mechanisms including atrophic gastritis, the release of inflammatory mediators, molecular mimicry, and systemic immune response. Evidence suggests that anti-H. pylori therapy improves idiopathic thrombocytopenic purpura (significant increase of platelet count in half of the cases), iron-deficiency anemia, and chronic urticaria (30% remission rate), but the data from randomized controlled trials are insufficient to confirm these positive effects.
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PMID:[Does Helicobacter pylori infection play a role in extragastric diseases?]. 1824 21


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